Efficient total syntheses of pumiliotoxins A and B. Applications of iodide-promoted iminium ion - Alkyne cyclizations in alkaloid construction

被引:65
作者
Lin, NH [1 ]
Overman, LE [1 ]
Rabinovitz, MH [1 ]
Robinson, LA [1 ]
Sharp, MJ [1 ]
Zablocki, J [1 ]
机构
[1] UNIV CALIF IRVINE,DEPT CHEM,IRVINE,CA 92717
关键词
D O I
10.1021/ja961641q
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A practical route for the total synthesis of pumiliotoxin A alkaloids is described. The central step is formation of the piperidine ring and establishment of the (Z)-alkylidene side chain by an iodide-promoted iminium ion-alkyne cyclization. The total synthesis of (+)-15(S)-pumiliotoxin A (2) was realized in 5 steps and 32% overall yield from alkyne 36 and epoxide 7, This synthesis of 2 proceeded in 13 steps and 12% overall yield from (S)-2-methyl-1-penten-3-ol (25) and 8 steps and 9% overall yield from N-[(benzyloxy)carbonyl]-L-proline. The synthesis of (+)-pumilioloxin B (3) was similarly achieved in four steps and 44% overall yield from alkyne 54 and epoxide 7. The overall yield of enantiopure 3 was 8% from N-[(benzyloxy)carbonyl]-L-proline and 10% from (4S,5R)-4-methyl-5-phenyl-2-oxazolidinone. These syntheses represent substantial improvement over previous routes to these important alkaloids.
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收藏
页码:9062 / 9072
页数:11
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1996, J ORG CHEM, V61, pA22