Chemical synthesis of 15 beta-hydroxytestosterone and its derivatives using a (4-methoxyphenyl)methyl protecting group.
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.
Cerný
I
I
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague.
Fajkos
J
J
Pouzar
V
V
D000840:Anisoles / Q000737:chemistry*; D006900:Hydroxylation; D006915:Hydroxytestosterones / Q000138:chemical synthesis*; D015394:Molecular Structure
D000840:Anisoles; D006915:Hydroxytestosterones; C066943:anisyl alcohol; C035390:15-hydroxytestosterone