Synthesis of novel macrolactam and macroketone analogues of migrastatin from D-glucal and comparison with macrolactone and acyclic analogues: A dorrigocin A congener is a potent inhibitor of gastric cancer cell migration

摘要

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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).