Synthesis and Late-Stage Modification of (-)-Doliculide Derivatives Using Matteson's Homologation Approach.

(-)-Doliculide, a marine cyclodepsipeptide derived from the Japanese sea hare, Dolabella auricularia , exhibits potent cytotoxic properties, sparking interest in the field of synthetic chemistry. It is comprised of a peptide segment and a polyketide moiety, rendering it amenable to Matteson's homologation methodology. This technique facilitates the diversification of the distinctive polyketide side chain, thereby permitting the introduction of functional groups in late stages for modifications of the derived compounds and studies on structure-activity relationships.