RU2000115955A - INTERMEDIATE PRODUCTS AND METHODS USEFUL IN PARTIAL SYNTHESIS OF PACLITAXEL AND ITS ANALOGUES - Google Patents
INTERMEDIATE PRODUCTS AND METHODS USEFUL IN PARTIAL SYNTHESIS OF PACLITAXEL AND ITS ANALOGUESInfo
- Publication number
- RU2000115955A RU2000115955A RU2000115955/04A RU2000115955A RU2000115955A RU 2000115955 A RU2000115955 A RU 2000115955A RU 2000115955/04 A RU2000115955/04 A RU 2000115955/04A RU 2000115955 A RU2000115955 A RU 2000115955A RU 2000115955 A RU2000115955 A RU 2000115955A
- Authority
- RU
- Russia
- Prior art keywords
- group
- tert
- iii
- intermediate product
- groups
- Prior art date
Links
- RCINICONZNJXQF-MZXODVADSA-N Intaxel Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 title claims 4
- 229960001592 Paclitaxel Drugs 0.000 title claims 4
- 229930003347 taxol Natural products 0.000 title claims 4
- 230000015572 biosynthetic process Effects 0.000 title claims 3
- 238000003786 synthesis reaction Methods 0.000 title claims 3
- 230000002194 synthesizing Effects 0.000 title claims 3
- 125000004429 atoms Chemical group 0.000 claims 4
- 125000004432 carbon atoms Chemical group C* 0.000 claims 4
- -1 for example Chemical group 0.000 claims 4
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 150000001875 compounds Chemical class 0.000 claims 3
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- YWLXLRUDGLRYDR-ZHPRIASZSA-N 10-deacetylbaccatin III Natural products O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 claims 2
- OVMSOCFBDVBLFW-VHLOTGQHSA-N 5β,20-epoxy-1,7β,13α-trihydroxy-9-oxotax-11-ene-2α,4α,10β-triyl 4,10-diacetate 2-benzoate Chemical compound O([C@@H]1[C@@]2(C[C@H](O)C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)O)C(=O)C1=CC=CC=C1 OVMSOCFBDVBLFW-VHLOTGQHSA-N 0.000 claims 2
- 238000006640 acetylation reaction Methods 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 150000002917 oxazolidines Chemical class 0.000 claims 2
- 125000004665 trialkylsilyl group Chemical group 0.000 claims 2
- WASQWSOJHCZDFK-UHFFFAOYSA-N Diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 claims 1
- 230000002378 acidificating Effects 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000005466 alkylenyl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 229930014667 baccatin III Natural products 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 125000001129 phenylbutoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
Claims (10)
в котором А представляет собой группу
R1 - группа защиты гидроксила или атом водорода;
R2 - группа защиты гидроксила, выбранная из группы, состоящей из ацильных групп карбоновых кислот С1-4 (например, ацетила), триалкилсилильных групп, в которых каждая алкильная группа содержит от 1 атома до 3 атомов углерода, и группы А в соответствии с вышеприведенным определением; либо атом водорода.1. An intermediate product for use in the partial synthesis of paclitaxel containing a compound of structure
in which a represents a group
R 1 is a hydroxyl protecting group or a hydrogen atom;
R 2 is a hydroxyl protection group selected from the group consisting of acyl groups of carboxylic acids C 1-4 (for example, acetyl), trialkylsilyl groups in which each alkyl group contains from 1 atom to 3 carbon atoms, and group A in accordance with the above definition; or a hydrogen atom.
в котором R4 - арил или алкил либо алкенил линейного или разветвленного строения, содержащий от 1 атома до 5 атомов углерода; R5 - группа R4 или трет-бутоксигруппа; и каждая из групп R6 и R7 представляет собой галоидированный метил.5. An intermediate product for use in the partial synthesis of paclitaxel containing a compound of formula (III)
in which R 4 is aryl or alkyl or alkenyl of a linear or branched structure containing from 1 atom to 5 carbon atoms; R 5 is an R 4 group or a tert-butoxy group; and each of the groups R 6 and R 7 represents halogenated methyl.
