Synthetic studies on the phorboxazoles: a short synthesis of an epi-C23 tetrahydropyran core

Studies on the synthesis of the anticancer natural products, the phorboxazoles, have led to the synthesis of the C21-C32 penta-substituted tetrahydropyran core which is epimeric to the natural product at C23. The synthesis was achieved in only seven linear steps. The key steps were the use of a Masamune-Abiko anti-aldol reaction, the formation of a dihydropyran precursor molecule by the use of a new 'Maitland-Japp-like' cyclisation, and a highly diastereoselective reductive alkylation of the dihydropyran double bond, to generate the corresponding tetrahydropyran ring in an excellent yield. (C) 2010 Elsevier Ltd. All rights reserved.