Abstract
Alkylation of malonamic esters provides a direct approach to derivatives of suberoylanilide hydroxamic acid (SAHA) that are branched at the amide carbon atom, a location pivotal for enhancing biological and therapeutic activity. Alkylations use NaH in THF followed by addition of the ester of 6-bromohexanoic acid; no protection of the amidic NH group is necessary. By this means, carboxylic acid, ester, amide, hydroxymethyl and 2-benzimidazolyl branching units have been appended to the SAHA backbone. Routes to vary one of the branching units at a time have been developed.
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