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Largzole,which was recently isolated in scarce amounts by Luesch and co-workers from cyanobacteria of the genus Symploca,exhibits potent antiproliferative activity and preferentially targets cancer cells over nontransformed cells.previous studies by our group shows the replacement of valine with tyrosine in largazole increased selectivity toward human cancer cells over human normal cells more than 100-fold.Therefore to characterize largazoles structural requirements for histone deacetylase (HDAC) inhibitory and antiproliferative activities,a series of analogues with replacement of valine were prepared and biological evaluation is under way.