ES2102322B1 - DIDEMNINE PREPARATION PROCEDURE A. - Google Patents
DIDEMNINE PREPARATION PROCEDURE A.Info
- Publication number
- ES2102322B1 ES2102322B1 ES09501411A ES9501411A ES2102322B1 ES 2102322 B1 ES2102322 B1 ES 2102322B1 ES 09501411 A ES09501411 A ES 09501411A ES 9501411 A ES9501411 A ES 9501411A ES 2102322 B1 ES2102322 B1 ES 2102322B1
- Authority
- ES
- Spain
- Prior art keywords
- didemnine
- boc
- coupling
- preparation procedure
- macrocycle
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title abstract 2
- 230000008878 coupling Effects 0.000 abstract 3
- 238000010168 coupling process Methods 0.000 abstract 3
- 238000005859 coupling reaction Methods 0.000 abstract 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 abstract 2
- 150000002678 macrocyclic compounds Chemical class 0.000 abstract 2
- KYHUYMLIVQFXRI-XYUQHQMCSA-N (2s)-n-[(2r)-1-[[(3s,6s,8s,12s,13r,16s,17r,20s,23s)-13-[(2s)-butan-2-yl]-12-hydroxy-20-[(4-methoxyphenyl)methyl]-6,17,21-trimethyl-3-(2-methylpropyl)-2,5,7,10,15,19,22-heptaoxo-8-propan-2-yl-9,18-dioxa-1,4,14,21-tetrazabicyclo[21.3.0]hexacosan-16-yl]amino Chemical compound CN([C@H](CC(C)C)C(=O)N[C@@H]1C(=O)N[C@@H]([C@H](CC(=O)O[C@H](C(=O)[C@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N(C)[C@@H](CC=2C=CC(OC)=CC=2)C(=O)O[C@@H]1C)C(C)C)O)[C@@H](C)CC)C(=O)[C@@H]1CCCN1C(=O)C(C)O KYHUYMLIVQFXRI-XYUQHQMCSA-N 0.000 abstract 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 abstract 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 abstract 1
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 230000000840 anti-viral effect Effects 0.000 abstract 1
- 239000003443 antiviral agent Substances 0.000 abstract 1
- 230000001351 cycling effect Effects 0.000 abstract 1
- 229930189582 didemnin Natural products 0.000 abstract 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 abstract 1
- 229940125721 immunosuppressive agent Drugs 0.000 abstract 1
- 239000003018 immunosuppressive agent Substances 0.000 abstract 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
PROCEDIMIENTO DE PREPARACION DE DIDEMNINA A. COMPRENDE: (A) ACOPLAR LAS UNIDADES Z-N(ME)-O(ME)-TYR-O[BOC-THR]-OH Y H-IST-HIP-LEU-PRO-OBZL.HCL EN PRESENCIA DE HBTU Y DIEA; (B) DESPROTEGER SIMULTANEAMENTE LOS EXTREMOS N- Y C-TERMINAL DEL PRODUCTO OBTENIDO; (C) CICLAR EL PRODUCTO DE LA ETAPA (B) EMPLEANDO EL ACOPLANTE HBTU Y EN PRESENCIA DE HOBT Y DIEA, PARA PRODUCIR UN MACROCICLO CON EL N-TERMINAL DE LA THR PROTEGIDO; (D) DESPROTEGER DICHO GRUPO Y ACOPLAR EL MACROCICLO CON BOC-(R)-NMELEU-OH PARA PRODUCIR LA BOC-DIDEMNINA A; (E) HACER REACCIONAR ESTE ULTIMO PRODUCTO CON ACIDO TRIFLUORACETICO PARA OBTENER LA DIDEMNINA A. LA DIDEMNINA A TIENE APLICACION COMO AGENTE ANTITUMORAL, ANTIVIRAL E INMUNOSUPRESOR.DIDEMNIN PREPARATION PROCEDURE A. UNDERSTANDS: (A) COUPLING UNITS ZN (ME) -O (ME) -TYR-O [BOC-THR] -OH AND H-IST-HIP-LEU-PRO-OBZL.HCL IN PRESENCE OF HBTU AND DIEA; (B) SIMULTANEOUSLY DETACH THE N- AND C-TERMINAL ENDS OF THE PRODUCT OBTAINED; (C) CYCLING THE PRODUCT FROM STAGE (B) USING THE HBTU COUPLING AND IN THE PRESENCE OF HOBT AND DIEA, TO PRODUCE A MACROCYCLE WITH THE N-TERMINAL OF THE PROTECTED THR; (D) UNPROTECT THAT GROUP AND COUPLING THE MACROCYCLE WITH BOC- (R) -NMELEU-OH TO PRODUCE BOC-DIDEMNINE A; (E) MAKE THIS LAST PRODUCT REACT WITH TRIFLUORACETIC ACID TO OBTAIN DIDEMNINE A. DIDEMNINE A IS APPLIED AS ANTITUMORAL, ANTIVIRAL AND IMMUNOSUPPRESSIVE AGENT.