Asymmetric Synthesis of the C15⁻C32 Fragment of Alotamide and Determination of the Relative Stereochemistry.

Hao-Yun Shi,Yu Gao,Yi-Hong Lu,Pei Hu,Yang Xie,Cheng-Gang Huang,Zi-Qiong Guo

doi:10.3390/md16110414

Abstract

Alotamide is a cyclic depsipetide isolated from a marine cyanobacterium and possesses a unique activation of calcium influx in murine cerebrocortical neurons (EC50 4.18 µM). Due to its limited source, the three stereocenters (C19, C28, and C30) in its polyketide fragment remain undetermined. In this study, the first asymmetric synthesis of its polyketide fragment was achieved. Four relative possible diastereomers were constructed with a boron-mediated enantioselective aldol reaction and Julia–Kocienski olefination as the key steps. Comparison of 13C NMR spectra revealed the relative structure of fragment C15–C32 of alotamide.

Highlights

Several active secondary metabolites have been isolated from marine cyanobacterium and some of these metabolites demonstrate excellent bioactivities such as cytotoxic, antimicrobial, and antiprotozoal properties [1,2]
Alotamide was isolated from the marine cyanobacterium Lyngbya bouillonii in 2009 [7]
We described the first asymmetric synthesis of its polyketide fragment

Summary

Introduction

Several active secondary metabolites have been isolated from marine cyanobacterium and some of these metabolites demonstrate excellent bioactivities such as cytotoxic, antimicrobial, and antiprotozoal properties [1,2]. Alotamide was isolated from the marine cyanobacterium Lyngbya bouillonii in 2009 [7]. It is a cyclic depsipeptide and structurally has two parts. N-Me-Val, Cys-derived thiazolene ring, and Pro and the southern part is a special unsaturated polyketide with three undetermined stereocenters (C19, C28, and C30). Given that calcium overload is involved in physiological processes and may lead to several nervous diseases such as AD and epilepsy, this compound has gained increasing attention as a new neurotoxin from the marine resource [8]. We described the first asymmetric synthesis of its polyketide fragment

Methods

Results

Conclusion