Synthetic Studies toward (−)-Cleistenolide: Highly Stereoselective Synthesis of New γ-Lactone Subunits

This study describes the stereoselective synthesis of two new γ -lactones in 6 and 3 steps and 19 and 32% yield, respectively, directed toward the total synthesis of the natural product ( − )-cleistenolide. The starting material was an enantiomerically pure diacetonide diol, derived from d-mannitol with the required stereocenters for ( − )-cleistenolide synthesis. γ -Lactone syntheses were based on highly selective protection and deprotection of hydroxyls from d-mannitol. The formation of γ -lactone rings was the culmination of this approach, made possible by a Horner-Wadsworth-Emmons Z-olefination between diacetal aldehyde and ethyl 2-(bis(o-tolyloxy)phosphoryl)acetate to produce an unsaturated ester. The Z-isomer ester was highly favored in relation to the E-isomer (Z/E ratio of 94:6), allowing the formation of the γ -lactone ring under acid catalysis. This strategy precluded the use of chiral auxiliaries or catalysts for the control of stereocenters in the novel γ -lactones.
Source: Journal of the Brazilian Chemical Society - Category: Chemistry Source Type: research