Total synthesis of zaragozic acid A (squalestatin S1). Synthesis of the relay compound

被引:66
作者
Caron, S [1 ]
Stoermer, D [1 ]
Mapp, AK [1 ]
Heathcock, CH [1 ]
机构
[1] UNIV CALIF BERKELEY,DEPT CHEM,BERKELEY,CA 94720
关键词
D O I
10.1021/jo961534e
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Compound 2 has been prepared from the 1,6-anhydropyranohexose 3. The key process for elaborating the 1,7-dioxabicyclo[3.2.1]octane core of the zaragozic acids is addition of an organometallic reagent to lactone 6 and treatment of the resulting 1,2,3-trihydroxy-6-oxo ethylene acetal with acid. Use of the cerium(III) reagent of 4-bromo-1-butene in this process provided 7 in excellent yield, unaccompanied by the isomeric 1,6-anhydropyranose isomer. The remaining two carboxy groups of the zaragozic acid core were added by addition of the lithium enolate of 8 to formaldehyde, to obtain 9, and cerium(III)-mediated addition of vinyllithium to ketone 10. The latter addition was shown by 2D H-1 NMR experiments to provide the relative configuration found in the zaragozic acids. Similar stereoselective additions were observed with 2-furyllithium and (5-methyl-2-furyl)-lithium, but the resulting adducts are resistant to ozonolysis. The synthesis of 2 completes a total synthesis of zaragozic acid A (squalestatin S1) (1).
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页码:9126 / 9134
页数:9
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