Synthesis of the C21–C34-segment of the aplyronines using the dimer of methylketene

This report describes a convergent synthesis of the C21–C34-segment of aplyronine. The starting point for both halves of this segment was the dimer of methylketene, readily available in either enantiomeric form by asymmetric catalysis. Diastereoselective reduction and functional group manipulation afforded the partners for a Wittig coupling reaction. The appropriate choice of oxygen protecting groups allowed the Wittig reaction to proceed, and hydrogenation of the resulting olefin afforded the C21–C34-synthon.