Title:
INTERMEDIATES AND REACTION SEQUENCE TO PRODUCE SAID INTERMEDIATES USEFUL FOR THE PREPARATION OF ANTINEOPLASTIC AND ANTIFUNGAL CRYPTOPHYCIN DERIVATIVES
Document Type and Number:
WIPO Patent Application WO2000034253
Kind Code:
A3
Abstract:
A process for preparing a compound of the formula (I) wherein G is (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl, or Ar; Ar is an aromatic or heteroaromatic group or a substituted aromatic or heteroaromatic group; R<3> is (C1-C6) alkyl; R is trityl or a suitable silyl protecting group; R is hydrogen or a suitable carboxy protecting group; and LG is a suitable hydroxy activating group; or a pharmaceutically acceptable salt thereof, useful in the preparation of cryptophycin derivatives. The processes involve an asymmetric crotylboration and, in the preferred embodiment, a subsequent asymmetric allylboration, providing for an efficient method for preparing Fragment A of the cryptophycin molecule. Also disclosed are novel intermediates useful for preparing cryptophycin compounds.
Inventors:
DHOKTE ULHAS PRABHAKAR
KHAU VIEN VAN
MARTINELLI MICHAEL JOHN
KHAU VIEN VAN
MARTINELLI MICHAEL JOHN
Application Number:
PCT/US1999/028497
Publication Date:
November 16, 2000
Filing Date:
December 02, 1999
Export Citation:
Assignee:
LILLY CO ELI (US)
UNIV HAWAII (US)
UNIV WAYNE STATE (US)
UNIV HAWAII (US)
UNIV WAYNE STATE (US)
International Classes:
C07D273/00; (IPC1-7): C07D273/08; C07D413/06; C07F5/02; C07F7/08
Domestic Patent References:
| WO1998008812A1 | 1998-03-05 |
Foreign References:
| EP0861838A2 | 1998-09-02 |
Other References:
KECK G.E. ET AL.: "Synthetic studies on the Rhizoxins. II. An approach to the C10-C26 subunit using substrate directed allylstannane additions to aldehydes", TETRAHEDRON LETTERS, NL, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, vol. 37, no. 19, 6 May 1996 (1996-05-06), pages 3291 - 3294, XP002089413, ISSN: 0040-4039
TOSHIMA K. ET AL.: "Total synthesis of Bafilomycin A1", JOURNAL OF ORGANIC CHEMISTRY, US, AMERICAN CHEMICAL SOCIETY, EASTON, vol. 62, no. 10, 16 May 1997 (1997-05-16), pages 3271 - 3284, XP002138900
GARDINIER K.M. & LEAHY J.W.: "Enantiospecific total synthesis of the potent antitumor macrolides Cryptophycins 1 and 8", JOURNAL OF ORGANIC CHEMISTRY, US, AMERICAN CHEMICAL SOCIETY, EASTON, vol. 62, no. 21, 17 October 1997 (1997-10-17), pages 7098 - 7099, XP002138901
MICALIZIO G.C. & ROUSH W.R.: "Towards the synthesis of Spongistatin 1: Diastereoselective synthesis of the C(36)-C(45) subunit", TETRAHEDRON LETTERS, NL, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, vol. 40, no. 17, 23 April 1999 (1999-04-23), pages 3351 - 3354, XP004162280, ISSN: 0040-4039
MULZER J. ET AL.: "Felkin-Anh-selective Hiyama addition to O-protected lactaldehydes: A general solution to the Blastmycinone stereoproblem", JOURNAL OF ORGANIC CHEMISTRY, US, AMERICAN CHEMICAL SOCIETY, EASTON, vol. 53, no. 17, 19 August 1988 (1988-08-19), pages 4098 - 4103, XP000909710
TOSHIMA K. ET AL.: "Total synthesis of Bafilomycin A1", JOURNAL OF ORGANIC CHEMISTRY, US, AMERICAN CHEMICAL SOCIETY, EASTON, vol. 62, no. 10, 16 May 1997 (1997-05-16), pages 3271 - 3284, XP002138900
GARDINIER K.M. & LEAHY J.W.: "Enantiospecific total synthesis of the potent antitumor macrolides Cryptophycins 1 and 8", JOURNAL OF ORGANIC CHEMISTRY, US, AMERICAN CHEMICAL SOCIETY, EASTON, vol. 62, no. 21, 17 October 1997 (1997-10-17), pages 7098 - 7099, XP002138901
MICALIZIO G.C. & ROUSH W.R.: "Towards the synthesis of Spongistatin 1: Diastereoselective synthesis of the C(36)-C(45) subunit", TETRAHEDRON LETTERS, NL, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, vol. 40, no. 17, 23 April 1999 (1999-04-23), pages 3351 - 3354, XP004162280, ISSN: 0040-4039
MULZER J. ET AL.: "Felkin-Anh-selective Hiyama addition to O-protected lactaldehydes: A general solution to the Blastmycinone stereoproblem", JOURNAL OF ORGANIC CHEMISTRY, US, AMERICAN CHEMICAL SOCIETY, EASTON, vol. 53, no. 17, 19 August 1988 (1988-08-19), pages 4098 - 4103, XP000909710
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