Total Synthesis of the Proposed Microcyclamides MZ602 and MZ568

Yi Liu; Xiangyun Zhao; Hongbo Wang; Huili Liu; Zhuyin Sui; Bingfei Yan; Yuguo Du

doi:10.1021/acs.joc.0c02541

Total Synthesis of the Proposed Microcyclamides MZ602 and MZ568

J Org Chem. 2021 Jan 1;86(1):1065-1073. doi: 10.1021/acs.joc.0c02541. Epub 2020 Dec 9.

Authors

Yi Liu¹, Xiangyun Zhao¹, Hongbo Wang², Huili Liu², Zhuyin Sui¹, Bingfei Yan¹, Yuguo Du³

Affiliations

¹ School of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China.
² Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
³ State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

PMID: 33295775
DOI: 10.1021/acs.joc.0c02541

Abstract

The first convergent total synthesis for the proposed structures of microcyclamides MZ602 (1) and MZ568 (2) has been accomplished in 11 linear steps with 12.5 and 16.8% overall yield, respectively. Key features of the syntheses include a one-pot cascade reaction to construct core Boc-l-Ile-Thz-OAllyl fragment 5, and a removable pseudoproline (Ψ^Me,Me pro) inducer assisted cyclization of thiazole-containing all-l linear peptides. The spectral data (¹H NMR, ¹³C NMR, and HRMS) of synthetic MZ602 (1) were quite similar to those of the proposed natural microcyclamide MZ602, except to an opposite sign of the optical rotation value. Surprisingly, the synthetic MZ568 (2) presented large discrepancies in characteristic spectral data from those of the reported natural product, although the absolute configuration of key intermediate 36 was unambiguously determined by single-crystal X-ray analysis in our work. These findings revealed that the proposed structures of natural microcyclamides MZ602 and MZ568 required revision.

Publication types

Research Support, Non-U.S. Gov't