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Keywords:

  • biosynthesis;
  • cytotoxin;
  • formal synthesis;
  • Mukaiyama aldol;
  • natural product

Abstract

The synthesis of a putative biosynthetic precursor of psymberin including a formal synthesis of the natural product is described. The key step towards the densely functionalized tetrahydropyran core was an enantioselective catalytic Mukaiyama aldol reaction using a titanium(IV)–BINOL catalyst system. syn-Selective reduction followed by ozonolysis led to a rapid assembly of the tetrahydropyran ring. This flexible approach also allows the synthesis of similar fragments of other complex molecules such as bryostatins and pederins. The syn-selective coupling between the tetrahydropyran and the aromatic aldehyde was achieved using a boron-mediated aldol reaction which was followed by further transformations to complete the synthesis of the precursor as well as the formal synthesis of the natural product.