[go: up one dir, main page]

US20110305784A1 - Fractionated products obtained from gamboge resin, and medical uses of the same - Google Patents

Fractionated products obtained from gamboge resin, and medical uses of the same Download PDF

Info

Publication number
US20110305784A1
US20110305784A1 US13/068,730 US201113068730A US2011305784A1 US 20110305784 A1 US20110305784 A1 US 20110305784A1 US 201113068730 A US201113068730 A US 201113068730A US 2011305784 A1 US2011305784 A1 US 2011305784A1
Authority
US
United States
Prior art keywords
product
acid
tsb
correlated
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US13/068,730
Other languages
English (en)
Inventor
Sen-Bin Lee
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Taiwan Sunpan Biotechnology Development Co Ltd
Original Assignee
Taiwan Sunpan Biotechnology Development Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=44951548&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20110305784(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Taiwan Sunpan Biotechnology Development Co Ltd filed Critical Taiwan Sunpan Biotechnology Development Co Ltd
Assigned to TAIWAN SUNPAN BIOTECHNOLOGY DEVELOPMENT CO., LTD. reassignment TAIWAN SUNPAN BIOTECHNOLOGY DEVELOPMENT CO., LTD. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LEE, SEN-BIN
Publication of US20110305784A1 publication Critical patent/US20110305784A1/en
Priority to US14/964,309 priority Critical patent/US20160089357A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/38—Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings

