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Description:
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The recently isolated bacterial metabolites , belactosins A -C from a fermentation
broth of Streptomyces sp . UCK14 , uniquely contain a β -lactone dipeptide motif and
exhibit anticancer activities . The enantioselective synthesis of ( - ) -belactosin C and
derivatives was accomplished in a concise manner employing the tandem , Mukaiyama
aldol -lactonizaton (TMAL ) process and test their bioactivities . . One approach involved
a distal double diastereoselective TMAL reaction with a dipeptide glyoxamide , whereas
a second approach involved amide coupling of a dipeptide with a β -lactone carboxylic
acid , obtained via the TMAL process employing a chiral silyl ketene acetal . Enzymatic
assays showed that the belactosins act as the dual inhibitors of the proteasome and the
thioesterase domain of fatty acid synthase .
Spongiolactone which uniquely contains a cyclopentyl -fused β -lactone was
isolated in 1986 from Spongi -onellagracilis No biological activity have been reported
for this compound ; however , the acylating potential of the resident β -lactone warrants
screening for potential activity . After many setbacks in the synthesis of spongiolactone ,
significant progress has been made . Importantly , NCAL process also enabled a concise construction of [3 .2 .0] -bicyclo β -lactone , which is the key structure in the
spongiolactone synthesis and only a few steps remained to complete the synthesis . |