Oral Presentation 10th Australian Peptide Conference 2013

Total synthesis and biological studies of thiazole/thiazoline-containing marine peptides (#62)

Tao Ye 1
  1. Hong Kong Polytechnic University, Hong Kong

Marine cyanobacteria have produced a wide variety of peptides, many of which have demonstrated antiproliferative activity, acute cytotoxic activity, or have specific neurotoxic activity. Their diversity in both biological activity and in structural complexity has made these marine peptides the focus of much work in recent years. In a large number of marine peptides, thiazole/thiazoline heterocycles are found as key structural features. These heterocycles rigidify otherwise flexible backbones, contribute to lipophilicity, and their presence frequently correlates with DNA, RNA, and protein binding properties. The recently isolated thiazole/thiazoline-containing marine peptides included largazole, grassypeptolides, hoiamides and bisebromoamide. The small quantities of peptides that are produced by many marine cyanobacteria have proven to be a severe obstacle for the development of promising new leads for the development of novel drugs. In order to verify the primary structure proposed on the basis of studies of the marine peptides, and modify the structure, with the ultimate aim of improving activity or the physicochemical/biological properties of the lead molecule, we have undertaken extensive programs towards the synthesis of thiazole/thiazoline-containing marine natural products. The presentation will focus on two aspects:
(1) Synthetic studies towards the total synthesis of these thiazole/thiazoline-containing peptides, which included the strategic design of the synthetic approaches, problem-solving, confirmation of structures of largazole, grassypeptolides, hoiamides, and revision of stereochemistry of bisebromoamide.
(2) Biological studies of largazole and bisebromoamide in treatment of liver fibrosis through inhibition of both fibrogenesis and angiogenesis.

  1. Z. Xu, Tao Ye “Chapter 12, Thiazoline/thiazole and their derivatives” Pages: 459–505, in “Heterocycles in Natural Product Synthesis” Ed. by Majumdar & Chattopadhyay, WILEY-VCH, Verlag GmbH & Co. KGaA, Weinheim, 2011