Structure and Activity of Largazole, a Potent Antiproliferative Agent from the Floridian Marine Cyanobacterium <i>Symploca</i> sp.

TLDR

Largazole (1) possesses densely assembled unusual structural features, including a rare 4‑methylthiazoline fused to a thiazole in its cyclic core and a previously undescribed 3‑hydroxy‑7‑mercaptohept‑4‑enoic acid unit incorporated in an ester, thioester, and amide framework. Its planar structure was elucidated by 1D and 2D NMR spectroscopy with mass spectrometry, and its absolute configuration was determined by chemical degradation followed by chiral HPLC analysis. Largazole (1), a novel cytotoxic cyclodepsipeptide isolated from Symploca sp.

Abstract

A novel cytotoxic cyclodepsipeptide, termed largazole (1), has been isolated from the marine cyanobacterium Symploca sp. collected in the Florida Keys. Its planar structure was elucidated by 1D and 2D NMR spectroscopy in conjunction with mass spectrometry. The absolute configuration of 1 was determined by chemical degradation followed by chiral HPLC analysis. Largazole (1) possesses densely assembled unusual structural features, including a rare 4-methylthiazoline linearly fused to a thiazole in its cyclic core and a hitherto undescribed 3-hydroxy-7-mercaptohept-4-enoic acid unit incorporated in an ester, thioester, and amide framework. Largazole (1) exhibits potent antiproliferative activity and preferentially targets cancer cells over nontransformed cells.