TWI324607B - - Google Patents

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Publication number: TWI324607B
Authority: TW; Taiwan
Prior art keywords: sugar chain; mixture; aspartate; sugar; derivative
Prior art date: 2002-09-24

Application number

TW91121856A

Other languages

English (en)

Chinese (zh)

Inventor

Kajihara Yasuhiro

Original Assignee

Otsuka Chemical Co Ltd

Kajihara Yasuhiro

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.)

2002-09-24

Filing date

2002-09-24

Publication date

2010-05-11

2002-09-24 Application filed by Otsuka Chemical Co Ltd, Kajihara Yasuhiro filed Critical Otsuka Chemical Co Ltd

2002-09-24 Priority to TW91121856A priority Critical patent/TWI324607B/zh

2010-05-11 Application granted granted Critical

2010-05-11 Publication of TWI324607B publication Critical patent/TWI324607B/zh

Links

235000000346 sugar Nutrition 0.000 claims description 495
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical class OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 183
150000001875 compounds Chemical class 0.000 claims description 183
239000000203 mixture Substances 0.000 claims description 139
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 130
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 107
235000010357 aspartame Nutrition 0.000 claims description 65
229940009098 aspartate Drugs 0.000 claims description 65
102000004190 Enzymes Human genes 0.000 claims description 61
108090000790 Enzymes Proteins 0.000 claims description 61
108010011485 Aspartame Proteins 0.000 claims description 59
239000000605 aspartame Substances 0.000 claims description 59
229960003438 aspartame Drugs 0.000 claims description 59
238000000034 method Methods 0.000 claims description 53
238000004519 manufacturing process Methods 0.000 claims description 51
125000006239 protecting group Chemical group 0.000 claims description 36
230000003301 hydrolyzing effect Effects 0.000 claims description 29
-1 mercaptomethoxycarbonyl (Fmoc) group Chemical group 0.000 claims description 23
230000007062 hydrolysis Effects 0.000 claims description 19
238000006460 hydrolysis reaction Methods 0.000 claims description 19
125000005629 sialic acid group Chemical group 0.000 claims description 19
238000004458 analytical method Methods 0.000 claims description 15
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 12
238000004587 chromatography analysis Methods 0.000 claims description 12
150000001412 amines Chemical class 0.000 claims description 11
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 8
229960001230 asparagine Drugs 0.000 claims description 8
235000009582 asparagine Nutrition 0.000 claims description 8
239000007788 liquid Substances 0.000 claims description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
230000002414 glycolytic effect Effects 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 claims description 5
210000003296 saliva Anatomy 0.000 claims description 4
150000008163 sugars Chemical class 0.000 claims description 4
239000000047 product Substances 0.000 claims description 3
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
206010039424 Salivary hypersecretion Diseases 0.000 claims 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
238000004040 coloring Methods 0.000 claims 1
239000000413 hydrolysate Substances 0.000 claims 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
208000026451 salivation Diseases 0.000 claims 1
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 150
239000000243 solution Substances 0.000 description 90
238000006243 chemical reaction Methods 0.000 description 88
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QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
230000000704 physical effect Effects 0.000 description 47
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USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
239000005695 Ammonium acetate Substances 0.000 description 24
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239000007864 aqueous solution Substances 0.000 description 24
239000011734 sodium Substances 0.000 description 24
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JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 19
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229940125904 compound 1 Drugs 0.000 description 14
238000005481 NMR spectroscopy Methods 0.000 description 13
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DQJCDTNMLBYVAY-ZXXIYAEKSA-N (2S,5R,10R,13R)-16-{[(2R,3S,4R,5R)-3-{[(2S,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5-(ethylamino)-6-hydroxy-2-(hydroxymethyl)oxan-4-yl]oxy}-5-(4-aminobutyl)-10-carbamoyl-2,13-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazaheptadecan-1-oic acid Chemical compound NCCCC[C@H](C(=O)N[C@@H](C)C(O)=O)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@@H](C)NC(=O)C(C)O[C@@H]1[C@@H](NCC)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](NC(C)=O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DQJCDTNMLBYVAY-ZXXIYAEKSA-N 0.000 description 10
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XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 10
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229940125961 compound 24 Drugs 0.000 description 10
239000006173 Good's buffer Substances 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
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SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 8
SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 8
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 7
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