Atropselective macrocyclization of diaryl ether ring systems: Application to the synthesis of vancomycin model systems

被引:113
作者
Nicolaou, KC
Boddy, CNC
机构
[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
关键词
D O I
10.1021/ja020736r
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Vancomycin is the last line of defense available in the clinic for treating multidrug-resistant bacterial infections. Vancomycin contains two 16-membered diaryl ether macrocycles, each of which contains a stereogenic axis across the diaryl ether linkage. Since an effective total synthesis of vancomycin requires that these stereogenic axes be formed in a stereoselective manner, we have developed an atropselective variation of the triazene mediated diaryl ether forming reaction. This variation introduced an energetic penalty into the transition state of the undesired atropisomer. This reaction is used to synthesize the C-O-D diaryl ether macrocycle found in vancomycin with high diastereoselectivity (de > 90%), providing the naturally occurring atropisomeric configuration.
引用
收藏
页码:10451 / 10455
页数:5
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