Synthesis of modified miuraenamides – the Ugi approach

Abstract

Miuraenamides, a group of marine cyclodepsipeptides, closely related to jasplakinolide and geodiamolide are found to accelerate nucleation and polymerization of actin, and therefore interfere with cell division processes, at concentrations in the low nanomolar range. For SAR studies derivatives are synthesized via Ugi reaction, which provides the complete tripeptide fragment in only one step. While a wide range of modifications are possible at the C-terminus of the peptide, variations at the central position are not tolerated. Neither modifications in the polyketide.