Definitions

  • This invention relates to seventeen new compounds and five fractionated products obtained from an acetone-extracted product of gamboge resin.
  • the seventeen new compounds and the five fractionated products have been demonstrated to have activities in inhibiting the growth of tumor/cancer cells.
  • the acetone-extracted product of gamboge resin and the five fractionated products obtained therefrom have been demonstrated to have analgesic and anti-inflammatory effects. Therefore, this invention also relates to the use of said acetone-extracted product of gamboge resin, the five fractionated products thereof, and the seventeen new compounds in the preparation of pharmaceutical compositions.
  • Gamboge resin is the gum-resin secreted by the plant of Garcinia sp. of the family Guttiferae. It has been used as a source of vegetative dyes and pigments since the old days. It is also used in folk medicine in some areas such as India and Thailand.
  • Garcinia TungHUANG in pinyin
  • gamboge Garcinia morella Desv
  • Thailand G. harburyi Hook f.
  • the bark of the tree is cut open in a spiral shape about 2 meters from the ground to collect the exuding resin. The resin is then subjected to heat-drying to result in a solidified gamboge resin.
  • gamboge is effective in combating inflammations, clearing away toxins, stopping blood bleeding, and killing worms.
  • TCM Chinese medicine
  • gamboge resin many compounds can be isolated from extracts of gamboge resin, including: morellin, morellic acid, gambogic acid, morellinol, isomorellin, isomorellic acid, isogambogic acid, isomorellinol, neogambogic acid, desoxymorellin, dihydroisomorellin, ⁇ -guttiferin, ⁇ -guttiferin, gambogenic acid, desoxygambogenin, gambogellic acid, epigambogic acid, epiisogambogic acid, isogambogenic acid, 30-hydroxygambogic acid, etc.
  • Ming-Meia Jia et al. studied the chemical components of Garcinia hanburyi and isolated fifteen compounds from the cold ethanol-extracted product of Garcinia hanburyi via silica gel column chromatography (gradient elution solvent system: petroleum ether-acetone, acetone, methanol) and preparative HPLC.
  • the fifteen compounds were identified as 2 ⁇ -hydroxy-3 ⁇ -acetoxy-lup-20(29)-en-28-oic acid (1), 10 ⁇ -hydroxyepigambogic acid (2), gambogic acid (3), isogambogic acid (4), gambogin (5), gambogoic acid B (6), desoxymorellin (7), isomorellin (8), gambogenic acid (9), isogambogenin (10), gambogellic acid (11), desoxygambogenin (12), morellic acid (13), isomorellic acid (14), and 30-hydroxygambogic acid (15).
  • U.S. Pat. No. 7,138,428 B2 (corresponding to TW I282280 and CN 100413868 C) has disclosed an acetone-extracted product from gamboge resin, i.e., TSB-14.
  • nine compounds were further purified from said acetone-extracted product TSB-14, including a new compound formoxanthone A, and eight known compounds betulin, betulinic acid, morellic acid, isomorellic acid, gambogic acid, isogambogic acid, isomorellinol and desoxymorellin.
  • the acetone-extracted product TSB-14 and the nine purified compounds have been demonstrated to have effects in inhibiting the growth of tumor/cancer cells such as liver cancer cells (HepG2), lung cancer cells (A549), breast cancer cells (MCF-7), colon cancer cells (HT-29), leukemia cells (HL-60), and lymphoma cancer cells (U937).
  • tumor/cancer cells such as liver cancer cells (HepG2), lung cancer cells (A549), breast cancer cells (MCF-7), colon cancer cells (HT-29), leukemia cells (HL-60), and lymphoma cancer cells (U937).
  • TSB-14 acetone-extracted product from gamboge resin as disclosed in U.S. Pat. No. 7,138,428 B2, i.e., TSB-14, exhibits analgesic and anti-inflammatory activities.
  • the applicants further obtained seventeen new compounds and five fractionated products from the acetone-extracted product TSB-14 of gamboge resin, in which the seventeen new compounds have been demonstrated to have anti-cancer activity, and the five fractionated products have been demonstrated to have anti-cancer, analgesic and anti-inflammatory activities.
  • this invention provides a fractionated product of gamboge resin, which is prepared by a process comprising:
  • fractionated product is selected from the groups consisting of:
  • this invention provides a pharmaceutical composition comprising at least one of the fractionated products described above.
  • this invention provides an analgesic composition comprising at least one of the following:
  • this invention provides an anti-inflammatory composition comprising at least one of the following:
  • this invention provides an anti-cancer composition comprising at least one of the fractionated products described above.
  • this invention provides a method of inhibiting the growth of tumor/cancer cells, comprising contacting the cells with at least one of the fractionated products described above.
  • this invention provides a method of treating a cancer in a subject, comprising administering to the subject at least one of the fractionated products described above.
  • FIG. 1 shows the analytical RP-HPLC elution profile of an acetone-extracted product from gamboge resin, which is referred to as “TSB-14” hereinafter and which was prepared according to the method disclosed in Example 1 of U.S. Pat. No. 7,138,428 B2, in which peaks 1-35 respectively correspond to the thirty-five major components discovered during the retention time from 0 to 80 minutes;
  • FIG. 2 shows the elution profile of the product TSB-14 obtained from the semi-preparative RP-HPLC analysis conducted in section A, entitled “Semi-preparative RP-HPLC analysis of the product TSB-14,” of Example 2, infra, in which the observed peaks 1-35 correspond to those shown in of FIG. 1 , respectively;
  • FIG. 3 shows the semi-preparative RP-HPLC elution profile of fraction 1 obtained in section B, entitled “Preparation of fractions 1-3” of Example 2, infra, in which the observed twelve peaks correspond to peaks 1-12 shown in FIG. 2 , respectively;
  • FIG. 4 shows the semi-preparative RP-HPLC elution profile of fraction 2 obtained in Example 2, infra, in which the observed twelve peaks correspond to peaks 13-24 shown in FIG. 2 , respectively;
  • FIG. 5 shows the semi-preparative RP-HPLC elution profile of fraction 3 obtained in Example 2, infra, in which the observed eleven peaks correspond to peaks 25-35 shown in FIG. 2 , respectively;
  • FIG. 6 shows the elution profile of the product TSB-14 obtained from the semi-preparative RP-HPLC analysis conducted in section A, entitled “Semi-preparative RP-HPLC analysis of the product TSB-14,” of Example 4, infra;
  • FIG. 7 shows the semi-preparative RP-HPLC elution profile of a fractionated product TSB-14A obtained in Example 4, infra, in which the observed twelve peaks correspond to peaks 1-12 shown in FIG. 1 , respectively;
  • FIG. 8 shows the semi-preparative RP-HPLC elution profile of a fractionated product TSB-14B obtained in Example 4, infra, in which the observed three peaks correspond to peaks 13-15 shown in FIG. 1 , respectively;
  • FIG. 9 shows the semi-preparative RP-HPLC elution profile of a fractionated product TSB-14C obtained in Example 4, infra, in which the observed five peaks correspond to peaks 16-20 shown in FIG. 1 , respectively;
  • FIG. 10 shows the semi-preparative RP-HPLC elution profile of a fractionated product TSB-14D obtained in Example 4, infra, in which the observed four peaks correspond to peaks 21-24 shown in FIG. 1 , respectively;
  • FIG. 11 shows the semi-preparative RP-HPLC elution profile of a fractionated product TSB-14E obtained in Example 4, infra, in which the observed eleven peaks correspond to peaks 25-35 shown in FIG. 1 , respectively.
  • active component or “biologically active compound” is understood to include any substance or material, or combination of substances and materials, which is pharmacologically active and, hence, has therapeutic value.
  • fractionated product refers to a product obtained by subjecting a biological sample to a fractionation treatment (e.g., chromatography) so that two or more fractions from the biological sample are separated and collected.
  • a fractionation treatment e.g., chromatography
  • Example 1 of U.S. Pat. No. 7,138,428 B2 the applicants disclosed an acetone-extracted product from gamboge resin, i.e., TSB-14, which was obtained by pulverizing gamboge resin into powder, followed by extracting the pulverized powder with acetone.
  • the acetone-extracted product TSB-14 was further identified to contain formoxanthone A, betulin, betulinic acid, morellic acid, isomorellic acid, gambogic acid, isogambogic acid, isomorellinol, and desoxymorellin.
  • the applicants employed analytical RP-HPLC (reversed phase high performance liquid chromatography) and semi-preparative RP-HPLC analyses to isolate and purify any possible new biologically active compound(s) existing in the acetone-extracted product TSB-14, and to prepare biologically active fractionated products from the acetone-extracted product TSB-14.
  • analytical RP-HPLC reversed phase high performance liquid chromatography
  • semi-preparative RP-HPLC analyses to isolate and purify any possible new biologically active compound(s) existing in the acetone-extracted product TSB-14, and to prepare biologically active fractionated products from the acetone-extracted product TSB-14.
  • the acetone-extracted product TSB-14 was subjected to an analytical RP-HPLC analysis using an analytical RP-C8 column (Luna 3 ⁇ C8(2)). As shown in FIG. 1 , the obtained analytical RP-HPLC elution profile was observed to have 35 major peaks, which were designated as peaks 1 to 35, respectively.
  • the acetone-extracted product TSB-14 was then subjected to a semi-preparative RP-HPLC using a semi-preparative RP-C12 column (Synergi 4 ⁇ C12).
  • the obtained semi-preparative RP-HPLC elution profile as shown in FIG. 2 which was found to have 35 major peaks comparatively corresponding to those shown in FIG. 1 , was divided into three regions, in which Region 1 included peaks 1-12 discovered during the retention time from 0 to 42 minutes; Region 2 included peaks 13 to 24 discovered during the retention time from 42 to 135 minutes; and Region 3 includes peaks 25 to 35 discovered during the retention time from 135 to 280 minutes.
  • the acetone-extracted product TSB-14 was fractionated by semi-preparative RP-HPLC to provide three eluates that respectively corresponded to said three divided regions.
  • the three eluates thus collected were respectively subjected to the following treatment: partitioning a collected eluate in H 2 O and ethyl acetate; after washing with H 2 O so as to remove TFA, the organic layer was dried on anhydrous Na 2 SO 4 , filtered, and the organic solvent was removed using a vacuum rotatory evaporator.
  • Three corresponding fractions 1-3 thus obtained were separately subjected to the semi-preparative RP-HPLC analysis to provide elution profiles as shown in FIGS. 3 , 4 and 5 , which were observed to have peaks 1-12, 13-24 and 25-35, respectively.
  • the obtained fraction 1 was subjected to the semi-preparative RP-HPLC analysis and, according to its elution profile shown in FIG. 3 , twelve eulates that respectively corresponded to peaks 1-12 shown in FIG. 3 were collected.
  • the collected eluates 1-12 were then subjected to the following treatment: partitioning a collected eluate in H 2 O and ethyl acetate; after washing with H 2 O so as to remove TFA, the organic layer was dried on anhydrous Na 2 SO 4 , filtered, and the organic solvent was removed using a vacuum rotatory evaporator. Twelve crude products were obtained, each of which was further purified.
  • Fraction 2 was treated in a manner identical to fraction 1, and according to its elution profile shown in FIG. 4 , eluates 13-24 that respectively corresponded to peaks 13-24 shown in FIG. 4 were collected, and twelve purified products were further obtained from the eluates 13-24 of fraction 2 and were designated as Gh-47, Gh-4602, Gh-4601, Gh-1601-A, Gh-1050, Gh-1602, Gh-1631, Gh-2641-1, Gh-2501, Gh-2642, Gh-2507 and Gh-2505, respectively (see Table 2 of Example 2, infra).
  • Fraction 3 was likewise treated in a manner identical to fraction 1, and according to its elution profile shown in FIG. 5 , eluates 25-35 that respectively corresponded to peaks 25-35 shown in FIG. 5 were collected, and eleven purified products were further obtained from the eluates 25-35 of fraction 3 and were designated as Gh-2508, Gh-2603-1, Gh-2603-2, Gh-1641, Gh-1642, Gh-2605, Gh-2606, Gh-2607-B, Gh-2607-1A, Gh-2301 and Gh-4301, respectively (see Table 3 of Example 2, infra)
  • the thirty-five products purified from fractions 1-3 were subjected to physical and chemical analyses, including melting point determination, nuclear magnetic resonance (NMR) spectroscopy (e.g., 1 H-NMR and 13 C-NMR spectroscopy), mass spectrometry (e.g., electron impact mass spectrometry (EIMS), high-resolution electron impact mass spectrometry (HREIMS), fast atom bombardment mass spectrometry (FABMS), and high-resolution fast atom bombardment mass spectrometry (HRFABMS), etc.), etc.
  • NMR nuclear magnetic resonance
  • HREIMS high-resolution electron impact mass spectrometry
  • FABMS fast atom bombardment mass spectrometry
  • HRFABMS high-resolution fast atom bombardment mass spectrometry
  • Product Gh-631 has been confirmed by chemical structure analysis to be a known compound, i.e., “formoxanthone A” disclosed in U.S. Pat. No. 7,138,428 B2, which has the following chemical structure:
  • Product Gh-4601 has been confirmed by chemical structure analysis to be a known derivative of isomorellic acid, i.e., isomorellinol, which has the following chemical structure:
  • Product Gh-2641-1 has been confirmed by chemical structure analysis to be neogambogic acid, which has the following chemical structure:
  • Product Gh-2501 has been confirmed by chemical structure analysis to be isomorellin, which has the following chemical structure:
  • Product Gh-2301 has been confirmed by chemical structure analysis to be a known compound, i.e., desoxymorellin, which has the following chemical structure:
  • Product Gh-4301 has been confirmed by chemical structure analysis to be a known compound, i.e., desoxygambogenin, which has the following chemical structure:
  • product Gh-3272 is a novel compound which is hitherto not reported.
  • Product Gh-3272 is herein named as “formoxanthone H” and has the following chemical structure:
  • product Gh-3332 is a novel compound which is hitherto not reported.
  • Product Gh-3332 is herein named as “isoformoxanthone I” and has the following chemical structure:
  • product Gh-3291 is a novel compound which is hitherto not reported.
  • Product Gh-3291 is herein named as “formoxanthone D” and has the following chemical structure:
  • product Gh-1631 is a novel compound which is hitherto not reported.
