19-Hydroxy-5β,19-cyclosteroids: synthesis, isomerization and ring opening
1997
19(R/S)-Hydroxy-5β,19-cyclosteroids
have been synthesised from the 19-formyl 4-en-3-one by reductive
cyclization with zinc in aqueous acetic acid. Treatment of the aldehyde
with lithium in liquid ammonia also gave the
19(R)-hydroxy-5β,19-cyclosteroid together with
the 17β-hydroxy analogue. The 19(R)-alcohol is
isomerized to the 19(S)-alcohol in either dilute acidic or
basic media via the 3-hydroxy-3,5-cyclosteroid. The
19(S)-alcohol is in equilibrium with its 3-hemiketal.
Treatment
of the 19(R)-alcohol with methanolic HCl gave the
19(R)- and 19(S)-methyl ethers, the 3-methyl ether
19-ketal and the
3α-methoxy-3β,5β-
cyclosteroid. Further rearrangements of the 19(R)- and
19(S)-alcohols take place on more vigorous treatment with acid
or base to give cyclopropanol ring-opened aldehydes including a
5β-methyl-A-norsteroid. Metal hydride reduction of the
3-ketone in the 19(R)-alcohol gave only the
3β-alcohol whereas the 19(S)-alcohol gave both
the 3α- and 3β-alcohols. Acid treatment of
the 3β-alcohols gave products with retention of
configuration at C-5 and C-19 while base-catalysed ring opening gave
inversion at C-5. Ring opening mainly involved breaking of the
5,19-bond, however, the 19(S)-alcohol also resulted in
10,19-bond cleavage. Structures were established by NMR
measurements.
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