A Synthesis of Jaspamide Based on 1,2-Metallate Rearrangements of α-Heteroalkenylmetal Derivatives

Jaspamide (Jasplakinolide), a marine cyclodepsipeptide, was synthesised from tripeptide fragment 4 and (2S,4E,6R,8S)-8-benzoyloxy-2,4,6-trimethylnon-4-enoic acid (3). The tripeptide fragment was prepared from β-tyrosine derivative 6, Boc-2-bromoabrine (8), and alanine. β-Tyrosine derivative 6 was prepared by asymmetric conjugate amination of methyl p-hydroxycinnamate. Bromabrine derivative 8 was prepared from tryptophan. Key steps in the synthesis of the polyketide fragment 3 include 1,2-metallate rearrangement of a metallated dihydropyran and a metallated enol carbamate derivative.

cyclodepsipeptide - Jaspamide - antifungal - 1,2-metallate rearrangement - higher order cuprate - enol carbamate