Belactosin A is an anti-tumor proteasome inhibitor isolated from Streptomyces that has promising activity against colon cancer and pancreatic cancer.  The novel mechanism of action makes this an interesting target, and several approaches have been reported.   A key structural feature is an aminocyclopropyl amino acid.  A general approach has been developed in our laboratory toward the synthesis of nitrocyclopropyl peptidomimetics from various protected amino acids.  Addition of bromonitromethane to enones derived from amino acids affords nitrocyclopropyl ketones in good yields, but with little stereoselectivity.  A summary of results for six amino acids is reported.  Conversion of Cbz-L-serine to a cyclopropyl intermediate that is suitable for further elaboration to belactosin A is also reported.

Synthesis of nitrocyclopropyl peptidomimetics and application to synthesis of belactosin A

245th National Meeting (2013)

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