Efficient solid-phase synthesis of FK228 analogues as potent antitumoral agents

Novel structural analogues of a HDAC inhibitor FK228 have been synthesized by modifying the most synthetically challenging unit, (3S,4E)-3-hydroxy-7- mercaptoheptenoic acid, with simple isosteric substitutions. These changes did not alter the backbone structure from FK228 but enabled facile and rapid synthesis by using readily available starting materials and high-yielding reactions. FK228 analogues were examined for their antitumoral activity on a variety of human cancer cells and led to the identification of new potent compounds.