(i) получение промежуточного соединения путем проведения реакции 10-деацетилбаккатина III с трет-бутоксипирокарбонатом с получением 7-трет-бутоксикарбонил-10-деацетилбаккатина III;
(ii) ацетилирование 7-трет-бутоксикарбонил-10-деацетилбаккатина III в положение 10 с получением 7-трет-бутоксикарбонилбаккатина III
(iii) введение группы
в которой R3 - группа защиты гидроксила, например, трет-бутоксикарбонил, метоксиметил, 1-этоксиэтил, бензилоксиметил, β-триалкилсилилэтоксиметил, в котором каждая алкильная группа содержит от 1 атома до 3 атомов углерода, тетрагидропиранил или 2,2,2-трихлорэтоксикарбонил; либо атом водорода, в положение 13 7-трет-бутоксикарбонилбаккатина III путем проведения реакции защищенного баккатина III с производным оксазолидина формулы (III);
в котором R4 - фенил; R5 - группа R4 или трет-бутоксигруппа; и каждая из групп R6 и R7 представляет собой галоидированный метил;
(iv) селективное отщепление групп А и R3 в кислой среде в мягких условиях с применением минеральной или органической кислоты.7. A method of producing paclitaxel, including:
(i) preparing an intermediate compound by reacting 10-deacetylbaccatin III with tert-butoxypyrocarbonate to obtain 7-tert-butoxycarbonyl-10-deacetylbaccatin III;
(ii) acetylation of 7-tert-butoxycarbonyl-10-deacetylbaccatin III to position 10 to obtain 7-tert-butoxycarbonylbaccatin III
(iii) introduction of the group
in which R 3 is a hydroxyl protection group, for example, tert-butoxycarbonyl, methoxymethyl, 1-ethoxyethyl, benzyloxymethyl, β-trialkylsilylethoxymethyl, in which each alkyl group contains from 1 atom to 3 carbon atoms, tetrahydropyranyl or 2,2,2-trichloroethoxycarbonyl ; or a hydrogen atom, at position 13 of 7-tert-butoxycarbonylbaccatin III by reacting protected baccatin III with an oxazolidine derivative of formula (III);
in which R 4 is phenyl; R 5 is an R 4 group or a tert-butoxy group; and each of the groups R 6 and R 7 represents halogenated methyl;
(iv) selective cleavage of groups A and R 3 in an acidic environment under mild conditions using a mineral or organic acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/975,804 US5917062A (en) | 1997-11-21 | 1997-11-21 | Intermediates and methods useful in the semisynthesis of paclitaxel and analogs |
| US08/975,804 | 1997-11-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2000115955A true RU2000115955A (en) | 2002-03-10 |
| RU2213739C2 RU2213739C2 (en) | 2003-10-10 |
Family
ID=25523419
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2000115955/04A RU2213739C2 (en) | 1997-11-21 | 1998-11-19 | Method for preparing paclitaxel and intermediate compounds for its partial synthesis |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US5917062A (en) |
| EP (1) | EP1049686B9 (en) |
| JP (1) | JP3445973B2 (en) |
| KR (1) | KR100545436B1 (en) |
| CN (1) | CN1229364C (en) |
| AT (1) | ATE308533T1 (en) |
| AU (1) | AU746448C (en) |
| CA (1) | CA2310778C (en) |
| CZ (1) | CZ296350B6 (en) |
| DE (1) | DE69832202T2 (en) |
| DK (1) | DK1049686T3 (en) |
| ES (1) | ES2251106T3 (en) |
| HK (1) | HK1028046A1 (en) |
| HU (1) | HUP0100375A3 (en) |
| NO (1) | NO20002600L (en) |
| PL (1) | PL192422B1 (en) |
| RU (1) | RU2213739C2 (en) |
| SI (1) | SI1049686T1 (en) |
| SK (1) | SK285797B6 (en) |
| WO (1) | WO1999026939A1 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19925926A1 (en) * | 1999-06-08 | 2000-12-14 | Bayer Ag | Catalysts based on titanium-containing, organic-inorganic hybrid materials for the selective oxidation of hydrocarbons |
| JP4502338B2 (en) * | 1999-09-17 | 2010-07-14 | 株式会社横浜国際バイオ研究所 | Method for producing taxoid compounds |
| AU775373B2 (en) | 1999-10-01 | 2004-07-29 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| IT1319682B1 (en) | 2000-12-06 | 2003-10-23 | Indena Spa | PACLITAXEL SUMMARY PROCEDURE. |
| ITMI20012185A1 (en) * | 2001-10-19 | 2003-04-19 | Indena Spa | PROCEDURE FOR THE PREPARATION OF 14BETA-HYDROXY-BACCATIN III-1,14-CARBONATE |
| ITMI20020782A1 (en) * | 2002-04-12 | 2003-10-13 | Indena Spa | SEMI-SYNTHETIC PROCESS FOR THE PREPARATION OF N-DEBENZOILPACLITAXEL |
| KR101266549B1 (en) * | 2006-10-20 | 2013-05-24 | 시노팜 싱가포르 피티이 리미티드 | Process for making crystalline anhydrous docetaxel |
| EP2358693A4 (en) * | 2008-11-20 | 2012-04-18 | Reddys Lab Ltd Dr | Preparation of docetaxel |
