Phenylahistin, a Small Dipeptidic Colchicine-Like Anti-Microtubule Agent: Total Synthesis and SAR Study of the Derivatives
Phenylahistin (1), a fungal metabolite from Aspergillus ustus NSC-F038, belongs to a new class of peptidic colchicine-like microtubule-binding agents that exhibits cytotoxic activity against a wide variety of tumor cell lines . (-)-Phenylahistin (-)-1, a diketopiperazine derivative, consists of L-phenylalanine and a unique isoprenylated dehydrohistidine residue with a quaternary carbon at the 5-position of the imidazole ring. To develop more potent anti-tumor agents based on this diketopiperazine derivative, it is important to elucidate the structural components necessary for the anti-microtubule activity of (-)-1. The total synthesis of 1 will establish the synthetic route for its derivatives.
KeywordsSynthetic Route Imidazole Ring Total Synthesis Aromatic Amino Acid Residue High Cytotoxic Activity