Applications of Zr-catalyzed carbomagnesation and Mo-catalyzed macrocyclic ring closing metathesis in asymmetric synthesis. Enantioselective total synthesis of Sch 38516 (fluvirucin B-1)

被引:128
作者
Xu, ZM [1 ]
Johannes, CW [1 ]
Houri, AF [1 ]
La, DS [1 ]
Cogan, DA [1 ]
Hofilena, GE [1 ]
Hoveyda, AH [1 ]
机构
[1] BOSTON COLL,DEPT CHEM,MERKERT CHEM CTR,CHESTNUT HILL,MA 02167
关键词
D O I
10.1021/ja972191k
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The first enantioselective total synthesis of antifungal agent Sch 38516, also known as fluvirucin B-1, is described. The synthesis includes a convergent asymmetric preparation of amine 17 and acid 18, which are then united to afford diene 62. Metal-catalyzed transformations play a crucial role in the synthesis of the latter moiety. Of particular note are the diastereo-and enantioselective Zr-catalyzed alkylations, a tandem Ti-and Ni-catalyzed process that constitutes a hydrovinylation reaction, and a Ru-catalyzed alcohol oxidation to afford carboxylic acid 18. The requisite carbohydrate 38 is synthesized in a highly diastereo-and enantioselective fashion. Optical purity of the carbohydrate moiety arises from the use of the asymmetric dihydroxylation method of Sharpless; diastereochemical control is achieved through a selective dipolar [3 + 2] cycloaddition with a readily available amine serving as the chiral auxiliary. Union of the appropriately outfitted carbohydrate 71 and diene 62 through an efficient and diastereoselective glycosylation is followed by a remarkably efficient Mo-catalyzed macrocyclization that proceeds readily at room temperature.
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页码:10302 / 10316
页数:15
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