ES2102322A1 - Process for the preparation of didemnine A - Google Patents

Process for the preparation of didemnine A

Info

Publication number
ES2102322A1
ES2102322A1 ES09501411A ES9501411A ES2102322A1 ES 2102322 A1 ES2102322 A1 ES 2102322A1 ES 09501411 A ES09501411 A ES 09501411A ES 9501411 A ES9501411 A ES 9501411A ES 2102322 A1 ES2102322 A1 ES 2102322A1
Authority
ES
Spain
Prior art keywords
didemnine
boc
coupling
preparation
product
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.)
Granted
Application number
ES09501411A
Other languages
Spanish (es)
Other versions
ES2102322B1 (en
Inventor
Lledo Ernest Giralt
Palomera Fernando Albericio
Paul Lloyud-Williams
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.)
Pharmamar SA
Original Assignee
Pharmamar SA
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
Application filed by Pharmamar SA filed Critical Pharmamar SA
Priority to ES09501411A priority Critical patent/ES2102322B1/en
Publication of ES2102322A1 publication Critical patent/ES2102322A1/en
Application granted granted Critical
Publication of ES2102322B1 publication Critical patent/ES2102322B1/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

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

Abstract

Process for the preparation of didemnine A Comprises: (a) coupling the units Z-N(Me)-O(Me)-Tyr-O- [Boc-Thr]-OH and H-Ist-Hip-Leu-Pro-OBzl. HCl in the presence of HBTU and DIEA, (b) simultaneously deprotecting the N- and C-terminal ends of the product obtained, (c) cyclizing the product from stage (b) using the coupling agent HBTU in the presence of HOBT and DIEA to produce a macrocycle with the terminal N of the Thr protected, (d) deprotecting the said group and coupling the macrocycle with Boc-(R)-NMe-Leu-OH to produce Boc- didemnine A, (e) reacting the latter product with trifluoroacetic acid to obtain didemnine A. Didemnine A has application as an antitumour, antiviral and immunosuppressive agent.
ES09501411A 1995-07-13 1995-07-13 DIDEMNINE PREPARATION PROCEDURE A. Expired - Fee Related ES2102322B1 (en)

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 true ES2102322A1 (en) 1997-07-16
ES2102322B1 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)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002002596A3 (en) * 2000-06-30 2002-05-23 Pharma Mar Sa Synthetic methods for aplidine and new antitumoral derivatives, methods of making and using them
US7348311B2 (en) 1989-09-29 2008-03-25 Pharma Mar, S.A. Derivatives of dehydrodidemnin B
US7381703B2 (en) 2003-03-12 2008-06-03 Dana-Faber Cancer Institute, Inc. Aplidine for multiple myeloma treatment
US7507766B2 (en) 2000-10-12 2009-03-24 Pharma Mar, S.A. Treatment of cancers
US7576188B2 (en) 2003-03-12 2009-08-18 Pharma Mar, S.A.U. Antitumoral treatments
US7651997B2 (en) 2000-04-07 2010-01-26 The Trustees Of The University Of Pennsylvania Deoxo-proline-containing tamandarin and didemnin analogs, dehydro-proline-containing tamandarin and didemnin analogs, and methods of making and using them
US7737114B2 (en) 2000-04-07 2010-06-15 The Trustees Of The University Of Pennsylvania Didemnin analogs and fragments and methods of making and using them
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
US8420130B1 (en) 1998-02-18 2013-04-16 Pharma Mar S.A. Pharmaceutical formulation of a didemnin compound
US10538535B2 (en) 2017-04-27 2020-01-21 Pharma Mar, S.A. Antitumoral compounds

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991004985A1 (en) * 1989-09-29 1991-04-18 Pharma Mar S.A. Dehydrodidemnin b
WO1993000362A1 (en) * 1991-06-20 1993-01-07 Basf Aktiengesellschaft New peptides (didemnins), their preparation and their use

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991004985A1 (en) * 1989-09-29 1991-04-18 Pharma Mar S.A. Dehydrodidemnin b
WO1993000362A1 (en) * 1991-06-20 1993-01-07 Basf Aktiengesellschaft New peptides (didemnins), their preparation and their use

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7348311B2 (en) 1989-09-29 2008-03-25 Pharma Mar, S.A. Derivatives of dehydrodidemnin B
US8420130B1 (en) 1998-02-18 2013-04-16 Pharma Mar S.A. Pharmaceutical formulation of a didemnin compound
US7737114B2 (en) 2000-04-07 2010-06-15 The Trustees Of The University Of Pennsylvania Didemnin analogs and fragments and methods of making and using them
US7651997B2 (en) 2000-04-07 2010-01-26 The Trustees Of The University Of Pennsylvania Deoxo-proline-containing tamandarin and didemnin analogs, dehydro-proline-containing tamandarin and didemnin analogs, and methods of making and using them
US7348310B2 (en) 2000-06-30 2008-03-25 Pharma Mar, S.A. Synthetic methods for aplidine and new antitumoral derivatives, methods of making and using them
CZ304204B6 (en) * 2000-06-30 2014-01-02 Pharma Mar, S. A. Aplidine derivatives
WO2002002596A3 (en) * 2000-06-30 2002-05-23 Pharma Mar Sa Synthetic methods for aplidine and new antitumoral derivatives, methods of making and using them
US7678765B2 (en) 2000-06-30 2010-03-16 Pharma Mar, S.A. Synthetic methods for aplidine and new antitumoral derivatives, methods of making and using them
US7507766B2 (en) 2000-10-12 2009-03-24 Pharma Mar, S.A. Treatment of cancers
US7576188B2 (en) 2003-03-12 2009-08-18 Pharma Mar, S.A.U. Antitumoral treatments
US7381703B2 (en) 2003-03-12 2008-06-03 Dana-Faber 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
US10538535B2 (en) 2017-04-27 2020-01-21 Pharma Mar, S.A. Antitumoral compounds
US11332480B2 (en) 2017-04-27 2022-05-17 Pharma Mar, S.A. Antitumoral compounds
US11339180B2 (en) 2017-04-27 2022-05-24 Pharma Mar, S.A. Antitumoral compounds
US11713325B2 (en) 2017-04-27 2023-08-01 Pharma Mar, S.A. Antitumoral compounds

Also Published As

Publication number Publication date
ES2102322B1 (en) 1998-03-01

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