Synthesis of 1,3-Diol Synthons from Epoxy Aromatic Precursors: An Approach to the Construction of Polyacetate-Derived Natural Products

Article abstract of DOI:10.1021/jo00002a048

The identification of stereoregular polyol subunits within polyacetate-derived natural products such as bryostatin 1 and amphotericin B has led to the convergent synthesis of six- and seven-carbon 1,3-diol fragments in high yields and stereoselectivities.This plan relies upon the enantioselective asymmetric epoxidation/kinetic resolution of cinnamyl alcohols and the use of meta-substituted anisyl rings as masked β-keto ester synthons.Birch reduction of 9 (R = SiⁱPr3) followed by ozonolysis afforded the hydroxyl keto ester 11 in 66percent overall yield.Anti-selective β-selective β-hydroxy ketone reduction employing Me4NBH(OAc)3 afforded 12 in 93percent yield and 13:1 diastereoselectivity while syn-selective reduction with Et2BOMe/NaBH4 gave 13 in 82percent yield and 15:1 diastereoselectivity.An analogous sequence of reactions provided 25 and 26 from epoxy alcohol 18.Epoxy aromatic alcohol 17 (R = H) was easily converted to 18 (93percent yield, > 99:1) by Mitsunobu inversion followed by methanolysis.This reaction sequence provides access to all stereoisomers of 3,5,6-trihydroxyhexanoic acid heptanoic acids which should be useful chiral subunits of polyacetate-derived natural products such as amphotericin and bryostatin.