A Concise Synthesis of the HCV Protease Inhibitor BILN 2061 and Its P3 Modified Analogs  

作　　者：刘德军 董径超 尹云星 马汝建 施一峰 吴颢 陈曙辉 李革 

机构地区：[1]WuXi AppTech Co.,Ltd.,288 Fute Zhong Road,Waigaoqiao Free Trade Zone,Shanghai 200131,China

出　　处：《Chinese Journal of Chemistry》2011年第7期1489-1502,共14页中国化学（英文版）

摘　　要：A concise synthesis of BILN 2061 was achieved through more efficient installation of P2 4-quinoline moiety via SN2 displacement of the β-OBs group located on the 4-hydroxyl proline intermediate, which was prepared from 4-α-hydroxyl proline analog via Mitsunobu reaction with inversion of stereochemistry. In addition, a short and practical synthesis for P3 unit is also described herein. Final assembly of four fragments for BILN 2061 was achieved with an overall yield of 58% in 4 steps from P1 to 15a. Furthermore several analogs of BILN 2061 （WX-I--WX-5） containing modifications on P3 unit were synthesized successfully using the same synthetic route as described for the parent inhibitor BILN 2061.A concise synthesis of BILN 2061 was achieved through more efficient installation of P2 4-quinoline moiety via SN2 displacement of the β-OBs group located on the 4-hydroxyl proline intermediate, which was prepared from 4-α-hydroxyl proline analog via Mitsunobu reaction with inversion of stereochemistry. In addition, a short and practical synthesis for P3 unit is also described herein. Final assembly of four fragments for BILN 2061 was achieved with an overall yield of 58% in 4 steps from P1 to 15a. Furthermore several analogs of BILN 2061 （WX-I--WX-5） containing modifications on P3 unit were synthesized successfully using the same synthetic route as described for the parent inhibitor BILN 2061.

关 键 词：hepatitis C virus （HCV） BILN 2061 SYNTHESIS 

分 类 号：S332.3[农业科学—作物遗传育种] TQ463.4[农业科学—农艺学]