Asymmetric Synthesis of Calyculin C. 2. Synthesis of the C26−C37 Fragment and Model Wittig Couplings

We report our synthesis of the C26−C37 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 C33−N3 amide bond. We report the successful synthesis of the C33−C37 aza-sugar derived from d-lyxose which was coupled onto a C26−C32 aminooxazole originating from l-pyroglutamic acid. Elaboration of the resulting amide to a fully deprotected C26−C37 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.