Progess towards the total synthesis of the antifungal natural product (-)-pramanicin

Unrestricted Progress towards the total synthesis of the antifungal natural product (-)-pramanicin and efficient synthesis of its side chain, (E)-4,5-epoxy-2-tetradecenoic acid, are reported. (-)-Pramanicin consists of a functionalized lipophilic side chain bound to a chiral gamma-lactam head group. The key synthetic steps include: (i) oxygen-promoted palladium-catalyzed cross-coupling of an aliphatic alkenyl-boron compound with methyl acrylate, (ii) stereo- and regioselective monoepoxidation of the resultant diene, (iii) rhodium(II)-catalyzed intramolecular C-H insertion of an alpha-diazoacetamide to afford a bicyclic gamma-lactam, and (iv) lithium diisopropylamide promoted condensation of an alpha,beta-unsaturated, gamma,delta-epoxy aldehyde with the bicyclic gamma-lactam.