SYNTHESIS OF THE C-26-C-32 OXAZOLE FRAGMENT OF CALYCULIN-C - A TEST-CASE FOR OXAZOLE SYNTHESES

The synthesis of the C-26-C-32 oxazole fragment 4 and its C-32 epimer 20 of serine/threonine protein phosphatase PP1 and PP2A inhibitor caly culin C is presented. The syn methyl arrangement in 4 was established through cyclic stereocontrol. Several methods for oxidizing the interm ediate oxazolines 18 and 19 to the finished oxazole fragments were exp lored. The best results were obtained with oxidations proceeding throu gh the corresponding ester enolate when the carbamate NH side chain wa s temporarily protected with a TMS group, or with CuBr2/DBU/HMTA-based oxidations. The finished oxazole fragment 4 was obtained in 21% overa ll yield, starting from Boc-D-alaninal.