Synthetic methodology to prepare polysubstituted 2-aminopyrans. Synthesis of the C32–C38 subunit of immunosuppressant sanglifehrin A

Abstract

Pyranic hemiaminal synthons are present in natural and unnatural products with biological activity. Here a synthetic pathway to prepare this type of intermediates is presented. The methodology is based on three main steps: a) The [4+3] cycloaddition reaction of an α,α'-dihaloketone and a conveniently protected 2-aminofuran diene. b) Chemical modification of the resulting oxabicyclic cycloadduct and orthogonal protection of organic functions, and c) Reductive ozonolysis of the C6–C7 double bond of the modified cycloadduct to afford a pentasubstituted polyfunctionalized pyranic hemiaminal ester with up to 94% yield. When working with 2,4-dibromo-3-pentanone and 2-tert-butoxycarbonylaminofuran as starting materials, the C32–C38 subunit of immunosuppressant sanglifehrin A was obtained with excellent yield.