Synthesis of Belactosin A Analogs

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Date
2014-06-20
Authors
Dawson Cole, Kara Anne
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Publisher
Middle Tennessee State University
Abstract
There is continuing interest in new research on cancer as well as new cancer drugs. Belactosin A, discovered in 1999, is a naturally occurring 26S proteasome inhibitor with anti-tumor activity. The 26S proteasome is a novel anti-tumor target with only two inhibitors on the market. The structure of belactosin A contains a cyclopropyl amine linked to a A-lactone. While several syntheses have been reported, only a few analogs have been prepared and analogs are needed since belactosin A is toxic.
Approaches to the synthesis of alanine cyclopropyl analogs as well as the synthesis of a simple beta-lactone are reported here. The synthetic route included a nitrocyclopropanation as well as a transfer hydrogenation to afford the core cyclopropyl amine of the analogs. Issues regarding the type of protecting group used on the "left side" of the analogs as well as attempts toward the removal of the ketone have been investigated. Attempts to couple the monoamine to the beta-lactone as well as the stability of the beta-lactone have been studied as well.
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Keywords
Belactosin A, Nitrocyclopropanation, Peptidomimetics, Synthesis
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