Intramolecular cyclisation routes to cyclopenta[14,15]-19-norsteroids

Abstract

14-Allyl-3-methoxy-14β-estra-1,3,5(10),15-tetraen-17-one 1 undergoes competitive Wacker oxidation at C-2′ and C-3′ to give the 14β-formylethyl and 14β-acetonyl Δ¹⁵-17-ketones 2 and 3 respectively. Alkaline treatment of 3 results in efficient intramolecular Michael reaction, and chemoselective modification of the resultant pentacyclic diketone 6 gives rise to novel cyclopenta[14,15] analogues 11 and 12 of estradiol. Low-temperature reaction of 3 with lithium hexamethyldisilazide–cerium(III) chloride furnishes mainly the product of intramolecular aldol reaction, and hence, the derived 14β,17β-propanoestra-1,3,5(10),15-tetraene-3,17β-diol 21. Alternative routes to 11 and 12, via intramolecular reductive cyclisation of the 14β-formylethyl Δ¹⁵-17-ketone 2, are described.