ASYMMETRIC-SYNTHESIS OF CALYCULIN-C .2. SYNTHESIS OF THE C-26-C-37 FRAGMENT AND MODEL WITTIG COUPLINGS

We report our synthesis of the C-26-C-37 fragment of serine/threonine protein phosphatase PP1 and PP2A inhibitor calyculin C (1). Outlined i n this paper are synthetic approaches to the two components based on d isconnection at the C-33-N-3 amide bond. We report the successful synt hesis of the C-33-C-37 aza-sugar derived from D-lyxose which was coupl ed onto a C-26-C-32 aminooxazole originating from L-pyroglutamic acid. Elaboration of the resulting amide to a fully deprotected C-26-C-37 f ragment of calyculin C completed our synthesis. This provided an appro priate phosphonium salt for use in a Wittig olefination for joining bo th halves of the natural product.