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Synthesis of 21‐(3‐Methylbutyl)cholest‐5‐ene‐3β,3′,25‐triol and 21‐(2‐Methylpropoxy)cholest‐5‐ene‐2′,3β,25‐triol, the First “Double Side Chain” Cholesterol Analogues
Author(s) -
KurekTyrlik Alicja,
Makaeva Fliur Z.,
Wicha Jerzy,
Calverley Martin J.
Publication year - 1997
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199719970928
Subject(s) - chemistry , ene reaction , side chain , triol , alkylation , cholestane , bromide , alcohol , stereoselectivity , chain (unit) , double bond , steroid , stereochemistry , cholesterol , magnesium bromide , medicinal chemistry , organic chemistry , diol , magnesium , catalysis , hormone , biochemistry , physics , astronomy , polymer
The 21‐(3‐hydroxy‐3‐methylbutyl)‐ and 21‐(2‐hydroxy‐2‐methylpropoxy)cholestane derivatives 3 and 5 , formally double chain hybrid (20 R )‐ and (20 S )‐cholesterol analogues, were synthesized. The C‐22 to C‐27 section of the 25‐hydroxycholestane side chain was established by stereoselective alkylation with 5‐bromo‐2‐methyl‐2‐(triethylsilyl)oxypentane of the pregnanoic ester 8 , derived from 3β‐acetoxyandrost‐5‐en‐17‐one ( 7 ). Reduction of the ester 9 to the 21‐alcohol 10 permitted elaboration of a second hydroxylated side chain, either via the tosylate 11 by alkynation/hydrogenation (yielding intermediate 13 ) or by alkylation of 10 with bromoacetate (yielding 14 ) followed by reaction with methyl magnesium bromide.