Synthesis of 17β-steroidal 4-(2-butenolides)

Abstract

Derivatives of 5-androsten-3β-ol with 2-butenolide ring in position 17β were prepared by addition of lithium salt of protected propargyl alcohol to 17β-carbaldehyde IV, hydrogenation of the formed isomeric acetylenes over P-2 nickel and oxidative cyclization of the obtained olefinic 20,24-diols IX and X. Stereochemistry of the desired lactones XII and XIII was determined by CD spectroscopy. The 17β-(2-furyl) derivative XI was formed as the cyclization side-product. The 3β-hydroxyl was protected by a methoxymethyl group which allowed a selective removal of tetrahydropyranyl group during the synthesis.