  • Product Gh-1631 is herein named as “formoxanthone C” and has the following chemical structure:
  • product Gh-1050 is a novel compound which is hitherto not reported.
  • Product Gh-1050 is herein named as “3 ⁇ -hydroxygambogellic acid” and has the following chemical structure:
  • R 1 and R 2 together form a moiety selected from the group consisting of:
  • R 3 is selected from the group consisting of: 3-methyl-2-butenyl, 1-hydroxy-2,3-epoxy-3-methylbutyl, 2,3-epoxy-3-methylbutyl, and 2,3-dihydroxy-3-methylbutyl;
  • R 4 is selected from the group consisting of: 3-carboxyl-2Z-butenyl, 3-carboxyl-2E-butenyl, 3-carboxyl-1E-butenyl; but excluding compounds of the following formulae:
  • the seventeen new compounds obtained in this invention may be chemically synthesized by methodologies well known to those skilled in the art.
  • the acetone-extracted product TSB-14 was further subjected to a semi-preparative RP-HPLC analysis performed under different elution conditions so that an elution profile as shown in FIG. 6 was obtained.
  • the elution profile of FIG. 6 was then divided into five regions, in which region A corresponded to the retention times from 0 to 13.7 minutes; region B corresponded to the retention times from 13.7 to 20.4 minutes; region C corresponded to the retention times from 20.4 to 26.1 minutes; region D corresponded to the retention times from 26.1 to 34.9 minutes; and region E corresponded to the retention times from 34.9 to 53.8 minutes.
  • the acetone-extracted product TSB-14 was fractionated by semi-preparative RP-HPLC to provide five eluates that corresponded to the five divided regions A-E, respectively.
  • the five eluates A-E thus collected were respectively subjected to the following treatment: partitioning a collected eluate in H 2 O and ethyl acetate; after washing with H 2 O so as to remove TFA, the organic layer was dried on anhydrous Na 2 SO 4 , filtered, and the organic solvent was removed using a vacuum rotatory evaporator.
  • the fractioned products TSB-14A, TSB-14B, TSB-14C, TSB-14D, and TSB-14E were found to contain peaks that corresponded to peaks 1-12, peaks 13-15, peaks 16-20, peaks 21-24, and peaks 25-35 shown in FIG.
  • fractionated product TSB-14A contains Products Gh-3261, Gh-3271, Gh-3272, Gh-3311, Gh-3332, Gh-1036, Gh-3291, Gh-631, Gh-1052, Gh-3351, Gh-3353 and Gh-3352;
  • the fractionated product TSB-14B contains Products Gh-47, Gh-4602 and Gh-4601;
  • the fractionated product TSB-14C contains Products Gh-1601-A, Gh-1050, Gh-1602, Gh-1631 and Gh-2641-1;
  • the fractionated product TSB-14D contains Products Gh-2501, Gh-2642, Gh-2507 and Gh-2505;
  • fractionated product TSB-14E contains Products Gh-2508, Gh-2603-1, Gh-2603-2, Gh-1641, Gh-1642, Gh-2605, Gh-2606, Gh-2607-B, Gh-2607-1A, Gh-2
  • the seventeen new purified compounds and the five fractioned products TSB-14A to TSB-14E obtained from the acetone-extracted product TSB-14 from gamboge resin were subjected to in vitro anti-cancer tests and were found to exhibit inhibitory activities against the growth of tumor/cancer cells (such as human breast adenocarcinoma cells, human colon adenocarcinoma cells, human promyelocytic leukemia cells, human hepatocellular carcinoma cells, human lung carcinoma cells, and human histocytic lymphoma cells).
  • tumor/cancer cells such as human breast adenocarcinoma cells, human colon adenocarcinoma cells, human promyelocytic leukemia cells, human hepatocellular carcinoma cells, human lung carcinoma cells, and human histocytic lymphoma cells.
  • acetone-extracted product TSB-14 and the five fractionated products TSB-14A to TSB-14E obtained therefrom were further tested for their activities and binding abilities to nine cancer-related proteins, including: cyclooxygenase-2 (COX-2); protein serine/threonine kinases AURKB (Aurora-B kinase) and CDC2/CCNB1 (cdkl/cyclin B); protein tyrosine kinases ABL1 (ABL), epidermal growth factor receptor (EGFR), ERBB2 (HER2), insulin receptor and KDR (VEGFR-2).
  • COX-2 cyclooxygenase-2
  • AURKB Aurora-B kinase
  • CDC2/CCNB1 cdkl/cyclin B
  • the obtained results show that the acetone-extracted product TSB-14 and the five fractionated products TSB-14A to TSB-14E obtained therefrom exhibit a significant inhibitory activity upon the tested cancer-related proteins.
  • the nine tested cancer-related proteins are known to be associated with various tumors/cancers (e.g., colorectal cancer, gastric cancer, non-small cell lung cancer, brain cancer, thyroid cancer, nasopharyngral cancer, chronic myelocytic leukemia, T-cell acute lymphoblastic leukemia, lung cancer, colon cancer, breast cancer, leukemia, liver cancer, ovarial cancer, renal cancer, pancreas cancer, and endometrial cancer), it is contemplated that the acetone-extracted product TSB-14 and the five fractionated products TSB-14A to TSB-14E obtained therefrom can be used in the treatment of tumors/cancers.
  • tumors/cancers e.g., colorectal cancer, gastric cancer, non-small cell lung cancer
  • this invention provides a compound purified from gamboge resin and selected from the group consisting of:
  • This invention also provides a fractionated product of gamboge resin, which is prepared by a process comprising:
  • fractionated product is selected from the groups consisting of:
  • This invention further provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound as described above, a fractionated product as described above, or a combination thereof.
  • This invention also provides a method of inhibiting the growth of tumor/cancer cells, comprising contacting the cells with a compound as described above, a fractionated product as described above, or a combination thereof.
  • this invention further provides an anti-cancer composition comprising at least one of the following:
  • This invention also provides a method of treating a cancer in a subject, comprising administering to the subject at least one of the following:
  • the acetone-extracted product TSB-14 and the five fractionated products TSB-14A to TSB-14E obtained therefrom were further found to have analgesic and anti-inflammatory effects.
  • an analgesic composition comprising at least one of the following:
  • This invention also provides an anti-inflammatory composition comprising at least one of the following:
  • composition according to this invention can be formulated into a dosage form suitable for parenteral, topical, or oral administration using technology well known to those skilled in the art, which includes, but is not limited to, injections (e.g., sterile aqueous solutions or dispersions), sterile powder, tablets, troches, pills, capsules, and the like.
  • injections e.g., sterile aqueous solutions or dispersions
  • sterile powder e.g., sterile powder, tablets, troches, pills, capsules, and the like.
  • the pharmaceutical composition according to this invention can be parenterally administered via at least one of the following routes: intravenous injection, intramuscular injection, and subcutaneous injection.
  • the pharmaceutical composition is formulated into a dosage form suitable for oral administration.
  • the pharmaceutical composition according to this invention can additionally comprise a pharmaceutically acceptable carrier widely employed in the art of drug-manufacturing.
  • the pharmaceutically acceptable carrier may include one or more of the following agents: solvents, emulsifiers, suspending agents, decomposers, binding agents, excipients, stabilizing agents, chelating agents, diluents, gelling agents, preservatives, lubricants, absorption delaying agents, plasticizer, filling agents, disintegrants, surfactants, thickening agents, liposomes, and the like.
  • the dosage and the frequency of administration of the pharmaceutical composition according to this invention may vary depending on the following factors: the severity of the disease to be treated, the route of administration, and the weight, age, physical condition and response of the subject to be treated.
  • the daily dosage of the pharmaceutical composition according to this invention may be 2.1 to 3.0 mg per kilogram of the body weight, and may be administered in a single dose or in several doses.
  • Melting point was determined using a micro melting-point apparatus (Yanaco, Japan).
  • EIMS spectra and HREIMS spectra were recorded on a MAT-95 XL high-resolution mass spectrometer.
  • FABMS spectra and HRFABMS spectra were recorded on a JEOL JMSSX SX 102A mass spectrometer or a Finnigan MAT 95 XL mass spectrometer.
  • RP-HPLC reversed-phase high performance liquid chromatography
  • Operation conditions for analytical RP-HPLC were as follows: a sample injection volume of 5 ⁇ L; mobile phase: 0.05% trifluoroacetic acid (TFA) (aq.) /100% acetonitrile (35:65, v/v); column flow rate: 0.75 mL/min; column oven temperature: 35° C.; and detection wavelength: 360 nm.
  • TFA trifluoroacetic acid
  • RP-HPLC Semi-preparative RP-HPLC was performed using the following instruments: a Hitachi L-7400 UV detector, a Hitachi L-7150 pump, a Hitachi HPLC D-7000 system, a column oven (Super CO-150, Enshine, Taiwan), a guard column (SecurityGuard Cartridge C12, size: 10 mm ⁇ 10 mm, Phenomenex, USA), and an analytical column (Synergi 4 ⁇ C12 80 ⁇ , size: 10 mm ⁇ 150 mm, Phenomenex, USA).
  • Operation conditions for semi-preparative RP-HPLC were as follows: a sample injection volume of 250 ⁇ L; mobile phase, which was selected depending on experiment; gradient elution, which was selected depending on experiment; column flow rate: 4.5 mL/min; column oven temperature: 27° C.; and detection wavelength: 360 nm.
  • 35 major peaks (numbered from 1 to 35) are present in the elution profile of the product TSB-14 within the retention time of 0 to 80 minutes. According to the results shown in FIG. 1 , the applicants postulated that it might be possible to isolate 35 compounds from the product TSB-14. To verify this postulation, the product TSB-14 was subjected to the following experiments.
  • Region 1 which includes peaks 1-12 eluted at a retention time of 0 to 42 minutes
  • Region 2 which includes peaks 13 to 24 eluted at a retention time of 42 to 135 minutes
  • Region 3 which includes peaks 25 to 35 eluted at a retention time of 135 to 280 minutes.
  • 3 g of the product TSB-14 was subjected to a semi-preparative RP-HPLC analysis as described in the preceding section A, and three eluates that respectively correspond to Regions 1, 2 and 3 of the elution profile shown in FIG. 2 were collected and then respectively subjected to the following treatment: partitioning a collected eluate in H 2 O and ethyl acetate; after washing with H 2 O so as to remove TFA, the organic layer was dried on anhydrous Na 2 SO 4 , filtered, and the organic solvent was removed using a vacuum rotatory evaporator.
  • fraction 1 as obtained in the preceding section B 100 mg was dissolved in 1 mL of acetone, followed by subjecting to a semi-preparative RP-HPLC analysis as described in the preceding section A, in which eluates 1-12 that respectively correspond to the elution peaks 1-12 in the semi-preparative RP-HPLC elution profile of fraction 1 as shown in FIG. 3 , were collected.
  • fraction 2 as obtained in the preceding section B 100 mg was dissolved in 1 mL of acetone, followed by subjecting to a semi-preparative RP-HPLC analysis as described in the preceding section A, in which eluates 13-24 that respectively correspond to the elution peaks 13-24 in the semi-preparative RP-HPLC elution profile of fraction 2 as shown in FIG. 4 , were collected.
  • fraction 3 as obtained in the preceding section B 100 mg was dissolved in 1 mL of acetone, followed by subjecting to a semi-preparative RP-HPLC analysis as described in the preceding section A, in which eluates 25-35 that respectively correspond to the elution peaks 25-35 in the semi-preparative RP-HPLC elution profile of fraction 3 as shown in FIG. 5 , were collected.
  • EIMS m/z (relative intensity): 560 [M] + (100), 545 (47), 532 (22), 517 (36), 405 (44), 389 (11), 363 (24), 349 (17), 307 (12), 287 (22), 285 (16), 245 (15), 215 (12), 189 (5).
  • product Gh-47 was identified to be a known compound having the following chemical structure, i.e., isomorellic acid:
  • product Gh-631 was identified to be a known compound having the following chemical structure, i.e., formoxanthone A:
  • EIMS m/z (relative intensity): 546 [M] + (100), 531 (18), 518 (44), 503 (40), 485 (9), 433 (7), 405 (33), 391 (10), 363 (19), 349 (13), 307 (10), 287 (25), 245 (8), 231 (18), 214 (12), 189 (5), 105 (6).
  • product Gh-4601 was identified to be a known compound having the following chemical structure, i.e., isomorellinol:
  • EIMS m/z (relative intensity): 560 [M] + (100), 545 (56), 532 (63), 517 (48), 487 (12), 433 (9), 405 (81), 391 (22), 363 (38), 349 (24), 307 (18), 287 (64), 245 (40), 231 (21), 215 (20), 189 (10).
  • product Gh-4602 was identified to be a known compound having the following chemical structure, i.e., morellic acid:
  • EIMS m/z (relative intensity): 530 [M] + (100), 515 (22), 502 (92), 488 (30), 487 (83), 459 (11), 433 (20), 405 (49), 391 (15), 363 (24), 349 (16), 307 (13), 287 (27), 231 (13), 215 (37), 189 (6).
  • product Gh-2301 was identified to be a known compound having the following chemical structure, i.e., desoxymorellin:
  • EIMS m/z (relative intensity): 600 [M] + (100), 572 (77), 557 (21), 531 (10), 503 (60), 475 (26), 449 (33), 393 (9), 357 (12), 351 (26), 323 (9), 309 (16), 295 (45), 281 (12), 253 (53), 231 (18), 215 (40), 189 (10), 177 (18), 173 (12), 69 (65).
  • product Gh-4301 was identified to be a known compound having the following chemical structure, i.e., desoxygambogenin:
  • product Gh-2605 was identified to be a known compound having the following chemical structure, i.e., gambogic acid:
  • EIMS m/z (relative intensity): 628 [M] + (24), 600 (11), 545 (100), 517 (21), 473 (12), 431 (4), 389 (8), 347 (6), 245 (7), 215 (14), 189 (5), 69 (4).
  • product Gh-2606 was identified to be a known compound having the following chemical structure, i.e., epigambogic acid:
  • EIMS m/z (relative intensity): 628 [M] + (32), 600 (6), 545 (100), 517 (12), 473 (6), 431 (2), 389 (4), 355 (5), 245 (8), 215 (11), 189 (3), 69 (5).
  • product Gh-1641 was identified to be a known compound having the following chemical structure, i.e., isogambogic acid:
  • product Gh-1642 was identified to be a known compound having the following chemical structure, i.e., epiisogambogic acid:
  • EIMS m/z (relative intensity): 628 [M] + (92), 600 (91), 545 (54), 517 (46), 474 (100), 473 (88), 459 (18), 431 (29), 417 (15), 391 (33), 355 (37), 349 (25), 295 (18), 253 (21), 245 (25), 215 (30), 189 (18), 69 (20).
  • the EIMS data of Product Gh-2603-2 show a molecular ion peak [M] + at m/z 628, which is identical to that observed in gambogic acid.
