SYNTHESIS OF 1,3-DIOL SYNTHONS FROM EPOXY AROMATIC PRECURSORS - AN APPROACH TO THE CONSTRUCTION OF POLYACETATE-DERIVED NATURAL-PRODUCTS

被引:100
作者
EVANS, DA
GAUCHETPRUNET, JA
CARREIRA, EM
CHARETTE, AB
机构
[1] Department of Chemistry, Harvard University, Cambridge
关键词
D O I
10.1021/jo00002a048
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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 beta-keto ester synthons. Birch reduction [GRAPHICS] of 9 (R = Si(i)Pr3) followed by ozonolysis afforded the hydroxyl keto ester 11 in 66% overall yield. Anti-selective beta-selective beta-hydroxy ketone reduction employing Me4NBH(OAc)3 afforded 12 in 93% yield and 13:1 diastereoselectivity while syn-selective reduction with Et2BOMe/NaBH4 gave 13 in 82% 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 (93% yield, > 99:1) by Mitsunobu inversion followed by methanolysis. This reaction sequence provides access to all stereoisomers of 3,5,6-trihydroxyhexanoic acid hepatonic acids which should be useful chiral subunits of polyacetate-derived natural products such as amphotericin and bryostatin.
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页码:741 / 750
页数:10
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