A Novel Strategy for Total Solid-Phase Synthesis of Kahalalide A Derivatives

摘要

@@ Kahalalide compounds, cyclic depsipeptides isolated from a Hawaiian herbivorous marine species of sacoglossan mollusk, Elysia rufescens[1], exhibit a diverse spectrum of biological activities, including antimicrobial and antitumor activity[2]. Among them, kahalalide A (structure see Figure 1) shows anti-mycobacterial tuberculosis activity[3]. It has a novel mechanism of action and can't induce drug resistance. However, isolation and purification of kahalalides from natural resources are difficult to meet with the need of bioactivity evaluation and drug screening. Recently, Line Bourel et al. Have reported a chemical route to generate kahalalide A and its analogues[4]. Based on our previous enormous work on synthesis of cyclic peptides, a novel facile method for synthesis of kahalalide A was designed and carried out in our laboratory by a route of total solid-phase synthesis with Fmoc chemistry adaptable for preparation of kahalalide A derivatives.