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

Abstract

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.