Chemical synthesis of 15 beta-hydroxytestosterone and its derivatives using a (4-methoxyphenyl)methyl protecting group

Steroids. 1996 Feb;61(2):58-64. doi: 10.1016/0039-128x(95)00196-w.

Abstract

Reaction of 3 beta-hydroxyandrosta-5,15-dien-17-one with 4-methoxybenzyl alcohol followed by acetylation gave mainly 15 beta-[(4-methoxyphenyl)methoxy]-17-oxoandrost-5-en-3 beta-yl acetate. This product was transformed by borohydride reduction and organosilyl derivatization into the orthogonally protected 17 beta-(dimethylthexylsiloxy)-15 beta-[(4-methoxyphenyl)methoxy]androst-5-en-3 beta-yl acetate and 17 beta-(dimethylisopropylsiloxy)-15 beta-[4-methoxyphenyl)methoxy]androst-5-en-3 beta-yl acetate. After deacetylation, these intermediates were submitted to Oppenauer oxidation and both yielded testosterone derivatives 17 beta-(dimethylthexylsiloxy)-15 beta-[(4-methoxyphenyl)methoxy]androst-4- en-3-one and 17 beta-(dimethylisopropylsiloxy)-15 beta-[(4-methoxyphenyl)- methoxy]androst-4-en-3-one. Removal of the (4-methoxyphenyl)methyl group from position 15 by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone treatment gave the partially protected derivatives 17 beta-(dimethylthexylsiloxy)-15 beta-hydroxyandrost-4-en-3-one and 17 beta-(dimethylisopropylsiloxy)-15 beta-hydroxyandrost-4-en-3-one. After acidic deprotection, the dimethylthexylsilyl derivative yielded 15 beta-hydroxytestosterone (15 beta,17 beta-dihydroxyandrost-4-en-3-one). Dimethylisopropylsilyl derivative was converted to the corresponding 15-hemisuccinate and 15-hemiglutarate (17 beta-hydroxy-3-oxoandrost-4-en-15 beta-yl 15-hemisuccinate and 15-hemiglutarate, respectively), which were designed as model haptens for immunoassay studies.

MeSH terms

  • Anisoles / chemistry*
  • Hydroxylation
  • Hydroxytestosterones / chemical synthesis*
  • Molecular Structure

Substances

  • Anisoles
  • Hydroxytestosterones
  • anisyl alcohol
  • 15-hydroxytestosterone