Open AccessConcise Synthesis and Antimicrobial Evaluation of the Guanidinium Alkaloid Batzelladine D: Development of a Stereodivergent Strategy
Author(s) -
You-Chen Lin,
Aubert Ribaucourt,
Yasamin Moazami,
Joshua G. Pierce
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.0c04091
Subject(s) - chemistry , pyrrolidine , stereochemistry , combinatorial chemistry , antimicrobial , bicyclic molecule , modular design , enantioselective synthesis , chemical synthesis , lactam , organic chemistry , catalysis , biochemistry , in vitro , computer science , operating system
Herein, we describe a stereodivergent route to (±)-batzelladine D ( 2 ), (+)-batzelladine D ( 2 ), (-)-batzelladine D ( 2 ), and a series of stereochemical analogues and explore their antimicrobial activity for the first time. The concise synthetic approach enables access to the natural products in a sequence of 8-12 steps from readily available building blocks. Highlights of the synthetic strategy include gram-scale preparation of a late stage intermediate, pinpoint stereocontrol around the tricyclic skeleton, and a modular strategy that enables analogue generation. A key bicyclic β-lactam intermediate not only serves as the key controlling element for pyrrolidine stereochemistry but also serves as a preactivated coupling partner to install the ester side chain. The stereocontrolled synthesis allowed for the investigation of the antimicrobial activity of batzelladine D, demonstrating promising activity that is more potent for non-natural stereoisomers.