  • the NOESY data of Product Gh-2603-2 also reveal that ⁇ 7.47 (H-10) was correlated with ⁇ 3.43 (H-11); ⁇ 3.43 (H-11) was correlated with ⁇ 2.28 (H 1 -21); ⁇ 1.33 (H 2 -21) was correlated with ⁇ 2.51 (H-22); ⁇ 2.28 (H 1 -21) was correlated with ⁇ 2.51 (H-22) and ⁇ 1.27 (H-24); and ⁇ 6.00 (H-27) was correlated with ⁇ 1.68 (H-29), evidencing that the stereostructure of Product Gh-2603-2 in this part is identical to that of gambogic acid.
  • the stereostructure of Product Gh-2603-2 in this part has a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • the monoterpene moiety of Product Gh-2603-2 was determined to have a rigid chair conformation, in which an 1,3-diaxial interaction exists amongst H-37, H-3, and H-20; the methyl proton (H-19) attached to C-2 and the isopropenyl group attached to C-37 were in an equatorial orientation, so that the stereostructure of Product Gh-2603-2 in this part has a 2R,4R,37S configuration.
  • Product Gh-2603-2 was identified to be a known compound having the following chemical structure, i.e., gambogellic acid:
  • EIMS m/z (relative intensity): 628 [M] + (92), 600 (100), 545 (68), 517 (49), 474 (98), 473 (80), 459 (17), 431 (25), 417 (13), 391 (28), 355 (24), 349 (18), 295 (11), 253 (12), 245 (13), 215 (16), 189 (7), 69 (15).
  • the EIMS data of product Gh-2603-1 show a molecular ion peak [M] + at m/z 628, which reveals that the fragmentation pattern of Product Gh-2603-1 is identical to that of Product Gh-2603-2 (i.e., gambogellic acid). Besides, the 1 H-NMR and 13 C-NMR data of Product Gh-2603-1 are generally similar to those of Product Gh-2603-2.
  • the methylene group (C-26) is capable of free rotation. If C-2 is in a S configuration, the monoterpene p-menthene ring and the isopropenyl group containing C-2 form a steric hindrance to free rotation, thereby resulting in a nonequivalence of the two protons in the methylene group, as well as an anisotropic effect to relevant protons.
  • the HMBC data of Product Gh-2603-1 also show that: H-3 is correlated with C-5 in the aromatic ring, and both the isopropenyl group attached to C-37 and the methyl proton (H-19) attached to C-2 are in an equatorial orientation. Therefore, the monoterpene moiety has a rigid chair conformation.
  • NOESY data of Product Gh-2603-1 also shows that: ⁇ 7.48 (H-10) is correlated with ⁇ 3.44 (H-11); ⁇ 3.44 (H-11) is correlated with ⁇ 2.29 (H 1 -21); ⁇ 1.34 (H 2 -21) is correlated with ⁇ 2.46 (H-22); both ⁇ 2.29 (H 1 -21) and ⁇ 2.46 (H-22) are correlated with ⁇ 1.27 (H-24); and ⁇ 5.99 (H-27) is correlated with ⁇ 1.69 (H-29).
  • Product Gh-2603-1 was identified to be a known compound having the following chemical structure, i.e., “epigambogellic acid” ⁇ IUPAC nomemclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,9S,10R,13S,16aS)-3a,4,5,7,10,11,12,13-octahydro-8-hydroxy-3,3,13-trimethyl-[5-(3-methyl-2-butenyl)-10-(1-methylethenyl)-7,18-dioxo-1,5:9,13-dimethano-1H,3H,9H-furo[3.4-g]oxocino[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ :
  • EIMS m/z (relative intensity): 628 [M] + (33), 600 (17), 545 (100), 517 (23), 499 (4), 474 (14), 431 (5), 389 (8), 355 (7), 347 (6), 245 (5), 215 (9), 189 (3), 69 (4); HREIMS [M] + m/z: 628.3034; calculated for C 38 H 44 O 8 , 628.3036.
  • the EIMS data of Product Gh-2607-B show a molecular ion peak [M] + at m/z 628 and the HREIMS data of Product Gh-2607-B show a molecular ion peak [M] + at m/z 628.3034, indicating that Product Gh-2607-B has a molecular formula identical to those of the above-described compounds gambogic acid and gambogellic acid as well as their epimers, i.e., C 38 H 44 O 8 .
  • Product Gh-2607-B is structurally similar to gambogellic acid except for at the monoterpene moiety. As compared to gambogellic acid, Product Gh-2607-B was found to have one less double bond. Product Gh-2607-B was therefore presumed to have one more ring than gambogellic acid.
  • the methine group (C-3) of Product Gh-2607-B is a transformation of the methylene group (C-3) of gambogellic acid, and said transformation is presumed to be caused by forming a bond between C-3 and C-38 to replace a terminal double bond between C-38 and C-40, thereby resulting in the formation of a pinane-type monoterpene structure, which includes a cyclobutane, a gem-dimethyl group (C-39 ( ⁇ 17.68) and C-40 ( ⁇ 33.45)), an oxygen-bearing quaternary carbon (C-2 ( ⁇ 85.18)), and a tertiary methyl group (C-19 ( ⁇ 27.35)) attached to the oxygen-bearing quaternary carbon.
  • HMBC data of Product Gh-2607-B show that: in addition to being correlated with an aromatic carbon ⁇ 105.32 (C-5), ⁇ 161.17 (C-6) and ⁇ 161.53 (C-18), ⁇ 2.95 (H-3) is correlated with ⁇ 85.18 (C-2), ⁇ 46.23 (C-37), ⁇ 38.81 (C-38), ⁇ 38.58 (C-20), ⁇ 36.93 (C-4), ⁇ 33.45 (C-40), and ⁇ 17.68 (C-39); ⁇ 2.42 (H-4) is correlated with ⁇ 105.32 (C-5), ⁇ 85.18 (C-2), ⁇ 38.81 (C-38), ⁇ 35.01 (C-3), ⁇ 27.35 (C-19) and ⁇ 25.61 (C-36); and ⁇ 2.31 (H-37) is correlated with ⁇ 85.18 (C-2), ⁇ 38.81 (C-38), ⁇ 35.01 (C-3), ⁇ 36.93 (C-4),
  • the NOESY data of Product Gh-2607-B also reveal that: ⁇ 7.50 (H-10) is correlated with ⁇ 3.46 (H-11); ⁇ 3.46 (H-11) is correlated with ⁇ 2.29 (H 1 -21); ⁇ 1.36 (H 2 -21) is correlated with ⁇ 2.50 (H-22); and ⁇ 2.50 (H-22) is correlated with ⁇ 1.69 (H-25), evidencing that the stereostructure of Product Gh-2607-B in this part has a 11S,13R,14S,22S configuration, which includes H-27 and a carboxyl group (C-30) in a trans-relationship inasmuch as ⁇ 1.67 (H-29) is correlated with ⁇ 5.86 (H-27), and a double bond ⁇ 27,28 in a Z configuration.
  • Product Gh-2607-B is identified to be a new compound having the following chemical structure:
  • Product Gh-2607-B is identified by the name “formoxanthone B” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,9S,10S,12R,15R,18aS)-3a,4,5,7,12,13,14,15-octahydro-8-hydroxy-3,3,11,11,15-pentamethyl-17-(3-methyl-2-butenyl)-7,19-dioxo-1,5-methano-1H,3H,9H-furo[3.4-g]-16-oxa-tricyclo[4.4.0.0 9,12 ]decano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 628 [M] + (27), 601 (13), 545 (100), 517 (20), 473 (12), 389 (8), 355 (7), 347 (7), 245 (10), 215 (18), 189 (8), 69 (11); HREIMS [M + ] m/z: 628.3046; calculated for C 38 H 44 O 8 , 628.3036.
  • the EIMS data of Product Gh-2607-1A show a molecular ion peak [M] + at m/z 628 and the HREIMS data of Product Gh-2607-1A show a molecular ion peak [M] + at m/z 628.3046, indicating that Product Gh-2607-1A has a molecular formula identical to those of the above-described compounds gambogic acid and gambogellic acid as well as their epimers, C 38 H 44 O 8 .
  • Product Gh-2607-1A is structurally similar to gambogellic acid except for at the monoterpene moiety. As compared to gambogellic acid, Product Gh-2607-1A was found to have one less double bond. Product Gh-2607-1A was therefore presumed to have one more ring than gambogellic acid.
  • the methine group (C-3) of Product Gh-2607-1A is a transformation of the methylene group (C-3) of gambogellic acid, and said transformation is presumed to be caused by forming a bond between C-3 and C-38 to replace a terminal double bond between C-38 and C-40, thereby resulting in the formation of a pinane-type monoterpene structure, which includes a cyclobutane, a gem-dimethyl group (C-39 ( ⁇ 17.65) and C-40 ( ⁇ 33.41)), an oxygen-bearing quaternary carbon (C-2 ( ⁇ 85.12)), and a tertiary methyl group (C-19 ( ⁇ 27.31)) attached to the oxygen-bearing quaternary carbon.
  • HMBC data of Product Gh-2607-1A show that: in addition to being correlated with aromatic ring carbons ⁇ 105.28 (C-5), ⁇ 161.15 (C-6) and ⁇ 161.51 (C-18), ⁇ 2.93 (H-3) is correlated with ⁇ 85.12 (C-2), ⁇ 46.19 (C-37), ⁇ 38.77 (C-38), ⁇ 38.53 (C-20), ⁇ 36.90 (C-4), ⁇ 33.41 (C-40) and ⁇ 17.65 (C-39); ⁇ 2.40 (H-4) is correlated with ⁇ 105.28 (C-5), ⁇ 38.77 (C-38), ⁇ 34.97 (C-3), ⁇ 46.19 (C-37), ⁇ 25.59 (C-36), ⁇ 38.53 (C-20) and ⁇ 27.31 (C-19); and ⁇ 2.30 (H-37) is correlated with ⁇ 105.28 (C-5), ⁇ 85.12 (C-2), ⁇ 38.77 (
  • the NOESY data of Product Gh-2607-1A show that: ⁇ 7.49 (H-10) is correlated with ⁇ 3.46 (H-11); ⁇ 3.46 (H-11) is correlated with ⁇ 2.28 (H 1 -21); ⁇ 1.35 (H 2 -21) is correlated with ⁇ 2.49 (H-22); ⁇ 2.49 (H-22) is correlated with ⁇ 1.68 (H-25); and ⁇ 5.87 (H-27) is correlated with ⁇ 1.66 (H-29), evidencing that the stereostructure of Product Gh-2607-1A in this part has a 11S,13R,14S,22S configuration, which includes H-27 and a carboxyl group (C-30) in a trans-relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • ⁇ 2.93 (H-3) is correlated with ⁇ 2.40 (H-4), ⁇ 1.28 (H-19) and ⁇ 1.27 (H-40);
  • ⁇ 2.40 (H-4) is correlated with ⁇ 2.30 (H-37), ⁇ 1.27 (H-40) and ⁇ 1.66 (H-29);
  • ⁇ 2.30 (H-37) is correlated with ⁇ 1.66 (H-29) and ⁇ 1.70 (H-34); and
  • ⁇ 1.50 (H 2 -36) is correlated with ⁇ 1.66 (H-29).
  • C-2 is in a S configuration; and in the pinane structure, the three methine protons H-3, H-4 and H-37 in the cyclobutane ring are in cis-relationship such that the cyclobutane ring is in a 3S,4S,37R configuration.
  • Product Gh-2607-1A is identified to be a new compound having the following chemical structure:
  • Product Gh-2607-1A is identified by the name “epiformoxanthone B” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,9R,10R,12S,15S,18aS)-3a,4,5,7,12,13,14,15-octahydro-8-hydroxy-3,3,11,11,15-pentamethyl-17-(3-methyl-2-butenyl)-7,19-dioxo-1,5-methano-1H,3H,9H-furo[3.4-g]-16-oxa-tricyclo[4.4.0.0 9,12 ]decano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 628 [M] + (71), 600 (100), 575 (14), 545 (52), 517 (68), 501 (12), 473 (96), 459 (12), 431 (26), 417 (18), 389 (29), 355 (64), 349 (26), 307 (12), 295 (22), 253 (24), 245 (29), 214.9 (26), 189 (17), 105 (15), 91 (18), 69 (35).
  • the EIMS data of Product Gh-2508 show a molecular ion peak [M] + at m/z 628, which reveals that the fragmentation pattern of Product Gh-2508 is identical to that of Product Gh-2603-2 (i.e., gambogellic acid). Besides, the 1 H-NMR and 13 C-NMR data of Product Gh-2508 are generally similar to those of Product Gh-2603-2.
  • a methine group ( ⁇ 2.90 (H-28) and ⁇ 41.74 (C-28)) is adjacent to a carboxyl carbon ( ⁇ 177.35 (C-30)), indicating that the carboxyl carbon is not an ⁇ , ⁇ -unsaturated carbonyl carbon.
  • the HMBC data of Product Gh-2508 show that: ⁇ 5.79 (H-27) is correlated with ⁇ 177.35 (C-30), ⁇ 15.80 (C-29), ⁇ 41.74 (C-28) and ⁇ 84.76 (C-13); ⁇ 5.30 (H-26) is correlated with ⁇ 177.35 (C-30), ⁇ 41.74 (C-28), ⁇ 134.33 (C-27) and ⁇ 84.76 (C-13); ⁇ 2.90 (H-28) is correlated with ⁇ 177.35 (C-30), ⁇ 15.80 (C-29), ⁇ 134.33 (C-27) and ⁇ 123.80 (C-26); and ⁇ 0.90 (H-29) is correlated with ⁇ 177.35 (C-30) and ⁇ 134.33 (C-27), evidencing that the side chain connected to C-13 is (E)-2-methyl-3-butenoic acid.
  • the NOESY data of Product Gh-2508 show that ⁇ 7.50 (H-10) is correlated with ⁇ 3.43 (H-11); ⁇ 3.43 (H-11) is correlated with ⁇ 2.29 (H 1 -21); and ⁇ 2.56 (H-22) is correlated with ⁇ 1.42 (H 2 -21) and ⁇ 1.27 (H-24), evidencing that the stereostructure of Product Gh-2508 in this part is identical to that of gambogic acid or gambogellic acid, i.e., in a 11S,13R,14S,22S configuration. Besides, ⁇ 0.90 (H-29) is correlated with not only ⁇ 5.79 (H-27) and ⁇ 5.30 (H-26) but also the adjacent ⁇ 2.90 (H-28).
  • the NOESY data of Product Gh-2508 show that: ⁇ 3.50 (H-4) is correlated with not only ⁇ 2.16 (H-37) but also ⁇ 1.89 (H 1 -3) and ⁇ 1.75 (H 2 -3); ⁇ 1.89 (H 1 -3) is correlated with ⁇ 1.38 (H-19); and an axial hydrogen ⁇ 2.16 (H-37) is correlated with ⁇ 1.89 (H 1 -3) and ⁇ 1.56 (H 2 -20), evidencing that the monoterpene ring has a chair conformation with 1,3-diaxial interaction, and both the methyl proton (H-19) connected to C-2 and the isopropenyl group connected to C-37 are in an equatorial orientation.
  • Product Gh-2508 is identified to be a new compound having the following chemical structure:
  • Product Gh-2508 is identified by the name “ ⁇ -gambogellic acid” ⁇ IUPAC nomenclature: [3-butenoic acid, 2-methyl-4-[(1R,3aS,5S,9R,10S,13R,16aS)-3a,4,5,7,10,11,12,13-octahydro-8-hydroxy-3,3,13-trimethyl-[5-(3-methyl-2-butenyl)-10-(1-methylethenyl)-7,18-dioxo-1,5:9,13-dimethano-1H,3H,9H-furo[3.4-g]oxocino[3.2-b]xanthen-1-yl]-,(3E)-] ⁇ .
  • EIMS m/z (relative intensity): 628 [M] + (48), 600 (100), 585 (9), 545 (41), 517 (69), 510 (12), 473 (93), 431 (24), 417 (18), 389 (28), 355 (68), 347 (25), 307 (11), 299 (24), 295 (20), 253 (22), 245 (28), 214.9 (22), 199 (18), 189 (15), 105 (12), 91 (17), 69 (25).
  • the EIMS data of Product Gh-2507 show a molecular ion peak [M] + at m/z 628, which is identical to those of Products Gh-2603-1 (i.e., epigambogellic acid) and Gh-2603-2 (i.e., gambogellic acid). Besides, the 1 H-NMR and 13 C-NMR data of Product Gh-2507 are generally similar to those of Product Gh-2603-1.
  • the carboxyl carbon is not an ⁇ , ⁇ -unsaturated carbonyl carbon.
  • HMBC data of Product Gh-2507 show that: ⁇ 6.06 (H-27) is correlated with ⁇ 177.27 (C-30), ⁇ 15.92 (C-29), ⁇ 42.00 (C-28) and ⁇ 84.66 (C-13); ⁇ 5.15 (H-26) is correlated with ⁇ 42.00 (C-28), ⁇ 134.65 (C-27), ⁇ 84.66 (C-13) and ⁇ 203.53 (C-12); ⁇ 2.90 (H-28) is correlated with ⁇ 177.27 (C-30), ⁇ 15.92 (C-29), ⁇ 134.65 (C-27) and ⁇ 122.91 (C-26); and ⁇ 0.92 (H-29) is correlated with ⁇ 177.27 (C-30), ⁇ 42.00 (C-28) and ⁇ 134.65 (C-27), evidencing that the side chain attached to C-13 is (E)-2-methyl-3-butenoic acid.
  • the NOESY data of Product Gh-2507 show that: ⁇ 7.48 (H-10) is correlated with ⁇ 3.44 (H-11); ⁇ 3.44 (H-11) is correlated with ⁇ 2.30 (H 1 -21) and ⁇ 1.44 (H 2 -21); ⁇ 1.44 (H 2 -21) is correlated with ⁇ 2.56 (H-22); and ⁇ 2.56 (H-22) is correlated with ⁇ 1.72 (H-25), evidencing that the stereostructure of Product Gh-2507 in this part is identical to that of gambogic acid, gambogellic acid and epigambogellic acid, i.e., in a 11S,13R,14S,22S configuration.
  • H-29 is correlated with 2.90 (H-28), ⁇ 6.06 (H-27), ⁇ 5.15 (H-26), and ⁇ 4.20 (H 2 -40).
  • the methyl proton (H-29) is correlated with the exo-methylene protons ( ⁇ 4.56 (H 1 -40) and ⁇ 4.20 (H 2 -40)] of the isopropenyl group in the monoterpene moiety.
  • C-2 is presumed to be in a S-configuration. If C-2 is in a R configuration, no cross peaks would appear.
  • the NOESY data of Product Gh-2507 also reveal that: ⁇ 3.54 (H-4) is correlated with not only ⁇ 2.16 (H-37) but also ⁇ 1.88 (H 1 -3) and ⁇ 1.74 (H 2 -3); the methylene protons (H 1 -3 and H 2 -3) both are correlated with ⁇ 1.36 (H-19); and the axial hydrogen ⁇ 2.16 (H-37) is correlated with not only ⁇ 1.87 (H-39) but also ⁇ 1.88 (H 1 -3), ⁇ 1.55 (H 2 -20) and ⁇ 1.43 (H 1 -36), evidencing that the monoterpene ring has a chair conformation with 1,3-diaxial interaction, in which both the methyl group (C-19) connected to C-2 and the isopropenyl group connected to C-37 are in an equatorial orientation. As such, the stereostructure of the p-menthene monoterpene is in a 2S,4S,37R configuration.
  • Product Gh-2507 is identified to be a new compound having the following chemical structure:
