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

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.

Keywords

• alotamide
• asymmetric synthesis
• relative structural determination