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Zur Konfiguration des Vitamin‐D 3 ‐Metaboliten 25, 26‐Dihydroxycholecalciferol: Synthese von (25 S ,26)‐ und (25 R ,26)‐Dihydroxycholecalciferol
Author(s) -
Barner Richard,
Hübscher Josef,
Daly John J.,
Schönholzer Peter
Publication year - 1981
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19810640328
Subject(s) - chemistry , vitamin d and neurology , steroid , metabolite , stereochemistry , stigmasterol , ring (chemistry) , absolute configuration , cholecalciferol , vitamin , crystal structure , methylene , medicinal chemistry , crystallography , organic chemistry , endocrinology , medicine , biochemistry , chromatography , hormone
Configuration of the Vitamin‐D 3 ‐Metabolite 25,26‐Dihydroxycholecalciferol: Synthesis of (25 S ,26)‐ and (25 R ,26)‐Dihydroxycholecalciferol For selective synthesis of the title compounds, (25 S )‐ 1b and (25 R )‐ 1b (Scheme 1) , the protected cholesterol precursors (25 S )‐ 6 and (25 R )‐ 6 were prepared from stigmasterol‐derived steroid‐units 4a‐d and C 5 ‐side chain building blocks 5a–d by Grignard ‐ or Wittig ‐coupling (Scheme 2) , the configuration at C(25) of the target compounds being already present in the C 5 ‐units. Conversion of the cholesterol intermediates to the corresponding vitamin‐D 3 derivatives was carried out via the 7,8‐didehydrocholesterol compounds (25 S )‐ 2b and (25 R )‐ 2b (Scheme 1) , using the established photochemical‐thermal transformation of the 5,7‐diene system to the seco ‐triene system of cholecalciferol. The configuration at C(25) of the cholesterol precursors as assigned on basis of the known configuration of the C 5 ‐units used, was found to be in agreement with the result of a single crystal X‐ray analysis on compound 11 . The configuration at C(25) remained untouched on conversion of the cholesterol ring system to the seco ‐triene system of vitamin D 3 as evident from comparison of the lanthanide‐induced CD. Cotton effects observed for (25 S )‐ 3b and (25 S ) 1b . 25,26‐Dihydroxycholecalciferol observed as a natural vitamin‐D 3 metabolite has (25 S )‐configuration.