| PL388144A1 (en) | 2009-05-29 | 2010-12-06 | Przedsiębiorstwo Produkcyjno-Wdrożeniowe Ifotam Spółka Z Ograniczoną Odpowiedzialnością | (2R,3S)-3-tert-butoxycarbonylamino-2-hydroxy-3-phenylpropionate 4-acetoxy-2?-benzoiloxy-5� ,20-epoxy-1, 7�, 10�-trihydroxy-9-oxo-taks-11 -en-13?-yl solvates, a method for their production and application thereof |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US34277A (en) * | 1862-01-28 | Improvement in lamps | ||
| FR2601676B1 (en) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | PROCESS FOR THE PREPARATION OF TAXOL AND DESACETYL-10 TAXOL |
| FR2601675B1 (en) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | TAXOL DERIVATIVES, THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| FR2629818B1 (en) * | 1988-04-06 | 1990-11-16 | Centre Nat Rech Scient | PROCESS FOR THE PREPARATION OF TAXOL |
| USRE34277E (en) * | 1988-04-06 | 1993-06-08 | Centre National De La Recherche Scientifique | Process for preparing taxol |
| US5175315A (en) * | 1989-05-31 | 1992-12-29 | Florida State University | Method for preparation of taxol using β-lactam |
| MY110249A (en) * | 1989-05-31 | 1998-03-31 | Univ Florida State | Method for preparation of taxol using beta lactam |
| MX9102128A (en) * | 1990-11-23 | 1992-07-08 | Rhone Poulenc Rorer Sa | DERIVATIVES OF TAXANE, PROCEDURE FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITION THAT CONTAINS THEM |
| FR2678930B1 (en) * | 1991-07-10 | 1995-01-13 | Rhone Poulenc Rorer Sa | PROCESS FOR THE PREPARATION OF DERIVATIVES OF BACCATIN III AND DESACETYL-10 BACCATIN III. |
| CA2071160A1 (en) * | 1991-07-31 | 1993-02-01 | Vittorio Farina | Asymmetric synthesis of taxol side chain |
| US5229526A (en) * | 1991-09-23 | 1993-07-20 | Florida State University | Metal alkoxides |
| US5470866A (en) * | 1992-08-18 | 1995-11-28 | Virginia Polytechnic Institute And State University | Method for the conversion of cephalomannine to taxol and for the preparation of n-acyl analogs of taxol |
| FR2696460B1 (en) * | 1992-10-05 | 1994-11-25 | Rhone Poulenc Rorer Sa | Process for the preparation of taxane derivatives. |
| US5703247A (en) * | 1993-03-11 | 1997-12-30 | Virginia Tech Intellectual Properties, Inc. | 2-Debenzoyl-2-acyl taxol derivatives and methods for making same |
| CA2170661A1 (en) * | 1995-03-22 | 1996-09-23 | John K. Thottathil | Novel methods for the preparation of taxanes using oaxzolidine intermediates |
| IT1275435B (en) * | 1995-05-19 | 1997-08-07 | Indena Spa | DERIVATIVES OF 10-DESACETYL-14BETA-HYDROXYBACCATIN III, THEIR METHOD OF PREPARATION AND FORMULATIONS CONTAINING THEM |
| KR100225535B1 (en) * | 1996-08-27 | 1999-10-15 | 정지석 | Process for preparing paclitaxel |
-
1997
- 1997-11-21 US US08/975,804 patent/US5917062A/en not_active Expired - Fee Related
-
1998
- 1998-09-30 US US09/163,249 patent/US5907042A/en not_active Expired - Fee Related
- 1998-11-19 PL PL340553A patent/PL192422B1/en unknown
- 1998-11-19 SK SK732-2000A patent/SK285797B6/en unknown
- 1998-11-19 EP EP98954684A patent/EP1049686B9/en not_active Expired - Lifetime
- 1998-11-19 WO PCT/IB1998/001912 patent/WO1999026939A1/en active IP Right Grant
- 1998-11-19 DE DE69832202T patent/DE69832202T2/en not_active Expired - Fee Related
- 1998-11-19 HU HU0100375A patent/HUP0100375A3/en unknown
- 1998-11-19 AT AT98954684T patent/ATE308533T1/en not_active IP Right Cessation
- 1998-11-19 KR KR1020007005257A patent/KR100545436B1/en not_active IP Right Cessation
- 1998-11-19 CN CNB988114143A patent/CN1229364C/en not_active Expired - Fee Related
- 1998-11-19 RU RU2000115955/04A patent/RU2213739C2/en not_active IP Right Cessation
- 1998-11-19 CA CA002310778A patent/CA2310778C/en not_active Expired - Fee Related
- 1998-11-19 AU AU11705/99A patent/AU746448C/en not_active Ceased
- 1998-11-19 CZ CZ20001869A patent/CZ296350B6/en not_active IP Right Cessation
- 1998-11-19 DK DK98954684T patent/DK1049686T3/en active
- 1998-11-19 SI SI9830811T patent/SI1049686T1/en unknown
- 1998-11-19 JP JP2000522097A patent/JP3445973B2/en not_active Expired - Fee Related
- 1998-11-19 ES ES98954684T patent/ES2251106T3/en not_active Expired - Lifetime
-
2000
- 2000-05-19 NO NO20002600A patent/NO20002600L/en not_active Application Discontinuation
- 2000-11-24 HK HK00107527A patent/HK1028046A1/en not_active IP Right Cessation
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