Title:
PROCESSES FOR THE PRODUCTION OF (-)-TETRAHYDROLIPSTATIN AND INTERMEDIATES THEREOF
Document Type and Number:
WIPO Patent Application WO/2004/065346
Kind Code:
A1
Abstract:
Processes for the production of compounds (IV) and (VIII) and (-)-tetrahydrolipstatin (XI), characterized by subjecting a compound (III) to diastereo-selective reduction to obtain a compound (IV), subjecting the compound (IV) to hexenylation, hydrolysis, reaction with sulfonyl halide or the like, deblocking, and catalytic reduction in this order to obtain compound (VIII), and then condensing the compound (VIII) with N-formyl-L-leucine in the presence of a carbodiimide condensing agent and a tertiary amine at a reaction temperature of less than 0°C. According to the processes, (-)-tetrahydrolipstatin useful as antiobestic and useful intermediates for the synthesis thereof can be efficiently produced at high optical purity and in relatively high yields in reduced steps. (III) (IV) (VIII) (XI) (wherein P2 is a hydroxyl-protecting group; and R is alkyl having 1 to 4 carbon atoms, benzyl, or 4-nitrobenzyl)
Inventors:
WATANABE YOSUKE (JP)
IKEMOTO TETSUYA (JP)
IKEMOTO TETSUYA (JP)
Application Number:
PCT/JP2004/000400
Publication Date:
August 05, 2004
Filing Date:
January 20, 2004
Export Citation:
Assignee:
SUMIKA FINE CHEMICALS CO LTD (JP)
WATANABE YOSUKE (JP)
IKEMOTO TETSUYA (JP)
WATANABE YOSUKE (JP)
IKEMOTO TETSUYA (JP)
International Classes:
C07C67/31; C07D305/12; (IPC1-7): C07C67/31; C07B53/00; C07C69/675; C07C69/732; C07D305/12
Foreign References:
| EP1127886A1 | 2001-08-29 | |||
| US4983746A | 1991-01-08 |
Other References:
FLEMING I. ET AL: "A synthesis of (-)-tetrahydrolipstatin in which the relative stereochemistry is controlled by a phenyldimethylsilyl group", TETRAHEDRON LETTERS, vol. 31, no. 25, 1990, pages 3645 - 3648, XP002064050
FLEMING I. ET AL: "Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of (-)-tetrahydrolipstatin using the alkylation of a beta-silyl ester and the hydroboration of an allylsilane", J. CHEM. SOC. PERKIN TRANS. 1, vol. 17, 1998, pages 2679 - 2686, XP002979361
GHOSH A.K. ET AL: "A stereoselective synthesis of (-)-tetrahydrolipstatin", CHEM. COMMUN., 1999, pages 1743 - 1744, XP002979362
PARSONS P.J. ET AL: "A rapid synthesis of (-)-tetrahydrolipstatin", SYNLETT, no. 1, 2000, pages 107 - 109, XP002979363
FLEMING I. ET AL: "Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of (-)-tetrahydrolipstatin using the alkylation of a beta-silyl ester and the hydroboration of an allylsilane", J. CHEM. SOC. PERKIN TRANS. 1, vol. 17, 1998, pages 2679 - 2686, XP002979361
GHOSH A.K. ET AL: "A stereoselective synthesis of (-)-tetrahydrolipstatin", CHEM. COMMUN., 1999, pages 1743 - 1744, XP002979362
PARSONS P.J. ET AL: "A rapid synthesis of (-)-tetrahydrolipstatin", SYNLETT, no. 1, 2000, pages 107 - 109, XP002979363
Attorney, Agent or Firm:
Takashima, Hajime (1-1 Fushimimachi 4-chome, Chuo-ku, Osaka-sh, Osaka ., JP)
Download PDF: