Synthetic Studies on Spiroketal Natural Products. IV.A Stereoselective Synthesis of (3S, 5S, 6R, 9R, R_S)-3-Benzyloxymethyl-9-hydroxymethyl-5-(p-tolyl)sulfinyl-1, 7-dioxaspiro[5.5]undecane, a Key Intermediate for Talaromycins

Abstract

A dioxaspiro compound (4), a common intermediate for the synthesis of talaromycin A (1) and (-)-talaromycin B (2), was synthesized by two routes utilizing two kinds of asymmetric recognition of prochiral 1, 3-diols controlled by sulfinyl chirality, that is, firstly by acid promoted diastereoselective C-O bond fission of the bicyclic acetal (7) to give the dihydropyran derivative (6), which has an S-hydroxymethyl group at the C3-position (7→6), and secondly by diastereoselective intramolecular Michael addition of the diol (5), in which the three chiral centers at C5, C6, C9 were constructed in one step (5→4).