DD239209A1 - PROCESS FOR THE PREPARATION OF O-ALKYL SUBSTITUTED GLYCERO AND DESOXYGLYCEROPHOSPHO SERINES - Google Patents
PROCESS FOR THE PREPARATION OF O-ALKYL SUBSTITUTED GLYCERO AND DESOXYGLYCEROPHOSPHO SERINES Download PDFInfo
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- DD239209A1 DD239209A1 DD27856185A DD27856185A DD239209A1 DD 239209 A1 DD239209 A1 DD 239209A1 DD 27856185 A DD27856185 A DD 27856185A DD 27856185 A DD27856185 A DD 27856185A DD 239209 A1 DD239209 A1 DD 239209A1
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- German Democratic Republic
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- serines
- preparation
- alkyl
- desoxyglycerophospho
- alkyl substituted
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- 238000000034 method Methods 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 150000003355 serines Chemical class 0.000 title description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000002314 glycerols Chemical class 0.000 claims abstract description 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 abstract description 12
- 229960001153 serine Drugs 0.000 abstract description 7
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 102000011420 Phospholipase D Human genes 0.000 abstract description 4
- 108090000553 Phospholipase D Proteins 0.000 abstract description 4
- 238000006243 chemical reaction Methods 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 150000002148 esters Chemical class 0.000 abstract description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- -1 alkyl radical Chemical class 0.000 description 5
- 150000008106 phosphatidylserines Chemical class 0.000 description 4
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical class OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 239000008351 acetate buffer Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical group [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 235000004400 serine Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 244000178937 Brassica oleracea var. capitata Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000003327 cancerostatic effect Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000008103 phosphatidic acids Chemical class 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Ziel der Erfindung ist es, ein Verfahren zur Herstellung von 0-alkylsubstituierten Glycero- bzw. Desoxyglycerophospho-L-serinen zu entwickeln. Erfindungsgemaess werden diese Verbindungen durch Reaktion von 0-alkylsubstituierten Glycero- bzw. Desoxyglycerophosphorsaeureestern mit L-Serin unter der Einwirkung von Phospholipase D hergestellt.The aim of the invention is to develop a process for the preparation of 0-alkyl-substituted glycero- or deoxyglycerophospho-L-serines. According to the invention, these compounds are prepared by reaction of 0-alkyl-substituted glycerol or deoxyglycerophosphoric acid esters with L-serine under the action of phospholipase D.
Description
in der R1 einen Alkylrest mit 5 bis 30 C-Atomen und R2 ein Wasserstoffatom oder eine Alkoxygruppe mit 5 bis 30 C-Atomen bedeuten, und von deren Salzen, dadurch gekennzeichnet, daß O-alkylsubstituierte Glycero- bzw. Desoxyglycerophorsäureester der allgemeinen Formel II, in der R1 und R2 die bereits bekannten Bedeutungen besitzen und X einen Methylrest oder einen Alkylrest mit 2 bis 6 C-Atomen, der auch durch OH, Cl, Br, NH2, NHCH3, N(CH3I2 oder N(CH3I3 substituiert sein kann.in which R 1 is an alkyl radical having 5 to 30 C atoms and R 2 is a hydrogen atom or an alkoxy group having 5 to 30 C atoms, and of their salts, characterized in that O-alkyl-substituted glycerol or Desoxyglycerophorsäureester the general formula II, in which R 1 and R 2 have the already known meanings and X is a methyl radical or an alkyl radical having 2 to 6 C atoms, which is also represented by OH, Cl, Br, NH 2 , NHCH 3 , N (CH 3 I 2 or N (CH 3 I 3 may be substituted.
CH0-O-R1 2 CH 0 -OR 1 2
IIII
iiii
CH2-O-P-O-X 0"CH 2 -OPOX 0 "
bedeutet, mit L-Serin in Anwesenheit von Phospholipase D umgesetzt und das entstandene Phosphoserin-Derivat nach an sich üblichen Methoden isoliert und gereinigt wird.means reacted with L-serine in the presence of phospholipase D and the resulting phosphoserine derivative is isolated and purified by conventional methods.
