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 calyculin C is presented. The syn methyl arrangement in 4 was established through cyclic stereocontrol. Several methods for oxidizing the intermediate oxazolines 18 and 19 to the finished oxazole fragments were explored. The best results were obtained with oxidations proceeding through the corresponding ester enolate when the carbamate NH side chain was temporarily protected with a TMS group, or with CuBr(2)/DBU/HMTA-based oxidations. The finished oxazole fragment 4 was obtained in 21% overall yield, starting from Boc-D-alaninal.