A SYNTHESIS OF JASPAMIDE BASED ON 1,2-METALATE REARRANGEMENTS OF ALPHA-HETEROALKENYLMETAL DERIVATIVES

Jaspamide (Jasplakinolide), a marine cyclodepsipeptide, was synthesise d from tripeptide fragment 4 and :4E,6R,8S)-8-benzoyloxy-2,4,6-trimeth ylnon-4-enoic acid (3). The tripeptide fragment was prepared from beta -tyrosine derivative 6, Boc-2-bromoabrine (8), and alanine. beta-Tyros ine derivative 6 was prepared by asymmetric conjugate amination of met hyl p-hydroxycinnamate. Bromabrine derivative 8 was prepared from tryp tophan. Key steps in the synthesis of the polyketide fragment 3 includ e 1,2-metallate rearrangement of a metallated dihydropyran and a metal lated enol carbamate derivative.