Verfahren zur Herstellung von O-alkylsubstituierten Glycero- bzw. Desoxyglycerophospho-L-serinen der allgemeinen Formel I,Process for the preparation of O-alkyl-substituted glycero- or deoxyglycerophospho-L-serines of the general formula I,
CH9-O-R1 1 2 CH-R2 0 CH 9 -OR 1 1 2 CH-R 2 0
I iiI ii
CH0-O-P-O-CH0-CH-COOHCH 0 -OPO-CH 0 -CH-COOH
OH NH2 OH NH 2
in der R1 einen Alkylrest mit 5 bis 30 C-Atomen und R2 ein Wasserstoffatom oder eine Alkoxygruppe mit 5 bis 30 C-Atomen bedeuten, und von deren Salzen.in which R 1 is an alkyl radical having 5 to 30 C atoms and R 2 is a hydrogen atom or an alkoxy group having 5 to 30 C atoms, and of their salts.
Diese Verbindungen sind Alkylanaloga natürlich vorkommender Phosphatidylserine bzw. Lysophosphatidylserine. Infolge des Vorliegens einer Ethergruppierung anstelle einer Estergruppierung sind diese Substanzen durch die Phospholipasen ΑΊ und A2 nicht spaltbar. Wegen dieser erhöhten Biostabilität sind diese Verbindungen interessante Untersuchungsobjekte, zum Beispiel für eine Reihe von biologischen Prozessen, an denen natürliche Phosphatidylserine beteiligt sind. Anwendungsgebiet der Erfindung ist die pharmazeutische bzw. chemische Industrie.These compounds are alkyl analogs of naturally occurring phosphatidylserines and lysophosphatidylserines, respectively. Due to the presence of an ether moiety instead of an ester group, these substances are not cleavable by the phospholipases Α Ί and A 2 . Because of this increased biostability, these compounds are interesting objects of study, for example, for a number of biological processes involving natural phosphatidylserines. Field of application of the invention is the pharmaceutical or chemical industry.
Bekanntlich lassen sich Phosphatidylserine durch Reaktion von Phosphatidsäuren oder deren Derivaten mit Serinen, deren Amino- und Carboxylgruppe im allgemeinen geschützt ist, oder durch Umsetzung von O-Acylglycerohalohydrinen mit geschützten Phosphoserinen erhalten (H.Eibl, Chem. Phys. Lipids, 26 [1980] 40&-429; A.J.SIotb'oom et al., Chem. Phys.It is known that phosphatidylserines can be obtained by reaction of phosphatidic acids or their derivatives with serines whose amino and carboxyl groups are generally protected, or by reacting O-acylglycerohalohydrins with protected phosphoserines (H.Eibl, Chem. Phys. Lipids, 26 [1980] 40 &42; AJSIotb'oom et al., Chem. Phys.
Lipids, 5 [1970] 301-397; A. Hermetter et al., Chem. Phys. Lipids, 30 [1982] 35-45).Lipids, 5 [1970] 301-397; Hermetter et al., Chem. Phys. Lipids, 30 [1982] 35-45).
Eine weitere Möglichkeit zur Synthese von Phosphatidylserinen besteht in der enzymatisch katalysierten Übertragung des Phosphatidylrestes, zum Beispiel aus Phosphatidylcholins, auf L-Serin (P. Comfurius et al., Biochim. Biophys. Acta, 488 [1977]Another possibility for the synthesis of phosphatidylserines is the enzymatically catalyzed transfer of the phosphatidyl radical, for example phosphatidylcholine, to L-serine (P. Comfurius et al., Biochim. Biophys. Acta, 488 [1977]
Verfahren zur Synthese der O-alkylsubstituierten Glycero- sowie Desoxyglycerophospho-L-serine der allgemeinen Formel I sind bisher in der Literatur nicht beschrieben worden.Processes for the synthesis of the O-alkyl-substituted glycerol and deoxyglycerophospho-L-serines of the general formula I have hitherto not been described in the literature.
