Synthesis of migrastatin and its macroketone analogue and in vivo FRAP analysis of the macroketone on E-cadherin dynamics

Abstract

An efficient and scalable synthesis of a key acyclic intermediate used for the preparation of migrastatin and its macroketone analogue is described; Brown alkoxyallylation is the key step for this synthesis. The macroketone was prepared on 100 mg scale by this route. Treatment of invasive pancreatic cancer cells grown on a cell-derived matrix or as subcutaneous tumours in nude mice with the macroketone inhibited E-cadherin dynamics in a manner consistent with increased cell adhesion and reduced invasive potential.

Keywords: E-cadherin; antiproliferation; cell adhesion; cell-migration inhibitors; photobleaching.