  • Product Gh-2507 is identified by the name “ ⁇ -epigambogellic acid” ⁇ IUPAC nomenclature: [3-butenoic acid, 2-methyl-4-[(1R,3aS,5S,9S,10R,13S,16aS)-3a,4,5,7,10,11,12,13-octahydro-8-hydroxy-3,3,13-trimethyl-15-(3-methyl-2-butenyl)-10-(1-methylethenyl)-7,18-dioxo-1,5:9,13-dimethano-1H,3H,9H-furo[3.4-g]oxocino[3.2-b]xanthen-1-yl]-,(3E)-] ⁇ .
  • EIMS m/z (relative intensity): 544 [M] + (100), 529 (67), 516 (16), 501 (56), 473 (13), 435 (11), 405 (59), 389 (25), 363 (43), 349 (37), 337 (12), 307 (34), 287 (58), 259 (29), 229 (69), 215 (59), 189 (35), 147 (23), 135 (30), 105 (42), 91 (27), 83 (29), 69 (36), 55 (34).
  • Product Gh-2501 was identified to be a known compound having the following chemical structure, i.e., isomorellin:
  • EIMS m/z (relative intensity): 630 [M] + (100), 602 (19), 545 (14), 507 (36), 479 (22), 475 (18), 433 (8), 351 (27), 309 (17), 295 (38), 253 (45), 245 (16), 231 (16), 213 (13), 177 (15), 147 (8), 69 (29).
  • Product Gh-2505 was identified to be a known compound having the following chemical structure, i.e., gambogenic acid:
  • EIMS m/z (relative intensity): 630 [M] + (100), 602 (11), 545 (11), 533 (16), 507 (46), 479 (21), 475 (15), 433 (7), 419 (8), 381 (9), 357 (13), 351 (20), 309 (14), 295 (27), 253 (34), 245 (15), 231 (16), 213 (11), 177 (15), 147 (8), 135 (8), 105 (11), 69 (44).
  • Product Gh-2642 was identified to be a known compound having the following chemical structure, i.e., isogambogenic acid:
  • Product Gh-1601-A was identified to be a known compound having the following chemical structure, i.e., 30-hydroxygambogic acid:
  • Product Gh-1602 was identified to be a known compound having the following chemical structure, i.e., 30-hydroxyepigambogic acid:
  • the EIMS data of Product Gh-2641-1 show a molecular ion peak [M] + at m/z 646, which corresponds to xanthones having a molecular formula of C 38 H 46 O 9 .
  • the 1 H-NMR data of product Gh-2641-1 show that Product Gh-2641-1 has a chelated hydroxy group ( ⁇ 12.84), four olefinic protons ( ⁇ 7.46, ⁇ 5.30, ⁇ 5.19, and ⁇ 5.04), and a secondary hydroxy group ( ⁇ 4.68).
  • the NOESY data of Product Gh-2641-1 show that: ⁇ 7.46 (H-10) is correlated with ⁇ 3.48 (H-11); ⁇ 3.48 (H-11) is correlated with ⁇ 2.32 (H 1 -21); S 2.32 (H 1 -21) is correlated with ⁇ 2.39 (H-22); ⁇ 2.39 (H-22) is correlated with ⁇ 1.28 (H-24); and ⁇ 5.30 (H-27) is correlated with ⁇ 1.51 (H-29), evidencing that the stereostructure of product Gh-2641-1 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • gambogic acid i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in
  • ⁇ 4.68 (H-4) is correlated with ⁇ 1.43 (H-19), which indicates that the methyl proton connected to C-2 is in an axial orientation (or ⁇ -orientation).
  • C-2 of Product Gh-2641-1 has a configuration identical to that of gambogic acid, i.e., in an R configuration.
  • Product Gh-2641-1 is identified to be a known compound having the following chemical structure, i.e., neogambogic acid:
  • EIMS m/z (relative intensity): 646 [M] + (54), 618 (75), 573 (12), 545 (8), 520 (13), 492 (75), 491 (100), 477 (18), 449 (38), 373 (19), 349 (11), 321 (15), 295 (27), 267 (10), 252.9 (37), 245 (18), 213 (11), 188.9 (15), 176.9 (11), 109 (24), 99 (20), 69 (83); HREIMS [M] + m/z: 646.3146; calculated for C 38 H 46 O 9 , 646.3142.
  • the EIMS data of Product Gh-1631 show a molecular ion peak [M] + at m/z 646 (54) and a base peak at m/z 491 (100), and the HREIMS data of Product Gh-1631 show [M] + at m/z 646.3146, indicating that Product Gh-1631 has a molecular formula identical to that of Product Gh-2641-1 (i.e., neogambogic acid), namely, C 38 H 46 O 9 .
  • the 1 H-NMR data of Product Gh-1631 are generally similar to those of Product Gh-2641-1.
  • the HMQC data of Product Gh-1631 reveal that: ⁇ 90.00 (—OCH—) and ⁇ 25.93 (—CH 2 —) are signals that correspond to a hydroxymethine carbon and a methylene carbon adjacent to the hydroxymethine carbon, respectively.
  • ⁇ 90.00 (—OCH—) and ⁇ 25.93 (—CH 2 —) are signals that correspond to a hydroxymethine carbon and a methylene carbon adjacent to the hydroxymethine carbon, respectively.
  • Product Gh-1631 and Product Gh-2641-1 are isomers that differ from each other at the site of the hydroxy group, and Product Gh-1631 may have the hydroxy group connected to C-3.
  • the HMBC data of Product Gh-1631 show that: ⁇ 4.75 is correlated with ⁇ 168.02 (C-18), ⁇ 105.90 (C-5), ⁇ 75.77 (C-2), ⁇ 75.70 (C-2), ⁇ 25.93 (C-4) and ⁇ 23.54 (C-19); and ⁇ 3.07 is correlated with ⁇ 90.00 (C-3), ⁇ 105.90 (C-5), ⁇ 75.77 (C-2), ⁇ 75.70 (C-2), ⁇ 157.32 (C-6), ⁇ 168.02 (C-18), ⁇ 103.96 (C-17), ⁇ 101.72 (C-7) and ⁇ 158.45 (C-16), evidencing that the hydroxyl group is connected to C-3.
  • the hydroxy group on C-3 is in an axial orientation (or ⁇ -orientation), and C-3 is in an R configuration.
  • the NOESY data of Product Gh-1631 reveal that: ⁇ 7.42 (H-10) is correlated with ⁇ 3.48 (H-11); ⁇ 3.48 (H-11) is correlated with ⁇ 2.30 (H 1 -21); ⁇ 2.53 (H-22) is correlated with ⁇ 1.42 (H 2 -21); ⁇ 2.30 (H 1 -21) is correlated with ⁇ 1.23 (H-24); and ⁇ 5.32 (H-27) is correlated with ⁇ 1.597 (H-29), evidencing that the stereostructure of product Gh-1631 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • ⁇ 4.75 (H-3) is correlated with ⁇ 3.07 (H-4), ⁇ 1.42 (H-19), ⁇ 1.47 (H 2 -20) and ⁇ 2.02 (H 2 -36), which indicates that the C-3 proton is in an equatorial orientation ( ⁇ -orientation), and the methyl group attached to C-2 is in an axial orientation ( ⁇ -orientation).
  • C-2 is in an R configuration.
  • Product Gh-1631 is identified to be a new compound having the following chemical structure:
  • Product Gh-1631 is identified by the name “formoxanthone C” ⁇ IUPAC nomenclature [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,10R,11R,14aS)-3a,4,5,7,10,11-hexahydro-8,10-dihydroxy-3,3,11-trimethyl-13-(3-methyl-2-butenyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,9H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 644 [M] + (82), 616 (98), 601 (9), 598 (8), 571 (16), 533 (17), 517 (12), 490 (100), 489 (96), 475 (19), 447 (30), 433 (13), 405 (18), 371 (33), 363 (17), 309 (10), 295 (21), 253 (25), 230 (19), 213 (15), 189 (9), 173 (10), 147 (11), 105 (17), 99 (25), 69 (42); HREIMS [M] + m/z: 644.2983; calculated for C 38 H 44 O 9 , 644.2985.
  • the EIMS data of Product Gh-1050 show a molecular ion peak [M] + at m/z 644 and a base peak at m/z 490 (100), and the HREIMS data of Product Gh-1050 show [M] + at m/z 644.2983, indicating that the fragmentation pattern of Product Gh-1050 is similar to that of Product Gh-2603-2 (namely, gambogellic acid), except for having sixteen more mass units than gambogellic acid.
  • the 1 H-NMR and 13 C-NMR data of Product Gh-1050 are generally similar to those of Product Gh-2603-2.
  • the methylene protons ( ⁇ 2.03 (H 1 -20) and ⁇ 1.60 (H 2 -20)) are correlated with ⁇ 79.48 (C-2), ⁇ 48.27 (C-37), ⁇ 23.66 (C-19) and ⁇ 71.37 (C-3); and ⁇ 1.49 (H-19) is correlated with ⁇ 79.48 (C-2), ⁇ 71.37 (C-3), ⁇ 21.98 (C-36) and an aromatic carbon ( ⁇ 163.38 (C-18)). Accordingly, it can be known that the hydroxyl group is connected to C-3; C-2 is connected to C-18 of an aromatic ring via an ether bond; and C-4 is connected to C-5 of the aromatic ring.
  • the NOESY data of Product Gh-1050 show that: ⁇ 7.47 (H-10) is correlated with ⁇ 3.49 (H-11); ⁇ 3.49 (H-11) is correlated with ⁇ 2.31 (H 1 -21); ⁇ 1.39 (H 2 -21) is correlated with ⁇ 2.55 (H-22); both ⁇ 2.31 (H 1 -21) and ⁇ 2.55 (H-22) are correlated with ⁇ 1.29 (H-24); and ⁇ 5.57 (H-27) is correlated with ⁇ 1.62 (H-29), evidencing that: the stereostructure of Product Gh-1050 in this part is identical to that of gambogic acid or gambogellic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • the NOESY data of Product Gh-1050 also reveal that in addition to being correlated with ⁇ 3.65 (H-4) and ⁇ 1.31 (H-36), ⁇ 2.29 (H-37) is correlated with ⁇ 3.86 (H-3) and ⁇ 1.60 (H 2 -20), evidencing that the monoterpene ring has a chair conformation with 1,3-diaxial interaction, in which H-37 and H-3 are in an axial orientation, and both the methyl group (C-19) and the isopropenyl group are in an equatorial orientation.
  • Product Gh-1050 is identified to be a new compound having the following chemical structure:
  • Product Gh-1050 is identified by the name “3 ⁇ -hydroxygambogellic acid” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,9R,10S,13R,16aS,17S)-3a,4,5,7,10,11,12,13-octahydro-8,17-dihydroxy-3,3,13-trimethyl-15-(3-methyl-2-butenyl)-10-(1-methylethenyl)-7,18-dioxo-1,5:9,13-dimethano-1H,3H,9H-furo[3.4-g]oxocino[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 644 [M] + (10), 626 (10), 616 (12), 545 (67), 517 (19), 471 (15), 459 (6), 419 (10), 389 (21), 349 (11), 347 (20), 309 (9), 295 (17), 271 (13), 253 (20), 245 (26), 227 (21), 215 (56), 189 (23), 171 (11), 147 (16), 129 (28), 105 (35), 99 (50), 84 (43), 69 (84), 55 (100); HREIMS [M] + m/z: 644.2991; calculated for C 38 H 44 O 9 , 644.2985.
  • the EIMS data of Product Gh-3291 show a molecular ion peak [M] + at m/z 644, and the HREIMS data of Product Gh-3291 show [M] + at m/z 644.2991, indicating that Product Gh-3291 has a molecular formula of C 38 H 44 O 9 , which has 16 more mass units than the molecular formula of gambogic acid.
  • the 1 H-NMR, 13 C-NMR and HMQC data of Product Gh-3291 show that Product Gh-3291 has a C-2 side chain different from that of gambogic acid, namely, a 3-hydroxy-4-methyl-4-pentenyl group in lieu of the 4-methyl-3-pentenyl group in gambogic acid.
  • the HMBC data of Product Gh-3291 show that: in addition to being correlated with ⁇ 111.34 (C-40) and ⁇ 147.09 (C-38), the hydroxymethine proton ( ⁇ 4.00) is correlated with ⁇ 17.45 (C-39), ⁇ 29.29 (C-36) and ⁇ 37.71 (C-20); in addition to being correlated with ⁇ 37.71 (C-20), the methyl proton ( ⁇ 1.39 (H-19)) is correlated with ⁇ 81.07 (C-2) and ⁇ 124.41 (C-3); and ⁇ 5.36 (H-3) is correlated with ⁇ 81.07 (C-2), ⁇ 27.73 (C-19) and ⁇ 37.71 (C-20).
  • the NOESY data of Product Gh-3291 show that: ⁇ 7.53 (H-10) is correlated with ⁇ 3.46 (H-11); ⁇ 3.46 (H-11) is correlated with ⁇ 2.30 (H 1 -21); ⁇ 1.38 (H 2 -21) is correlated with ⁇ 2.51 (H-22) and ⁇ 1.27 (H-24); and ⁇ 6.06 (H-27) is correlated with ⁇ 81.73 (H-29), evidencing that the stereostructure of Product Gh-3291 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • gambogic acid i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond
  • the NOESY data of Product Gh-3291 also reveal that: the hydroxymethine proton ( ⁇ 4.00 (H-37)) is correlated not only with ⁇ 4.89 (H 1 -40) and ⁇ 1.66 (H-39), but also with the protons of two methylene groups ( ⁇ 1.80 (H 1 -20), ⁇ 1.54 (H 2 -20), ⁇ 1.67 (H 1 -36) and ⁇ 1.61 (H 2 -36)); and ⁇ 5.36 (H-3) is correlated with ⁇ 1.39 (H-19), ⁇ 1.80 (H 1 -20), ⁇ 1.54 (H 2 -20), ⁇ 1.67 (H 1 -36), and ⁇ 1.61 (H 2 -36). Besides, since ⁇ 1.39 (H-19) is correlated with ⁇ 1.73 (H-29), C-2 is in an R configuration.
  • Product Gh-3291 is identified to be a new compound having the following chemical structure:
  • Product Gh-3291 is identified by the name “formoxanthone D” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(3-methyl-2-butenyl)-11-(3-hydroxy-4-methyl-4-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • the 1 H-NMR, 13 C-NMR and HMQC data of Product Gh-3352 show that Product Gh-3352 has a C-17 side chain different from that of gambogic acid, namely, a 2,3-epoxy-3-methylbutyl group in lieu of the 3-methyl-2-butenyl group in gambogic acid. As compared to gambogic acid, the unsaturation number of Product Gh-3352 remains unchanged.
  • Product Gh-3352 has two tertiary methyl groups ( ⁇ 1.29 (3H, s, H-34) and ⁇ 1.27 (3H, s, H-35)) attached to an oxygen-bearing quaternary carbon. It can be known from the signals of the oxygen-bearing quaternary carbon ( ⁇ 73.24 (C-33)), the oxymethine carbon ( ⁇ 77.20 (CH)) and the methylene carbon ( ⁇ 25.89 (CH 2 ) C-31) that an epoxy group is located at C-32 and C-33.
  • HMBC data of Product Gh-3352 show that ⁇ 2.85 (H 1 -31) is correlated with ⁇ 77.20 (C-32) and ⁇ 104.83 (C-17), evidencing that the side attached to C-17 is a 2,3-epoxy-3-methylbutyl group.
  • the NOESY data of Product Gh-3352 show that: ⁇ 7.52 (H-10) is correlated with ⁇ 3.50 (H-11); ⁇ 3.50 (H-11) is correlated with ⁇ 2.33 (H 1 -21) and ⁇ 1.33 (H 2 -21); ⁇ 1.33 (H 2 -21) and ⁇ 2.49 (H-22) are correlated; ⁇ 2.49 (H-22) is correlated with ⁇ 1.74 (H-25); and ⁇ 5.58 (H-27) is correlated with ⁇ 1.69 (H-29), evidencing that the stereostructure of Product Gh-3352 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration. In addition, since ⁇ 1.69 (H-29) is correlated with ⁇ 1.45 (H-19), C-2 is in an R configuration.
  • Product Gh-3352 is identified to be a new compound having the following chemical structure:
  • Product Gh-3352 is identified by the name “formoxanthone E” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(2,3-epoxy-3-methylbutyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • the EIMS data of Product Gh-3351 show a base peak at m/z 589 (100), and the HRFABMS data of Product Gh-3351 show a pseudomolecular ion peak [M+H] + at m/z 645.3070, indicating that Product Gh-3351 has a molecular formula of C 38 H 44 O 9 , which has sixteen more mass units than the molecular formula of gambogic acid.
  • the 1 H-NMR, 13 C-NMR and HMQC data of Product Gh-3351 show that Product Gh-3351 has a C-17 side chain different from that of gambogic acid, namely a 2,3-epoxy-3-methylbutyl group in lieu of the 3-methyl-2-butenyl group in gambogic acid. As compared to gambogic acid, the unsaturation number of Product Gh-3351 remains unchanged.
  • Product Gh-3351 has two oxygen-bearing tertiary methyl protons ( ⁇ 1.28 (3H, s, H-34) and ⁇ 1.26 (3H, s, H-35)].
  • HMBC data of Product Gh-3351 show that: ⁇ 2.82 (H 1 -31) is correlated with ⁇ 77.15 (C-32), ⁇ 102.88 (C-5), ⁇ 104.81 (C-17), ⁇ 158.25 (C-16) and ⁇ 161.37 (C-18), evidencing that the side chain attached to C-17 is a 2,3-epoxy-3-methylbutyl group.
  • the NOESY data of Product Gh-3351 show that: ⁇ 7.51 (H-10) is correlated with ⁇ 3.50 (H-11); ⁇ 3.50 (H-11) is correlated with ⁇ 2.32 (H 1 -21) and ⁇ 1.30 (H 2 -21); ⁇ 1.30 (H 2 -21) is correlated with ⁇ 2.48 (H-22); ⁇ 2.48 (H-22) is correlated with ⁇ 1.73 (H-25); and ⁇ 5.56 (H-27) is correlated with ⁇ 1.68 (H-29), evidencing that the stereostructure of Product Gh-3351 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration. In addition, since ⁇ 1.68 (H-29) is correlated with ⁇ 2.03 (H-36), C-2 is in an S configuration.
  • product Gh-3351 is identified to be a new compound having the following chemical structure:
  • Product Gh-3351 is identified by the name “epiformoxanthone E” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11S,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(2,3-epoxy-3-methylbutyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 662 [M] + (6), 634 (8), 579 (100), 551 (16), 545 (9), 507 (14), 489 (6), 417 (12), 389 (4), 349 (4), 295 (5), 245 (8), 214.9 (14), 189 (8), 147 (4), 99 (7), 69 (29); HREIMS [M] + m/z: 662.3096; calculated for C 38 H 46 O 10 , 662.3091.
