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 in this paper are synthetic approaches to the two components based on disconnection at the C-33-N-3 amide bond. We report the successful synthesis of the C-33-C-37 aza-sugar derived from D-lyxose which was coupled 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 fragment of calyculin C completed our synthesis. This provided an appropriate phosphonium salt for use in a Wittig olefination for joining both halves of the natural product.