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Novel Protoilludane Lead Structure for Veterinary Antibiotics: Total Synthesis of Pasteurestins A and B and Assignment of Their Configurations
Author(s) -
Kögl Marion,
Brecker Lothar,
Warrass Ralf,
Mulzer Johann
Publication year - 2008
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.200800074
Subject(s) - chemistry , total synthesis , antibiotics , lead compound , tin , stereochemistry , pathogen , combinatorial chemistry , microbiology and biotechnology , organic chemistry , biochemistry , in vitro , biology
Two novel protoilludane sesquiterpenoids, named pasteurestins A and B ( 1 and 2 ), were disclosed in a recent patent. These compounds were reported to exhibit strong and selective activity against some Mannheimia haemolytica strains, pathogen causatives for bovine respiratory disease. These properties qualified 1 and 2 as potential lead structures for new veterinary antibiotics; however, neither the absolute nor the relative configurations had been determined, nor were the compounds available any longer. We thus developed total syntheses of 1 and 2 and clarified their structures and their biological profiles. Key steps were two [2+2+2] CpCo(CO) 2 ‐mediated Vollhardt cycloadditions in both syntheses, and a tin‐mediated asymmetric Reformatsky‐type condensation in the synthesis of 2 with a temperature‐dependent product distribution.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)