Belactosin A is a naturally occurring proteasome inhibitor with potent anti-tumor activity.  Activity is conferred by enzymatic acylation of the beta-lactone.  Several syntheses have been reported, however only a few analogs have been prepared.  An approach to the synthesis of analogs is reported here, with the key step being the nitrocyclopropanation of an amino-acid derived enone.  Efforts to improve stereoselectivity in the cyclopropanation are reported here.   Reduction of the nitro group, followed by coupling to a beta-lactam affords belactosin A analog which may have improved stability over the beta-lactone.  The use of alanine, phenylalanine, leucine and valine as starting materials leads to methyl, benzyl and isobutyl and isopropyl analogs of the natural product.<br/>

Synthesis of beta-lactam analogs of belactosin A<br />

249th National Meeting (2015)

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