Title:
【発明の名称】新規ステロイド中間体およびその製造法
Document Type and Number:
Japanese Patent JPH07503466
Kind Code:
A
Abstract:
PCT No. PCT/US93/00211 Sec. 371 Date Jul. 25, 1994 Sec. 102(e) Date Jul. 25, 1994 PCT Filed Jan. 26, 1993 PCT Pub. No. WO93/15103 PCT Pub. Date Aug. 5, 1993.Novel steroids having a 9 alpha -hydroxy or a 9 alpha -carbonate substituent can be prepared from 9 alpha -hydroxyandrostenedione and can be utilized in the synthesis of commercially valuable corticosteroids such as betamethasone. The 9 alpha -carbonates are prepared by reaction of the corresponding 9 alpha -hydroxy steroid with a sequence of excess base, trialkylsilyl chloride, alkyl haloformate and alkanol or by using excess base, alkyl haloformate and alkoxide. 9 alpha -Carbonate-17-keto compounds can be treated with lithium acetylide and a lithium salt to afford the corresponding 17 alpha -ethynyl-17 beta -hydroxy-9 alpha -carbonate. This compound is then esterified with a novel series of reagents to give the 17-ester which can be reduced the corresponding 17-allene. Oxidation of this allene to the bis-epoxide compound, followed by treatment with an alkali metal salt of a carboxylic acid under phase transfer conditions gives the 17 alpha -hydroxy 21-ester 9 alpha -carbonate. Elimination of the 9 alpha -carbonate group affords the a 17 alpha -hydroxy, 9(11)ene, which in a few subsequent steps can be converted to a variety of commercially important corticosteroids. Novel 9 alpha -carbonate compounds are prepared in the various reaction steps.
Inventors:
Andrews, David Earl
Sudankar, Ananza Earl
Sudankar, Ananza Earl
Application Number:
JP51325593A
Publication Date:
April 13, 1995
Filing Date:
January 26, 1993
Export Citation:
Assignee:
SCHERING CORPORATION
International Classes:
A61P31/04; C07J1/00; C07J5/00; C07J7/00; C07J13/00; A61K31/57; C07J21/00; C07J31/00; C07J41/00; C07J43/00; C07J51/00; (IPC1-7): C07J5/00; A61K31/57; C07J7/00; C07J21/00; C07J43/00
Attorney, Agent or Firm:
Kyozo Yuasa (6 people outside)