Ziel der Erfindung ist es, ein Verfahren zur Herstellung der Verbindungen der allgemeinen Formel I zu entwickeln.The aim of the invention is to develop a process for the preparation of the compounds of general formula I.
Erfindungsgemäß werden die 0-alkylsubstituierten Glycero- bzw. Desoxyglycerophospho-L-serine der allgemeinen Formel I erhalten, indem man die O-alkylsubstituierten Glycero- bzw. Desoxyglycerophosphosäureester der allgemeinen Formel II,According to the invention, the 0-alkyl-substituted glycerol or deoxyglycerophospho-L-serines of the general formula I are obtained by reacting the O-alkyl-substituted glycerol or deoxyglycerophosphoic acid esters of the general formula II
CH9-O-R1 CH 9 -OR 1
1 *" 2 CU-P, 0 1 * "2 CU-P, 0
CH0-O-P-O-X 0"CH 0 -OPOX 0 "
in der R1 und R2 die bereits bekannten Bedeutungen besitzen und X einen Methylrest oder einen Alkylrest, mit 2 bis 6 C-Atomen, der auch durch OH, Cl, Br, NH2, NHCH3, N(CH3I2 oder N(CH3)3 substituiert sein kann bedeutet, mit L-Serin in Anwesenheit von Phospholipase D zur Umsetzung bringt und das entstandene Phosphorserin-Derivat nach üblichen Methoden isoliert. Im ein-zelnen erfolgt die Umsetzung, indem man eine Lösung oder Suspension eines Phospholipids der Formel Il in einer hochkonzentrierten Lösung von L-Serin in einem wäßrigen Puffersystem, zum Beispiel Acetat- und Tris-Puffer. Bei pH-Werten zwischen 4,8 und 8,5 in Gegenwart einer 0,01 bis 0,1 M Lösung eines Calciumsalzes, zum Beispiel Calciumchlorid, unter der Einwirkung von Phcspholipase D bei Temperaturen zwischen 10 und 50°C reagieren läßt, wobei dem Reaktionsgemisch Diethylether oder ein Gemisch von Diethylether mit weiteren organischen Lösungsmitteln, zum Beispiel Chloroform, zugesetzt wird. Im allgemeinen erfolgt die Umsetzung in einem Zeitraum von 0,5 bis 24 Stunden. Der Reaktionsablauf läßt sich durch Dünnschichtchromatographie kontrollieren. Um Ausbeuteverluste infolge Hydrolyse während der Aufarbeitung zu vermeiden, wird zur Desaktivierung des Enzyms eine 0,1 M EDTA-Lösung zum Reaktionsgemisch gegeben und darauf das entstandene Phosphoserin-Derivat auf übliche Weise isoliert. Das erfindungsgemäße Verfahren ermöglicht die Synthese der Racemate und der optischen Stereoisomeren vom Typ I (bei R2 Φ H).in which R 1 and R 2 have the already known meanings and X is a methyl radical or an alkyl radical having 2 to 6 C atoms, which is also represented by OH, Cl, Br, NH 2 , NHCH 3 , N (CH 3 I 2 or N (CH 3 ) 3 may be substituted with L-serine in the presence of phospholipase D and the isolated Phosphorserin derivative isolated by conventional methods.In the individual implementation by reacting a solution or suspension of a phospholipid of formula II in a highly concentrated solution of L-serine in an aqueous buffer system, for example acetate and Tris buffer, at pHs between 4.8 and 8.5 in the presence of a 0.01 to 0.1 M solution of a Calcium salt, for example calcium chloride, under the action of Phcspholipase D react at temperatures between 10 and 50 ° C, wherein the reaction mixture diethyl ether or a mixture of diethyl ether with other organic solvents, for example chloroform, is added The implementation takes place within a period of 0.5 to 24 hours. The course of the reaction can be monitored by thin-layer chromatography. In order to avoid losses of yield due to hydrolysis during the work-up, a 0.1 M EDTA solution is added to the reaction mixture to deactivate the enzyme, and the resulting phosphoserine derivative is then isolated in the usual way. The process according to the invention enables the synthesis of the racemates and the optical stereoisomers of type I (in the case of R 2 Φ H).
