Synthetic approach to 5 alpha-pregnanolone 19-[O-(carboxymethyl)oxime] derivatives

Syntheses of 5alpha-pregnanolone derivatives (3-hydroxy-5alpha-pregnan-20-ones) with 3alpha- and 3beta-configuration and 19-[O-(carboxymethyl)oxime] group were developed, starting from 19-hydroxy-20-oxopregn-5-en-3beta-yl acetate. After catalytic hydrogenation, acetylation and ketone protection, the...

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Published inCollection of Czechoslovak chemical communications Vol. 69; no. 9; pp. 1805 - 1817
Main Authors Cerny, Havlikova, H, Hill, M, Hampl, R, Pouzar
Format Journal Article
LanguageEnglish
Published PRAGUE 6 Inst Organic Chem And Biochem 01.01.2004
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
synthesis
haptens
RAT
neurosteroids
hormones
ALLOPREGNANOLONE
3-ALPHA-HYDROXY-5-ALPHA-PREGNAN-20-ONE
O-(carboxymethyl)oxime
oximes
RADIOIMMUNOASSAY
PLASMA
NEUROACTIVE STEROIDS
steroids
PARTURITION
PREGNANOLONE ISOMERS
PRECURSORS
BRAIN
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Summary:Syntheses of 5alpha-pregnanolone derivatives (3-hydroxy-5alpha-pregnan-20-ones) with 3alpha- and 3beta-configuration and 19-[O-(carboxymethyl)oxime] group were developed, starting from 19-hydroxy-20-oxopregn-5-en-3beta-yl acetate. After catalytic hydrogenation, acetylation and ketone protection, the acetyl in position 3 was removed. To obtain the 3alpha- derivative, nitrite epimerization of the intermediate tosylate was performed before the introduction of methoxymethyl protecting group, while the 3beta-derivative was protected directly. In both series, deacetylation, oxidation to an aldehyde and O-(carboxymethyl) hydroxylamine condenzation followed. Conversion to the methyl ester, simultaneous deprotection of positions 3 and 20, and alkaline hydrolysis gave the corresponding 19-[ O-(carboxymethyl) oximes]. The nine- and ten-step syntheses described herein (yields 19.5 and 7.3%, respectively) gave the target compounds, designed as haptens for immunological use.
ISSN:0010-0765
DOI:10.1135/cccc20041805