STEREOSELECTIVE SYNTHESIS AND STRUCTURAL ESTABLISHMENT OF 5S)-24,24-DIFLUORO-1-ALPHA,25,26-TRIHYDROXYVITAMIN D-3, A MAJOR METABOLITE OF 24,24-DIFLUORO-1-ALPHA,25-DIHYDROXYVITAMIN D-3

Authors
IWASAKI H HOSOTANI R MIYAMOTO Y NAKANO Y YAMAMOTO K YAMADA S SHINKI T SUDA T YAMAGUCHI K KONNO K TAKAYAMA H
Citation
H. Iwasaki et al., STEREOSELECTIVE SYNTHESIS AND STRUCTURAL ESTABLISHMENT OF 5S)-24,24-DIFLUORO-1-ALPHA,25,26-TRIHYDROXYVITAMIN D-3, A MAJOR METABOLITE OF 24,24-DIFLUORO-1-ALPHA,25-DIHYDROXYVITAMIN D-3, Tetrahedron, 54(49), 1998, pp. 14705-14724
Citations number
23
Categorie Soggetti
Chemistry Inorganic & Nuclear
Journal title
Tetrahedron → ACNP
ISSN journal
00404020
Volume
54
Issue
49
Year of publication
1998
Pages
14705 - 14724
Database
ISI
SICI code
0040-4020(1998)54:49<14705:SSASEO>2.0.ZU;2-F
Abstract
(25S)-24,24-Difluoro-1 alpha,25,26-trihydroxyvitamin D-3 (3a) and its (25R)-epimer (3b), either of which is expected to be a major metabolit e of 24,24-difluoro-1 alpha,25-dihydroxyvitamin D-3 (2), were synthesi zed. Asymmetric addition to beta-ketosulfoxides (5a, 5b) of trimethyla luminum was used as a key process to construct the chiral tertiary alc ohol moiety of 3a and 3b. The absolute configuration of the tertiary a lcohol was determined by X-ray crystallographic analysis of 20 which i s a CD-ring analog of the 3a intermediate. The configuration at the C( 25) position of the metabolite was established as S by HPLC comparison between the metabolite and chemically synthesized 3a and 3b. (C) 1998 Elsevier Science Ltd. All rights reserved.