Die erfindungsgemäß hergestellten Verbindungen besitzen physiologische Aktivität. Sie sind cancerostatisch wirksam und hemmen zum Beispiel das Wachstum von Ehrlich Ascites-Zellen in vitro bereits bei sehr geringen Konzentrationen. Die Erfindung wird an nachstehendem Beispiel erläutert:The compounds according to the invention have physiological activity. They are cancerostatic and inhibit, for example, the growth of Ehrlich ascites cells in vitro even at very low concentrations. The invention is illustrated by the following example:
2-Desoxy-1-0-hexadecylglycero-3-phospho-L-serin2-deoxy-1-0-hexadecylglycero-3-phospho-L-serine
Formel I: R1 = C16H33, R2 = H)Formula I: R 1 = C 16 H 33 , R 2 = H)
Eine Mischung von 1 g L-Serin, 1,9ml 1,0M Acetatpuffer (pH 5,6) mit 0,1 M CaCI2,40 mg 2-Desoxy-i-O-hexadecylglycerophosphorsäureethylester (II: R1= Ci6H33, R2 = H, X = C2H5), 2ml Ether/Chloroform 9:1, v/v) und 100mg eines aus etwa 500g Weißkohl gewonnenen Phospholipase-D-Präparates wird 4 Stunden bei 40CC intensiv gerührt. Nach dem Abkühlen auf Raumtemperatur werden 4,35 ml 0,1 M EDTA-Lösung hinzugegeben. Die organischen Lösungsmittel werden durch Einleiten von Stickstoff entfernt. Die Mischung wird mit dem 4,3fachen Volumen Chloroform/Methanol (5:8, v/v) 30 Minuten gerührt und das sich hierbei ausscheidende unumgesetzte Serin durch Absaugen entfernt.A mixture of 1 g L-serine, 1.9 ml 1.0M acetate buffer (pH 5.6) with 0.1 M CaCl 2 , 40 mg 2-deoxy-iO-hexadecylglycerophosphorsäureethylester (II: R 1 = Ci 6 H 33 , R 2 = H, X = C 2 H 5 ), 2 ml of ether / chloroform 9: 1, v / v) and 100 mg of a phospholipase D preparation obtained from about 500 g of white cabbage is stirred intensively at 40 ° C. for 4 hours. After cooling to room temperature, 4.35 ml of 0.1 M EDTA solution are added. The organic solvents are removed by introducing nitrogen. The mixture is stirred with 4.3 times the volume of chloroform / methanol (5: 8, v / v) for 30 minutes and the resulting unreacted serine is removed by suction.
Das Filtratwird mit 1 Volumen Wasser und 3,7 Volumen Chloroform 10 Minuten gerührt, die organische Phase abgetrennt und eingeengt. Der erhaltene Rückstand wird an 20g Carboxymethylcellulose (Servacel CM 52) säulenchromatographisch getrennt, wobei die Elution nacheinander mit 75 ml Chloroform (Fraktion 1), je 500 ml Chloroform/Methanol (9:1,8:2,7:3,1:1, v/v, Fraktionen 2 bis 5) vorgenommen wird. Das Phosphoserin-Derivat wird aus Fraktion 5 in reiner Form erhalten (15 mg). DC (Merck Kieselgel 60, Fertigplatte):The filtrate is stirred with 1 volume of water and 3.7 volumes of chloroform for 10 minutes, the organic phase separated and concentrated. The residue obtained is separated by column chromatography on 20 g of carboxymethylcellulose (Servacel CM 52), eluting successively with 75 ml of chloroform (fraction 1), 500 ml each of chloroform / methanol (9: 1.8: 2.7: 3.1: 1 , v / v, fractions 2 to 5). The phosphoserine derivative is obtained from fraction 5 in pure form (15 mg). TLC (Merck Kieselgel 60, finished plate):
Rf 0,13CHCi3ZCH3OHZH2O, 50:25:4, v/v/v).Rf 0.13 CHCl 3 ZCH 3 OHZH 2 O, 50: 25: 4, v / v / v).
Claims (1)
Priority Applications (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD27856185A DD239209A1 (en) | 1985-07-15 | 1985-07-15 | PROCESS FOR THE PREPARATION OF O-ALKYL SUBSTITUTED GLYCERO AND DESOXYGLYCEROPHOSPHO SERINES |
| EP86904150A EP0229128B1 (en) | 1985-07-03 | 1986-07-02 | Derivatives of glycero-3(2)-phospho-l-serine and pharmaceutical preparations containing them |
| AT86904150T ATE53214T1 (en) | 1985-07-03 | 1986-07-02 | GLYCERO-3(2)-PHOSPHO-L-SERINE DERIVATIVES AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM. |
| DE8686904150T DE3671630D1 (en) | 1985-07-03 | 1986-07-02 | GLYCERO-3 (2) -PHOSPHO-L-SERINE DERIVATIVES AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM. |
| PCT/EP1986/000390 WO1987000173A1 (en) | 1985-07-03 | 1986-07-02 | Derivatives of glycero-3(2)-phospho-l-serine and pharmaceutical preparations containing them |
| JP61503925A JPH0751588B2 (en) | 1985-07-03 | 1986-07-02 | Glycero-3 (2) -phospho-L-serine derivative or salt thereof and pharmaceutical preparation containing the same |
| HU862805A HU198076B (en) | 1985-07-03 | 1986-07-03 | Process for producing o-alkylated glycerophospho- and deoxyglycerophosphorine derivatives and pharmaceutical compositions comprising these compounds as active ingredient |
| FI870732A FI82473C (en) | 1985-07-03 | 1987-02-20 | Process for the preparation of pharmacologically valuable glycero-3 (2) -phospho-L-cerine derivatives |
| NO87870834A NO169171C (en) | 1985-07-03 | 1987-02-27 | ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE GLYCERO-3 (2) -PHOSPHO-L SERIN DERIVATIVES |
| DK106287A DK167978B1 (en) | 1985-07-03 | 1987-03-02 | GLYCERO-3 (2) -PHOSPHO-L-SERINE DERIVATIVES AND SALTS THEREOF, PROCEDURE FOR PREPARING SUCH COMPOUNDS AND PHARMACEUTICAL PREPARATIONS CONTAINING THESE |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD27856185A DD239209A1 (en) | 1985-07-15 | 1985-07-15 | PROCESS FOR THE PREPARATION OF O-ALKYL SUBSTITUTED GLYCERO AND DESOXYGLYCEROPHOSPHO SERINES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD239209A1 true DD239209A1 (en) | 1986-09-17 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD27856185A DD239209A1 (en) | 1985-07-03 | 1985-07-15 | PROCESS FOR THE PREPARATION OF O-ALKYL SUBSTITUTED GLYCERO AND DESOXYGLYCEROPHOSPHO SERINES |
Country Status (1)
| Country | Link |
|---|---|
| DD (1) | DD239209A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4916249A (en) * | 1985-07-03 | 1990-04-10 | Hans Brachwitz | Glycero-3(2)-phospho-L-serine derivatives and salts thereof |
-
1985
- 1985-07-15 DD DD27856185A patent/DD239209A1/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4916249A (en) * | 1985-07-03 | 1990-04-10 | Hans Brachwitz | Glycero-3(2)-phospho-L-serine derivatives and salts thereof |
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