Collect. Czech. Chem. Commun. 2004, 69, 1805-1817

Synthetic Approach to 5α-Pregnanolone 19-[O-(Carboxymethyl)oxime] Derivatives

Ivan Černýa, Helena Havlíkováb, Martin Hillb, Richard Hamplb and Vladimír Pouzara,*

a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
b Institute of Endocrinology, Národní 8, 116 98 Prague 1, Czech Republic


Syntheses of 5α-pregnanolone derivatives (3-hydroxy-5α-pregnan-20-ones) with 3α- and 3β-configuration and 19-[O-(carboxymethyl)oxime] group were developed, starting from 19-hydroxy-20-oxopregn-5-en-3β-yl acetate. After catalytic hydrogenation, acetylation and ketone protection, the acetyl in position 3 was removed. To obtain the 3α-derivative, nitrite epimerization of the intermediate tosylate was performed before the introduction of methoxymethyl protecting group, while the 3β-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.

Keywords: Synthesis; Steroids; O-(Carboxymethyl)oxime; Haptens; Oximes; Neurosteroids; Hormones.

References: 25 live references.