  • the EIMS data of Product Gh-1052 show a molecular ion peak [M] + at m/z 662 and a base peak at m/z 579 (100), and the HREIMS data of Product Gh-1052 show [M] + at m/z 662.3096, indicating that Product Gh-1052 has a molecular formula of C 38 H 46 O 10 , which has thirty-four more mass units than the molecular formula of gambogic acid.
  • the 1 H-NMR, 13 C-NMR and HMQC data of Product Gh-1052 show that Product Gh-1052 has a C-17 side chain different from that of gambogic acid, namely, a 2,3-dihydroxy-3-methylbutyl group in lieu of the 3-methyl-2-butenyl group in gambogic acid.
  • the HMQC data of Product Gh-1052 show that: C-31 ( ⁇ 25.68) is a methylene group; the secondary hydroxy group is connected to C-32 ( ⁇ 77.11); a tertiary hydroxy group is connected to C-33 ( ⁇ 73.09); and C-35 ( ⁇ 25.87) and C-34 ( ⁇ 23.65) are tertiary methyl groups.
  • the HMBC data of Product Gh-1052 show that: ⁇ 3.74 (H-32) is correlated with ⁇ 73.09 (C-33) and ⁇ 23.65 (C-34); both ⁇ 2.84 (H 1 -31) and ⁇ 2.72 (H 2 -31) are correlated with ⁇ 104.92 (C-17), ⁇ 161.47 (C-18), ⁇ 158.22 (C-16) and ⁇ 77.11 (C-32); H 1 -31 is also correlated with ⁇ 73.09 (C-33); ⁇ 1.24 (H-34) and ⁇ 1.27 (H-35) are both correlated with ⁇ 77.11 (C-32) and ⁇ 73.09 (C-33); H-34 is also correlated with ⁇ 25.87 (C-35); and H-35 is correlated with ⁇ 23.65 (C-34), evidencing that the side chain attached to C-17 is a 2,3-dihydroxy-3-methylbutyl group.
  • the NOESY data of Product Gh-1052 show that: ⁇ 7.52 (H-10) is correlated with ⁇ 3.49 (H-11); ⁇ 3.49 (H-11) is correlated with ⁇ 2.32 (H 1 -21) and ⁇ 1.33 (H 2 -21); ⁇ 1.33 (H 2 -21) is correlated with ⁇ 2.49 (H-22); ⁇ 2.49 (H-22) is correlated with ⁇ 1.73 (H-25); and ⁇ 5.63 (H-27) is correlated with ⁇ 1.69 (H-29), evidencing that the stereostructure of Product Gh-1052 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration. In addition, since ⁇ 1.37 (H-19) is correlated with ⁇ 1.69 (H-29), C-2 is in an R configuration.
  • Product Gh-1052 is identified to be a new compound having the following chemical structure:
  • Product Gh-1052 is identified by the name “formoxanthone F” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(2,3-dihydroxy-3-methylbutyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 662 [M] + (13), 634 (7), 579 (100), 551 (13), 545 (10), 507 (12), 489 (5), 417 (9), 375 (3), 349 (3), 295 (4), 245 (8), 215 (8), 213 (7), 147 (4), 105 (5), 69 (19); HREIMS [M] + m/z 662.3098; calculated for C 38 H 46 O 10 , 662.3091.
  • the EIMS data of Product Gh-1036 show a molecular ion peak [M] + at m/z 662 and a base peak at m/z 579 (100), and the HREIMS data of Product Gh-1036 show [M] + at m/z 662.3098, indicating that Product Gh-1036 has a molecular formula of C 38 H 46 O 10 , which has thirty-four more mass units than the molecular formula of gambogic acid.
  • the 1 H-NMR, 13 C-NMR and HMQC data of Product Gh-1036 show that Product Gh-1036 has a C-17 side chain different from that of gambogic acid, namely, a 2,3-dihydroxy-3-methylbutyl group in lieu of the 3-methyl-2-butenyl group in gambogic acid.
  • the HMQC data of product Gh-1036 show that: C-31 ( ⁇ 24.62) is a methylene group; a secondary hydroxy group is connected to C-32 ( ⁇ 76.57); a tertiary hydroxy group is connected to C-33 ( ⁇ 73.06); and C-34 ( ⁇ 23.56) and C-35 ( ⁇ 26.29) are tertiary methyl groups.
  • the HMBC data of Product Gh-1036 show that: in addition to being correlated with ⁇ 24.62 (C-31), ⁇ 73.06 (C-33) and ⁇ 23.56 (C-34), ⁇ 3.74 (H-32) is correlated with ⁇ 104.54 (C-17); and both ⁇ 2.87 (H 1 -31) and ⁇ 2.72 (H 2 -31) are correlated with ⁇ 76.57 (C-32), ⁇ 73.06 (C-33), ⁇ 104.54 (C-17), ⁇ 161.45 (C-18) and ⁇ 158.28 (C-16), evidencing that the side chain attached to C-17 is a 2,3-dihydroxy-3-methylbutyl group.
  • the NOESY data of Product Gh-1036 show that: ⁇ 7.52 (H-10) is correlated with ⁇ 3.49 (H-11); ⁇ 3.49 (H-11) is correlated with ⁇ 2.32 (H 1 -21) and ⁇ 1.33 (H 2 -21); ⁇ 1.33 (H 2 -21) is correlated with ⁇ 2.48 (H-22); ⁇ 2.48 (H-22) is correlated with ⁇ 1.702 (H-25); and ⁇ 5.53 (H-27) is correlated with ⁇ 1.653 (H-29), evidencing that the stereostructure of Product Gh-1036 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • ⁇ 1.653 (H-29) is correlated with ⁇ 1.78 (H 1 -20) and ⁇ 2.10 (H
  • Product Gh-1036 is identified to be a new compound having the following chemical structure:
  • Product Gh-1036 is identified by the name “epiformoxanthone F” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11S,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(2,3-dihydroxy-3-methylbutyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)] ⁇ .
  • EIMS m/z (relative intensity): 590 (32), 589 (100), 577 (24), 561 (19), 503 (44), 467 (6), 423 (8), 381 (5), 339 (4), 315 (8), 311 (3), 285 (2), 247 (4), 231 (6), 205 (2), 135 (4), 81 (3), 69 (14); HRFABMS [M+H] + m/z: 661.3019; calculated for C 38 H 45 O 10 , 661.3013.
  • the EIMS data of Product Gh-3353 show a base peak at m/z 589 (100), and the HRFABMS data of product Gh-3353 show a pseudomolecular ion peak [M+H] + at m/z 661.3019, indicating that Product Gh-3353 has a molecular formula of C 38 H 44 O 10 , which has thirty-two more mass units than the molecular formula of gambogic acid.
  • the HMBC data of Product Gh-3353 show that: ⁇ 5.15 is correlated with ⁇ 161.08 (C-18), ⁇ 159.90 (C-16), ⁇ 105.98 (C-17) and ⁇ 76.83 (C-32); and ⁇ 4.70 is correlated with ⁇ 83.75 (C-33), ⁇ 18.80 (C-34), 23.89 (C-35) and ⁇ 67.26 (C-31), evidencing that a hydroxy group is connected to C-31; an epoxy group is located at C-32 and C-33; and the side chain attached to C-17 is a 1-hydroxy-2,3-epoxy-3-methylbutyl group.
  • the NOESY data of Product Gh-3353 show that: ⁇ 7.56 (H-10) is correlated with ⁇ 3.55 (H-11); ⁇ 3.55 (H-11) is correlated with ⁇ 2.36 (H 1 -21) and ⁇ 1.27 (H 2 -21); both ⁇ 2.36 (H 1 -21) and ⁇ 1.27 (H 2 -21) are correlated with ⁇ 2.52 (H-22); ⁇ 2.52 (H-22) is correlated with ⁇ 1.82 (H-25) and ⁇ 1.26 (H-24); ⁇ 5.01 (H-27) is correlated with ⁇ 1.49 (H-29); and ⁇ 1.49 (H-29) is not correlated with ⁇ 2.05 (H-36) or ⁇ 1.76 (H 1 -20), evidencing that the stereostructure of Product Gh-3353 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30)
  • ⁇ 5.04 (H-37) is correlated with ⁇ 1.62 (H-39) and ⁇ 1.54 (H-40), and ⁇ 2.05 (H-36) is correlated with ⁇ 1.76 (H 1 -20). Since ⁇ 1.49 (H-29) is not correlated with ⁇ 2.05 (H-36) or ⁇ 1.76 (H 1 -20), C-2 has an R configuration.
  • Product Gh-3353 is identified to be a new compound having the following chemical structure:
  • Product Gh-3353 is identified by the name “formoxanthone G” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(1-hydroxy-2,3-epoxy-3-methylbutyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 590 (7), 589 (18), 577 (5), 561 (9), 503 (11), 467 (2), 423 (2), 347 (5), 315 (3), 285 (3), 247 (6), 233 (13), 231 (22), 230 (16), 215 (8), 202 (4), 131 (6), 117 (100), 115 (19), 91 (12), 69 (14); HRFABMS [M+H] + m/z: 661.3010; calculated for C 38 H 45 O 10 , 661.3013.
  • the EIMS data of Product Gh-3311 show a base peak at m/z 117 (100) but no molecular ion peak [M] + , and the HRFABMS data of Product Gh-3311 show a pseudomolecular ion peak [M+H] + at m/z 661.3010, indicating that Product Gh-3311 has a molecular formula of C 38 H 44 O 10 , which has thirty-two more mass units compared to the molecular formula of gambogic acid. As compared to gambogic acid, the unsaturation number of Product Gh-3331 remains unchanged.
  • the HMBC data of Product Gh-3311 show that: ⁇ 5.17 is correlated with ⁇ 160.99 (C-18), ⁇ 159.85 (C-16), ⁇ 106.57 (C-17) and ⁇ 76.98 (C-32); and ⁇ 4.71 is correlated with ⁇ 83.80 (C-33), ⁇ 18.91 (C-34) and ⁇ 67.16 (C-31), evidencing that the hydroxy group is connected to C-31, the epoxy group is located at C-32 and C-33, and the side chain attached to C-17 is a 1-hydroxy-2,3-epoxy-3-methylbutyl group.
  • the NOESY data of Product Gh-3311 show that: ⁇ 7.56 (H-10) is correlated with ⁇ 3.56 (H-11); ⁇ 3.56 (H-11) is correlated with ⁇ 2.37 (H 1 -21) and ⁇ 1.28 (H 2 -21); both ⁇ 2.37 (H 1 -21) and ⁇ 1.28 (H 2 -21) are correlated with ⁇ 2.54 (H-22); ⁇ 2.54 (H-22) is correlated with ⁇ 1.83 (H-25) and ⁇ 1.26 (H-24); and ⁇ 5.03 (H-27) is correlated with ⁇ 1.49 (H-29), evidencing that the stereostructure of Product Gh-3311 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration. In addition, since ⁇ 1.49 (H-29)
  • product Gh-3311 is identified to be a new compound having the following chemical structure:
  • Product Gh-3311 is identified by the name “epiformoxanthone G” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11S,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(1-hydroxy-2,3-epoxy-3-methylbutyl)-11-(4-methyl-3-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 626 [M ⁇ H 2 O] + (2), 598 (2), 545 (100), 517 (3), 499 (2), 389 (3), 347 (3), 271 (2), 245 (4), 215 (11), 189 (4), 147 (1), 105 (2), 69 (2); HRFABMS [M ⁇ H 2 O+H] + m/z: 627.2961; calculated for C 38 H 43 O 8 , 627.2958.
  • the EIMS data of Product Gh-3272 show [M ⁇ H 2 O] + (2) at m/z 626 and a base peak at m/z 545 (100), and the HRFABMS data of Product Gh-3272 show a pseudomolecular ion peak [M ⁇ H 2 O+H] + at m/z 627.2961, indicating that Product Gh-3272 has a molecular formula of C 38 H 44 O 9 , which has sixteen more mass units than the molecular formula of gambogic acid. As compared to gambogic acid, the unsaturation number of Product Gh-3272 remains unchanged.
  • Product Gh-3272 has a C-2 side chain attached different from that of gambogic acid, namely, a 4-hydroxy-4-methyl-2-pentenyl group in lieu of the 4-methyl-3-pentenyl group in gambogic acid.
  • the HMBC data of Product Gh-3272 show that: the methylene protons ( ⁇ 2.25 (H 2 -20) and ⁇ 2.36 (H 1 -20)) are correlated with ⁇ 27.39 (C-19), ⁇ 80.84 (C-2), ⁇ 120.93 (C-36) and ⁇ 142.05 (C-37), as well as an olefinic carbon ( ⁇ 123.91 (C-3)) in a pyran ring; ⁇ 5.53 (H-36) is correlated with ⁇ 44.67 (C-20), ⁇ 70.61 (C-38) and ⁇ 142.05 (C-37); and ⁇ 5.59 (H-37) is correlated with ⁇ 44.67 (C-20), ⁇ 70.61 (C-38), ⁇ 120.93 (C-36), ⁇ 29.44 (C-39) and ⁇ 29.43 (C-40), evidencing that the side chain attached to C-2 is a 4-hydroxy-4-methyl-2-pentenyl group.
  • the NOESY data of Product Gh-3272 show that: ⁇ 7.52 (H-10) is correlated with ⁇ 3.46 (H-11); ⁇ 3.46 (H-11) is correlated with ⁇ 2.29 (H 1 -21) and ⁇ 1.37 (H 2 -21); ⁇ 1.37 (H 2 -21) is correlated with ⁇ 2.49 (H-22); ⁇ 2.49 (H-22) is correlated with a gem-dimethyl group ( ⁇ 1.67 (H-25) and 1.27 (H-24)); and ⁇ 6.03 (H-27) is correlated with ⁇ 1.70 (H-29), evidencing that the stereostructure of Product Gh-3272 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • gambogic acid i.e., in a 11S
  • the olefinic proton ( ⁇ 5.53 (H-36)) is correlated not only with ⁇ 5.59 (H-37) and the methylene protons ( ⁇ 2.36 (H 1 -20) and ⁇ 2.25 (H 2 -20)), but also with the gem-dimethyl group ( ⁇ 1.16 (H-39 and H-40)), and another olefinic proton ( ⁇ 5.34 (H-3)) is correlated with ⁇ 1.38 (H-19) and ⁇ 2.25 (H 2 -20). Since ⁇ 1.38 (H-19) is correlated with ⁇ 1.70 (H-29), C-2 is in an R configuration.
  • Product Gh-3272 is identified to be a new compound having the following chemical structure:
  • Product Gh-3272 is identified by the name “formoxanthone H” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(3-methyl-2-butenyl)-11-(4-hydroxy-4-methyl-2E-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 626 [M ⁇ H 2 O] + (5), 575 (2), 545 (100), 499 (2), 471 (1), 389 (4), 347 (4), 271 (3), 245 (5), 215 (15), 189 (5), 147 (2), 105 (3), 69 (2); HRFABMS [M ⁇ H 2 O+H] + m/z: 627.2966; calculated for C 38 H 43 O 8 , 627.2958.
  • the EIMS data of Product Gh-3332 show [M ⁇ H 2 O] + (5) at m/z 626 and a base peak at m/z 545 (100), and the HRFABMS data of Product Gh-3332 show a pseudomolecular ion peak [M ⁇ H 2 O+H] + at m/z 627.2966, indicating that Product Gh-3332 has a molecular formula identical to that of product Gh-3272, C 38 H 44 O 9 , which has 16 more mass units than the molecular formula of gambogic acid or isogambogic acid. As compared to gambogic acid, the unsaturation number of Product Gh-3332 remains unchanged.
  • the EIMS, 1 H-NMR and 13 C-NMR data of Product Gh-3332 are generally similar to those of Product Gh-3272, implying that Product Gh-3332 might be an isomer of Product Gh-3272.
  • ⁇ 27,28 in product Gh-3332 is in an E configuration.
  • Product Gh-3332 is identified to be a new compound having the following chemical structure:
  • Product Gh-3332 is identified by the name “isoformoxanthone I” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(3-methyl-2-butenyl)-11-(4-hydroxy-4-methyl-2Z-pentenyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2E)-] ⁇ .
  • EIMS m/z (relative intensity): 662 [M] + (15), 647 (5), 603 (2), 545 (100), 517 (12), 499 (2), 389 (4), 347 (3), 295 (1), 245 (3), 215 (6), 189 (2), 147 (1), 105 (2), 69 (3), 59 (3); HREIMS [M] + m/z: 662.3098; calculated for C 38 H 46 O 10 , 662.3091.
  • the EIMS data of Product Gh-3261 show a molecular ion peak [M] + at m/z 662 and a base peak at m/z 545 (100), and the HREIMS data of Product Gh-3261 show [M] + at m/z 662.3098, indicating that Product Gh-3261 has a molecular formula of C 38 H 46 O 10 , which has thirty-four more mass units than the molecular formula of gambogic acid.
  • the 1 H-NMR, 13 C-NMR and HMQC data of Product Gh-3261 show that Product Gh-3261 has a C-2 side chain different from that of gambogic acid, namely, a 3,4-dihydroxy-4-methylpentyl group in lieu of the 4-methyl-3-pentenyl group in gambogic acid.
  • a secondary hydroxy group is attached to C-37 ( ⁇ 78.23); a tertiary hydroxy group is attached to C-38 ( ⁇ 73.70); and C-39 ( ⁇ 26.70) and C-40 ( ⁇ 24.28) are tertiary methyl groups.
  • the HMBC data of Product Gh-3261 show that: the hydroxymethine proton ( ⁇ 3.36 (H-37)] is correlated with ⁇ 38.73 (C-20); both ⁇ 2.04 (H 1 -20) and ⁇ 1.68 (H 2 -20) are correlated with ⁇ 25.28 (C-36), ⁇ 81.24 (C-2) and ⁇ 124.18 (C-3); ⁇ 5.36 (H-3) is correlated with ⁇ 102.49 (C-5), ⁇ 81.24 (C-2) and ⁇ 27.88 (C-19); ⁇ 1.456 (H-19) is correlated with ⁇ 81.24 (C-2), ⁇ 124.18 (C-3), ⁇ 116.18 (C-4) and ⁇ 38.73 (C-20); ⁇ 1.21 (H-39) is correlated with ⁇ 78.23 (C-37), ⁇ 73.70 (C-38) and ⁇ 24.28 (C-40); and ⁇ 1.11 (H-40) is
  • the NOESY data of Product Gh-3261 show that: ⁇ 7.49. (H-10) is correlated with ⁇ 3.50 (H-11); ⁇ 3.50 (H-11) is correlated with ⁇ 2.33 (H 1 -21) and ⁇ 1.39 (H 2 -21); ⁇ 1.39 (H 2 -21) is correlated with ⁇ 2.51 (H-22) and ⁇ 1.27 (H-24); ⁇ 2.51 (H-22) is correlated with ⁇ 1.65 (H-25); and ⁇ 5.54 (H-27) is correlated with ⁇ 1.60 (H-29), evidencing that the stereostructure of Product Gh-3261 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • gambogic acid i.e., in a 11S,13R,14S
