Synthesis of Novel Macrolactam and Macroketone Analogues of Migrastatin from <scp>D</scp>‐Glucal and Comparison with Macrolactone and Acyclic Analogues: A Dorrigocin A Congener Is a Potent Inhibitor of Gastric Cancer Cell Migration

Abstract

Abstract Novel macrolactam and macroketone analogues of the migrastatin macrolide core have been synthesised from tri‐ O ‐acetyl‐ D ‐glucal in order to facilitate structure‐activity studies. The Horner olefination, followed by ring‐closing metathesis were key steps in the synthesis of the macroketone. The ability of the macroketone and macrolactam derivatives to inhibit the migration of gastric tumour cells as determined using a transwell migration assay were compared with macrolactone analogues and dorrigocin A analogues. One dorrigocin A congener was the most potent inhibitor of gastric cancer cell migration.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)