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES09501411A ES2102322B1 (en) | 1995-07-13 | 1995-07-13 | DIDEMNINE PREPARATION PROCEDURE A. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES09501411A ES2102322B1 (en) | 1995-07-13 | 1995-07-13 | DIDEMNINE PREPARATION PROCEDURE A. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2102322A1 ES2102322A1 (en) | 1997-07-16 |
| ES2102322B1 true ES2102322B1 (en) | 1998-03-01 |
Family
ID=8291039
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09501411A Expired - Fee Related ES2102322B1 (en) | 1995-07-13 | 1995-07-13 | DIDEMNINE PREPARATION PROCEDURE A. |
Country Status (1)
| Country | Link |
|---|---|
| ES (1) | ES2102322B1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030148933A1 (en) | 1990-10-01 | 2003-08-07 | Pharma Mar S.A. | Derivatives of dehydrodidemnin B |
| GB9803448D0 (en) | 1998-02-18 | 1998-04-15 | Pharma Mar Sa | Pharmaceutical formulation |
| IL152111A0 (en) | 2000-04-07 | 2003-07-31 | Univ Pennsylvania | Tamandarin and didemnin analogs and methods of making and using them |
| US6509315B1 (en) | 2000-04-07 | 2003-01-21 | The Trustees Of The University Of Pennsylvania | Didemnin analogs and fragments and methods of making and using them |
| UA76718C2 (en) * | 2000-06-30 | 2006-09-15 | Фарма Мар, С.А. | Anticancer aplidine derivatives |
| BR0114604A (en) | 2000-10-12 | 2003-10-14 | Pharma Mar Sa | Cancer treatment |
| CN101579520A (en) | 2003-03-12 | 2009-11-18 | 达纳-法伯癌症协会有限公司 | Aplidine for the treatment of multiple myeloma |
| WO2004080477A1 (en) | 2003-03-12 | 2004-09-23 | Dana-Farber Cancer Institute, Inc. | Aplidine for multiple myeloma treatment |
| US8030279B2 (en) | 2003-03-21 | 2011-10-04 | The Trustees Of The University Of Pennsylvania | Tamandarin analogs and fragments thereof and methods of making and using |
| JOP20190254A1 (en) | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | Antitumoral compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8922026D0 (en) * | 1989-09-29 | 1989-11-15 | Pharma Mar Sa | Novel anti-viral and cytotoxic agent |
| DE4120327A1 (en) * | 1991-06-20 | 1992-12-24 | Basf Ag | NEW PEPTIDES, THEIR PREPARATION AND USE |
-
1995
- 1995-07-13 ES ES09501411A patent/ES2102322B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ES2102322A1 (en) | 1997-07-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EC2A | Search report published |
Date of ref document: 19970716 Kind code of ref document: A1 Effective date: 19970716 |
|
| FD2A | Announcement of lapse in spain |
Effective date: 20151026 |