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Total Synthesis and Biological Evaluation of the Fab‐Inhibitory Antibiotic Platencin and Analogues Thereof
Author(s) -
Leung Gulice Y. C.,
Li Hao,
Toh QiaoYan,
Ng Amelia M.Y.,
Sum Rong Ji,
Bandow Julia E.,
Chen David Y.K.
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201001281
Subject(s) - intramolecular force , chemistry , stereocenter , stereochemistry , total synthesis , selectivity , antibiotics , intramolecular reaction , combinatorial chemistry , enantioselective synthesis , organic chemistry , catalysis , biochemistry
In this article, application of the masked o ‐benzoquinone intramolecular Diels–Alder reaction in the total synthesis of platencin ( 2 ), a recently reported Fab inhibitory antibiotic, is described. Through intelligence gathering, the evolving strategies ultimately culminated in three syntheses of the tricyclic core structure 11 of platencin ( 2 ). The influence of the remote stereocenter(s) in the diastereoselectivity of the intramolecular Diels–Alder reaction was investigated, together with a remarkable additive effect in drastically improving the diastereoselectivity of the intramolecular Diels–Alder reaction of the dienone 17 . The synthetic technology developed was further applied to the preparation of rationally designed analogues, based on the hypothesized FabF/FabH selectivity model. Antibacterial studies of platencin ( 2 ) and of the synthesized analogues 3 – 9 against a panel of normal and resistant strains are also reported.
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