  • Product Gh-3261 is identified to be a new compound having the following chemical structure:
  • Product Gh-3261 is identified by the name “formoxanthone J” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11R,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(3-methyl-2-butenyl)-11-(3,4-dihydroxy-4-methylpentyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • EIMS m/z (relative intensity): 662 [M] + (14), 644 (5), 603 (4), 545 (100), 517 (15), 499 (3), 419 (4), 389 (6), 347 (5), 283 (5), 245 (6), 215 (11), 213 (5), 189 (5), 147 (4), 129 (4), 117 (5), 105 (8), 91 (7), 85.9 (12), 83.9 (19), 69 (11), 59 (8), 57 (11), 55 (11); HREIMS [M] + m/z: 662.3097; calculated for C 38 H 46 O 10 , 662.3091.
  • the EIMS data of Product Gh-3271 show a molecular ion peak [M] + at m/z 662 and a base peak at m/z 545 (100), and the HREIMS data of product Gh-3271 show [M] + at m/z 662.3097, indicating that Product Gh-3271 has a molecular formula of C 38 H 46 O 10 , which has thirty-four more mass units than the molecular formula of gambogic acid.
  • the 1 H-NMR, 13 C-NMR and HMQC data of Product Gh-3271 show that Product Gh-3271 has a C-2 side chain different from that of gambogic acid, namely, a 3,4-dihydroxy-4-methylpentyl group in lieu of the 4-methyl-3-pentenyl in gambogic acid.
  • the HMQC data of Product Gh-3271 show that: ⁇ 36.88 (C-20), ⁇ 25.56 (C-36), and ⁇ 73.63 (C-38), evidencing that the secondary hydroxy group is attached to C-37, and a tertiary hydroxy group is attached to C-38.
  • HMBC data of Product Gh-3271 show that: ⁇ 3.38 (H-37) is correlated with ⁇ 36.88 (C-20); both ⁇ 2.05 (H 1 -20) and ⁇ 1.62 (H 2 -20) are correlated with ⁇ 25.56 (C-36), ⁇ 78.09 (C-37), ⁇ 80.56 (C-2), ⁇ 125.28 (C-3) and ⁇ 26.39 (C-19); ⁇ 5.46 (H-3) is correlated with ⁇ 80.56 (C-2), ⁇ 26.39 (C-19) and ⁇ 102.95 (C-5); ⁇ 1.44 (H-19) is correlated with ⁇ 80.56 (C-2), ⁇ 125.28 (C-3), ⁇ 116.13 (C-4) and ⁇ 160.44 (C-18); and ⁇ 1.18 (H-39 and H-40) is correlated with ⁇ 78.09 (C-37) and ⁇ 73.63 (C-38), evidencing that the side chain attached
  • the NOESY data of Product Gh-3271 show that: ⁇ 7.50 (H-10) is correlated with ⁇ 3.50 (H-11); ⁇ 3.50 (H-11) is correlated with ⁇ 2.34 (H 1 -21) and ⁇ 1.37 (H 2 -21); ⁇ 1.37 (H 2 -21) is correlated with ⁇ 2.50 (H-22) and ⁇ 1.27 (H-24); ⁇ 2.50 (H-22) is correlated with ⁇ 1.63 (H-25); and ⁇ 5.39 (H-27) is correlated with ⁇ 1.58 (H-29), evidencing that the stereostructure of Product Gh-3271 in this part is identical to that of gambogic acid, i.e., in a 11S,13R,14S,22S configuration, which includes H-27 and carboxyl group (C-30) in a trans relationship, and a double bond ⁇ 27,28 in a Z configuration.
  • ⁇ 3.38 (H-37) is correlated with ⁇ 1.18 (H-39 and
  • Product Gh-3271 is identified to be a new compound having the following chemical structure:
  • Product Gh-3271 is identified by the name “epiformoxanthone J” ⁇ IUPAC nomenclature: [2-butenoic acid, 2-methyl-4-[(1R,3aS,5S,11S,14aS)-3a,4,5,7-tetrahydro-8-hydroxy-3,3,11-trimethyl-13-(3-methyl-2-butenyl)-11-(3,4-dihydroxy-4-methylpentyl)-7,15-dioxo-1,5-methano-1H,3H,11H-furo[3.4-g]pyrano[3.2-b]xanthen-1-yl]-,(2Z)-] ⁇ .
  • the thirty-five products purified from fractions 1-3 are found to include 17 new compounds and 18 known compounds, as summarized in the following Table 4.
  • Products Gh-47, Gh-631, Gh-4601, Gh-4602 and Gh-2301 are found to be known compounds, the in vitro anti-cancer activities of which had been tested in U.S. Pat. No. 7,138,428 B2, these five products are not tested in the following pharmacological experiments.
  • the semi-preparative RP-HPLC elution profile as shown therein was divided into five regions: Region A, which corresponds to a retention period ranging from 0 to 13.7 minutes; Region B, which corresponds to a retention period ranging from 13.7 to 20.4 minutes; Region C, which corresponds to a retention period ranging from 20.4 to 26.1 minutes; Region D, which corresponds to a retention period ranging from 26.1 to 34.9 minutes; and Region E, which corresponds to a retention period ranging from 34.9 to 53.8 minutes.
  • the five crude fractionated products A-E were refined as follows: a crude fractionated product as obtained above was dissolved in 10 mL of acetone and then subjected to a semi-preparative RP-HPLC analysis along the lines as described in the previous section of “General Procedures,” in which a mobile phase containing 0.05% TFA (aq.) and 95% acetonitrile was used, and a gradient elution was performed according to the elution conditions shown in Table 5.
  • each of the five partially refined fractionated products thus obtained was further refined by repeating the semi-preparative RP-HPLC analysis as described in this section until a consistent elution profile was obtained.
  • five fractioned products from the product TSB-14 were obtained, i.e., TSB-14A (125 mg), TSB-14B (85 mg), TSB-14C (52 mg), TSB-14D (267 mg), and TSB-14E (1026 mg).
  • the elution profiles of the fractionated Products TSB-14A to TSB-14E contain peaks that correspond to peaks 1-12, peaks 13-15, peaks 16-20, peaks 21-24, and peaks 25-35 shown in FIG.
  • fractionated product TSB-14A contains Products Gh-3261, Gh-3271, Gh-3272, Gh-3311, Gh-3332, Gh-1036, Gh-3291, Gh-631, Gh-1052, Gh-3351, Gh-3353 and Gh-3352;
  • the fractionated product TSB-14B contains Products Gh-47, Gh-4602 and Gh-4601;
  • the fractionated product TSB-14C contains Products Gh-1601-A, Gh-1050, Gh-1602, Gh-1631 and Gh-2641-1;
  • the fractionated product TSB-14D contains Products Gh-2501, Gh-2642, Gh-2507 and Gh-2505;
  • fractionated product TSB-14E contains Products Gh-2508, Gh-2603-1, Gh-2603-2, Gh-1641, Gh-1642, Gh-2605, Gh-2606, Gh-2607-B, Gh-2607-1A, Gh-2
  • a formulation TSB-9 was obtained by mixing the product TSB-14 with brown sugar in a ratio of 9:1 (wt/wt).
  • the influence of the formulation TSB-9 upon the activity or binding ability of cancer-related proteins was analyzed by the MDS Pharma Services with reference to D. Riendeau et al. (1997), Can. J. Physiol. Pharmacol., 75:1088-1095; T. D. Warner et al. (1999), Proc. Natl. Acad. Sci. USA, 96:7563-7568; C. Ditchfiled et al. (2003), J. Cell Biol., 161:267-280; N. Gray et al. (1999), Curr. Med. Chem., 6:859-875; K.
  • cyclooxygenase-2 COX-2
  • protein serine/threonine kinases AURKB (Aurora-B kinase) and CDC2/CCNB1 (cdkl/cyclin B)
  • protein tyrosine kinases ABL1 (ABL), epidermal growth factor receptor (EGFR), ERBB2 (HER2), insulin receptor and KDR (VEGFR-2); and estrogen receptor a (ER ⁇ ).
  • ABL1 ABL
  • EGFR epidermal growth factor receptor
  • ERBB2 HER2
  • VEGFR-2 insulin receptor and KDR
  • ER ⁇ estrogen receptor a
  • Cancer-related proteins tested in pharmacological experiment 1 Cancer-related protein Biofunction Cancer type Cyclooxygenase-2 Inducing inflammation; Colorectal promoting tumor growth; cancer and inhibiting apoptosis of tumor gastric cancer cells Protein Regulating cell division, and Non-small cell lung serine/threonine resulting in abnormal cancer, brain cancer, kinase, AURKB chromosome number when and thyroid cancer (Aurora-B kinase) over-expressed; promoting carcinogenesis Protein Regulating cell division, and Nasopharyngral serine/threonine resulting in uncontrolled cell cancer kinase, division when over-expressed; CDC2/CCNB1 promoting carcinogenesis (cdk1/cyclin B) Protein Promoting cancer cell growth Chronic myelocytic tyrosine kinase, leukemia and T-cell ABL1 (ABL) acute lymphoblastic leukemia Protein Activating the signal pathway, Lung cancer and tyrosine kina
  • the acetone-extracted product TSB-14 from gamboge resin exhibits a significant inhibitory activity upon the tested cancer-related proteins.
  • these nine cancer-related proteins are known to be associated with various tumors/cancers (e.g., colorectal cancer, gastric cancer, non-small cell lung cancer, brain cancer, thyroid cancer, nasopharyngral cancer, chronic myelocytic leukemia, T-cell acute lymphoblastic leukemia, lung cancer, colon cancer, breast cancer, leukemia, liver cancer, ovarial cancer, renal cancer, pancreas cancer, and endometrial cancer), it is contemplated that the acetone-extracted product TSB-14 from gamboge resin can be used in the treatment of tumors/cancers.
  • tumors/cancers e.g., colorectal cancer, gastric cancer, non-small cell lung cancer, brain cancer, thyroid cancer, nasopharyngral cancer, chronic myelocytic leukemia, T-cell acute lympho
  • the formulation TSB-9 was milled to obtain a formulation TSB-9-W having a particle size of around 10 ⁇ m, and an in vivo analgesia test of the formulation TSB-9-W was performed by the MDS Pharma Services.
  • the mice in the TSB-9-W group were orally administered with the formulation TSB-9-W at a dose of 100 mg/Kg
  • the mice in the vehicle normal control group were orally administered with 2% Tween 80 at a dosing volume of 10 mL/Kg
  • the mice in the morphine positive control group were orally administered with morphine at a dose of 30 mg/Kg.
  • the formulation TSB-9 was milled to obtain a formulation TSB-9-W1 having a particle size of around 5 ⁇ m, and an in vivo anti-inflammation test of the formulation TSB-9-W1 was performed by the MDS Pharma Services.
  • two experimental groups i.e., TSB-9-W1-1 group and TSB-9-W1-2 group
  • control groups i.e., a vehicle normal control group and an aspirin positive control group.
  • the rats in the TSB-9-W1-1 and the TSB-9-W1-2 groups were orally administered with the formulation TSB-9-W1 at a dose of 10 mg/Kg and a dose of 30 mg/Kg, respectively, the rats in the vehicle normal control group were orally administered with 2% Tween 80 at a dosing volume of 10 mL/Kg, and the rats in the aspirin positive control group were orally administered with aspirin at a dose of 150 mg/Kg.
  • 0.1 mL of a 1% carrageenan suspension was intraplantarly injected into the right hind paws of rats in each group.
  • the volumes of the left and right hind paws of each rat were measured using a plethysmometer (#7150, UGO Basile, Italy) including a water cell (a diameter of 25 mm; #7157, UGO Basile, Italy), and the hind paw edema volume was expressed as the difference between the measured volumes of the left and right hind paws.
  • Inhibition rate (%) of hind paw edema in each group of rats was calculated using the following Equation (2):
  • the calculated inhibition rate is ⁇ 30%, it is an indication that a significant anti-inflammatory activity exists.
  • Table 9 The obtained experimental results are shown in Table 9. Referring to Table 9, as compared to the rats in the vehicle normal control group, the inhibition rates of hind paw edema calculated for the TSB-9-W1-1 group and TSB-9-W1-2 group of rats were significantly increased three hours after carrageenan injection. Specifically, the hind paw edema was inhibited by 30% in rats administered with the formation TSB-9-W1 at a dose of 30 mg/Kg. The experimental results reveal that the acetone-extracted product TSB-14 from gamboge resin has a dosage-dependent anti-inflammatory effect.
  • the in vitro anti-cancer test was primarily used to detect the effect of a candidate drug on cancer cell proliferation.
  • the working principle involved therein is the ability of viable cells to shift alamarBlue (AbD Serotec, UK) from its originally non-fluorescent oxidized state (non-fluorescent, blue) to a reduced form (fluorescent, red) having fluorescence via metabolic reaction. According to the fluorescent data result generated by the alamarBlue reagent thus obtained, the proliferation of the viable cells and cell activity can be quantified for detection.
  • a candidate drug was tested at 5 different concentrations of 0.01, 0.1, 1, 10, and 100 ⁇ g/ml, and six human cancer cell lines and a normal human cell line were used (see Table 10).
  • DMSO dimethylsulfoxide
  • mitomycin was used as a positive control.
  • IC 50 50% inhibition concentration
  • LC 50 50% lethal concentration
  • the fractionated products TSB-14A to TSB-14E according to this invention all have significant effects in inhibiting the activities or binding abilities of the nine tested cancer-related proteins.
  • these nine cancer-related proteins are known to be associated with various tumors/cancers (e.g., colorectal cancer, gastric cancer, non-small cell lung cancer, brain cancer, thyroid cancer, nasopharyngral cancer, chronic myelocytic leukemia, T-cell acute lymphoblastic leukemia, lung cancer, colon cancer, breast cancer, leukemia, liver cancer, ovarial cancer, renal cancer, pancreas cancer, and endometrial cancer), it is contemplated that the fractionated products TSB-14A to TSB-14E according to this invention can be used in the treatment of tumors/cancers.
  • tumors/cancers e.g., colorectal cancer, gastric cancer, non-small cell lung cancer, brain cancer, thyroid cancer, nasopharyngral cancer, chronic myelocytic leukemia
  • Table 16 The obtained experimental results are shown in Table 16.
  • the inhibition rates of hind paw licking calculated for the five experimental groups of mice administrated with the fractionated products TSB-14A to TSB-14E according to this invention significantly increased during the time periods of 0-20 minutes after formalin injection.
  • the inhibition rate of hind paw licking calculated for the experimental groups of mice administrated with the fractionated products TSB-14B to TSB-14E range within 62% and 100% at least during the time periods of 10-20 minutes after formalin injection, indicating that the fractionated products TSB-14A to TSB-14E according to this invention all have analgesic effects, especially with the fractionated product TSB-14E having the best one.
  • Table 17 The obtained experimental results are shown in Table 17.
  • the inhibition rates of hind paw edema calculated for the five experimental groups of rats administrated with the fractionated products TSB-14A to TSB-14E according to this invention significantly increased three hours after carrageenan injection.
  • the hind paw edema in rats administered with the fractionated products TSB-14A, TSB-14C or TSB-14E was inhibited by 30% or higher.
  • the experimental results reveal that the fractionated products TSB-14A to TSB-14E according to this invention all have an anti-inflammatory effect, especially with the fractionated product TSB-14E having the best one.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
US13/068,730 2010-06-11 2011-05-17 Fractionated products obtained from gamboge resin, and medical uses of the same Abandoned US20110305784A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US14/964,309 US20160089357A1 (en) 2010-06-11 2015-12-09 Use of fractionated products of gamboge resin in the treatment of cancer, pain, and inflammation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TW099119107A TWI432191B (zh) 2010-06-11 2010-06-11 分離自藤黃樹脂的化合物以及包含有此等化合物的藥學組成物
TW099119107 2010-06-11

