A concise total synthesis of the TMC-95A and TMC-95B proteasome inhibitors
Date
2004
Authors
Albrecht, Brian Keith, author
Williams, Robert M., advisor
Journal Title
Journal ISSN
Volume Title
Abstract
A concise total synthesis of the TMC-95A/B proteasome inhibitors is presented. The synthesis features the use of an L-serine derived E-selective modified Julia olefination reaction that ultimately controls the stereochemical outcome of the highly oxidized tryptophan fragment. A diastereoselective dihydroxylation, a Suzuki coupling, macrocyclization and cis-propenyl amide formation were also employed. In the process of the total synthesis, a suitable intermediate was converted to a late stage intermediate in the Danishefsky total synthesis, effectively completing a formal synthesis. The limited use of protecting groups allowed for an efficient route that is amenable to the preparation of a variety of analogs due to its convergency.
Description
Rights Access
Subject
Protease inhibitors
Ubiquitin