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US14/964,309 Division US20160089357A1 (en) 2010-06-11 2015-12-09 Use of fractionated products of gamboge resin in the treatment of cancer, pain, and inflammation

Publications (1)

Publication Number Publication Date
US20110305784A1 true US20110305784A1 (en) 2011-12-15

Family

ID=44951548

Family Applications (4)

Application Number Title Priority Date Filing Date
US13/068,730 Abandoned US20110305784A1 (en) 2010-06-11 2011-05-17 Fractionated products obtained from gamboge resin, and medical uses of the same
US13/068,716 Active 2033-08-08 US9498463B2 (en) 2010-06-11 2011-05-17 Compound obtained from gamboge resin, and medical uses of the same
US14/964,309 Abandoned US20160089357A1 (en) 2010-06-11 2015-12-09 Use of fractionated products of gamboge resin in the treatment of cancer, pain, and inflammation
US15/227,926 Abandoned US20160338991A1 (en) 2010-06-11 2016-08-03 Novel compound obtained from gamboge resin, and medical uses of the same

Family Applications After (3)

Application Number Title Priority Date Filing Date
US13/068,716 Active 2033-08-08 US9498463B2 (en) 2010-06-11 2011-05-17 Compound obtained from gamboge resin, and medical uses of the same
US14/964,309 Abandoned US20160089357A1 (en) 2010-06-11 2015-12-09 Use of fractionated products of gamboge resin in the treatment of cancer, pain, and inflammation
US15/227,926 Abandoned US20160338991A1 (en) 2010-06-11 2016-08-03 Novel compound obtained from gamboge resin, and medical uses of the same

Country Status (4)

Country Link
US (4) US20110305784A1 (zh)
EP (6) EP2395006B1 (zh)
JP (2) JP5558408B2 (zh)
TW (1) TWI432191B (zh)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150298165A1 (en) * 2012-03-26 2015-10-22 Silcotek Corp. Coated article and chemical vapor deposition process
CN113274423A (zh) * 2020-02-19 2021-08-20 台湾森本生物科技开发股份有限公司 含有得自于藤黄树脂的丙酮提取产物的药学组合物以及由该组合物所制得的配方
US11131020B2 (en) 2015-09-01 2021-09-28 Silcotek Corp. Liquid chromatography system and component
US11618970B2 (en) 2019-06-14 2023-04-04 Silcotek Corp. Nano-wire growth
US12036765B2 (en) 2017-09-13 2024-07-16 Silcotek Corp Corrosion-resistant coated article and thermal chemical vapor deposition coating process
EP4620457A1 (en) 2024-03-18 2025-09-24 Taiwan Sunpan Biotechnology Development Co., Ltd. Sustained-release formulation containing acetone extracted product of gamboge resin
US12473635B2 (en) 2020-06-03 2025-11-18 Silcotek Corp. Dielectric article
US12522732B2 (en) 2010-10-05 2026-01-13 Silcotek Corp. Amorphous coating

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI432191B (zh) 2010-06-11 2014-04-01 Taiwan Sunpan Biotechnology Dev Co Ltd 分離自藤黃樹脂的化合物以及包含有此等化合物的藥學組成物
CN102617590A (zh) * 2012-03-07 2012-08-01 广州牌牌生物科技有限公司 一种新藤黄酸制备工艺
CN102603767A (zh) * 2012-03-07 2012-07-25 广州牌牌生物科技有限公司 一种藤黄酸分离纯化生产工艺
CN103664986B (zh) * 2013-11-28 2015-11-25 江苏康缘药业股份有限公司 从藤黄中提取的抗肿瘤化合物及其制备方法与用途
CN103664979A (zh) * 2013-11-28 2014-03-26 江苏康缘药业股份有限公司 从藤黄中提取的抗肿瘤化合物及其制备方法与用途
CN103664984A (zh) * 2013-11-28 2014-03-26 江苏康缘药业股份有限公司 从藤黄中提取的抗肿瘤化合物及其制备方法与用途
CN103664983A (zh) * 2013-11-28 2014-03-26 江苏康缘药业股份有限公司 从藤黄中提取的抗肿瘤化合物及其制备方法与用途
CN105213366B (zh) * 2014-07-03 2018-11-16 上海中医药大学 藤黄酮化合物的医药用途及其药物组合物
CN104817569B (zh) * 2015-03-07 2017-11-03 宝鸡文理学院 一种同时分离藤黄中四种藤黄酸类成分的方法
CN107648217B (zh) * 2017-09-29 2020-08-18 中国农业科学院哈尔滨兽医研究所 新藤黄酸或其衍生物在制备用于预防和/或治疗由细菌引起的相关疾病的药物中的用途
CN111166738B (zh) * 2020-01-10 2022-06-14 桂林医学院 毛蕊异黄酮衍生物在制备抑制内皮细胞增殖药物中的应用
CN113880857B (zh) * 2021-11-11 2023-03-10 山东大学 多异戊烯基取代的笼状氧杂蒽酮类化合物及其制备方法和应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050261363A1 (en) * 2004-05-21 2005-11-24 Taiwan Sunpan Biotechnology Development Co., Ltd. Compounds isolated from gamboge resin having activity in inhibiting the growth of tumor/cancer cells and pharmaceutical compositions comprising the same

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6462041B1 (en) 1999-05-21 2002-10-08 Cytovia, Inc. Gambogic acid, analogs and derivatives as activators of caspases and inducers of apoptosis
CN1245407C (zh) 2002-06-17 2006-03-15 杭州博大药物研究所 藤黄酸类化合物的复合物,其制备方法和以该复合物为活性成份的药物组合物
CN1235580C (zh) 2002-08-14 2006-01-11 南京海光应用化学研究所 总藤黄酸制剂及其制备方法
CN1289505C (zh) 2003-04-08 2006-12-13 王先荣 新化合物藤黄新酸的化学结构及以其为活性成份的药物制剂和用途
US7622497B2 (en) 2003-12-18 2009-11-24 Cytovia, Inc. Derivatives of gambogic acid and analogs as activators of caspases and inducers of apoptosis
CN100413868C (zh) 2004-05-21 2008-08-27 台湾森本生物科技开发股份有限公司 分离自藤黄树脂并具有抑制肿瘤/癌细胞生长活性的化合物以及包含其的药物组合物
US7592367B2 (en) 2005-12-23 2009-09-22 Hong Kong Jockey Club Institute Of Chinese Medicine Ltd. Compounds from Garcinia hanburyi, their use in treating cancer and method of separating epimers thereof
CN1927861B (zh) * 2006-07-06 2011-01-26 中国药科大学 一种藤黄酸衍生物及其制备方法和在制药中的应用
TWI432191B (zh) 2010-06-11 2014-04-01 Taiwan Sunpan Biotechnology Dev Co Ltd 分離自藤黃樹脂的化合物以及包含有此等化合物的藥學組成物

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050261363A1 (en) * 2004-05-21 2005-11-24 Taiwan Sunpan Biotechnology Development Co., Ltd. Compounds isolated from gamboge resin having activity in inhibiting the growth of tumor/cancer cells and pharmaceutical compositions comprising the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Wang et al, Reversal of a full-length mutant huntingtin neuronal cell phenotype by chemical inhibitors of polyglutamine-mediated aggregation, BMC neuroscience (2005), 6: 1-12. *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12522732B2 (en) 2010-10-05 2026-01-13 Silcotek Corp. Amorphous coating
US20150298165A1 (en) * 2012-03-26 2015-10-22 Silcotek Corp. Coated article and chemical vapor deposition process
US11131020B2 (en) 2015-09-01 2021-09-28 Silcotek Corp. Liquid chromatography system and component
US12037685B2 (en) 2015-09-01 2024-07-16 Silcotek Corp Liquid chromatography system and component
US12291778B2 (en) 2015-09-01 2025-05-06 Silcotek Corp. Liquid chromatography system and component
US12036765B2 (en) 2017-09-13 2024-07-16 Silcotek Corp Corrosion-resistant coated article and thermal chemical vapor deposition coating process
US11618970B2 (en) 2019-06-14 2023-04-04 Silcotek Corp. Nano-wire growth
CN113274423A (zh) * 2020-02-19 2021-08-20 台湾森本生物科技开发股份有限公司 含有得自于藤黄树脂的丙酮提取产物的药学组合物以及由该组合物所制得的配方
EP3868365A1 (en) 2020-02-19 2021-08-25 Taiwan Sunpan Biotechnology Development Co., Ltd. Pharmaceutical composition containing acetone-extracted product from gamboge resin, and formulation manufactured from such composition
US12473635B2 (en) 2020-06-03 2025-11-18 Silcotek Corp. Dielectric article
EP4620457A1 (en) 2024-03-18 2025-09-24 Taiwan Sunpan Biotechnology Development Co., Ltd. Sustained-release formulation containing acetone extracted product of gamboge resin

Also Published As

Publication number Publication date
EP2684885A1 (en) 2014-01-15
TW201143764A (en) 2011-12-16
EP2395006B1 (en) 2014-10-22
JP2011256162A (ja) 2011-12-22
EP2395007B1 (en) 2014-06-25
JP2011256161A (ja) 2011-12-22
EP2395007A1 (en) 2011-12-14
US20110306658A1 (en) 2011-12-15
US20160089357A1 (en) 2016-03-31
US20160338991A1 (en) 2016-11-24
EP2684884B1 (en) 2016-04-27
EP2395006A1 (en) 2011-12-14
EP2684884A1 (en) 2014-01-15
EP2684882A1 (en) 2014-01-15
JP5441947B2 (ja) 2014-03-12
HK1163087A1 (zh) 2012-09-07
TWI432191B (zh) 2014-04-01
EP2684883A1 (en) 2014-01-15
US9498463B2 (en) 2016-11-22
HK1163086A1 (zh) 2012-09-07
JP5558408B2 (ja) 2014-07-23

Similar Documents

Publication Publication Date Title
EP2395007B1 (en) Fractionated products obtained from gamboge resin, and medical uses of the same
Zhang et al. Cytotoxic and anti-inflammatory prenylated benzoylphloroglucinols and xanthones from the twigs of Garcinia esculenta
Qin et al. Acylphloroglucinol derivatives from the twigs and leaves of Callistemon salignus
CN102276621B (zh) 分离自藤黄树脂的化合物暨其衍生物,以及包含有此等化合物与衍生物的药学组成物
CN104892713B (zh) 葫芦素c及其类似物的制备方法与应用
Wang et al. Hyperacmosins EG, three new homoadamantane-type polyprenylated acylphloroglucinols from Hypericum acmosepalum
Li et al. Acylphloroglucinol-monoterpene meroterpenoids from Eucalyptus tereticornis and their inhibitory activity against ATP citrate lyase
WO2008109717A1 (en) Compositions and methods for treating cancer
Qin et al. Meroterpenoid dimers from Ganoderma mushrooms and their biological activities against triple negative breast cancer cells
Yang et al. Neoclerodane diterpenoids from aerial parts of Scutellaria barbata
CN100413868C (zh) 分离自藤黄树脂并具有抑制肿瘤/癌细胞生长活性的化合物以及包含其的药物组合物
Qian et al. Two new compounds from Carpesium abrotanoides
Ma et al. Novel cassane diterpenes from the seeds of Caesalpinia decapetala and their antiproliferative activity
TWI446907B (zh) 從藤黃樹脂所得到的分離部分以及含有此等分離部分的藥學組成物
CN112125804B (zh) 一种续随子二萜类化合物及其制备方法和抗白血病用途
CN103421021B (zh) 分离自藤黄树脂的化合物暨其衍生物，以及包含有此等化合物与衍生物的药学组成物
HK1163087B (zh) 得自於藤黄树脂的经分馏的产物及其医药用途
CN110483540B (zh) 含氮杂环混源萜类物质的制备及应用
HK1163086B (zh) 得自於藤黄树脂的新颖化合物及其医药用途
US20140194499A1 (en) Polyprenylated Benzoylphloroglucinols With Anticancer Activity
Guo et al. Discovery of tetrahydrothiazolopyridine-incorporated curcumol derivatives as novel and highly potent anti-cancer agents
JP2009274956A (ja) ニーム種子由来の悪性腫瘍治療薬
HK1084102B (zh) 分离自藤黄树脂并具有抑制肿瘤/癌细胞生长活性的化合物以及包含其的药物组合物

Legal Events

Date Code Title Description
AS Assignment

Owner name: TAIWAN SUNPAN BIOTECHNOLOGY DEVELOPMENT CO., LTD.,

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:LEE, SEN-BIN;REEL/FRAME:026428/0670

Effective date: 20110421

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION