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A Concise Synthesis of the HCV Protease Inhibitor BILN 2061 and Its P3 Modified Analogs
Author(s) -
Liu Dejun,
Dong Jingchao,
Yin Yunxing,
Ma Rujian,
Shi Yifeng,
Wu Hao,
Chen Shuhui,
Li Ge
Publication year - 2011
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201180270
Subject(s) - chemistry , moiety , stereochemistry , yield (engineering) , proline , combinatorial chemistry , quinoline , mitsunobu reaction , amino acid , organic chemistry , biochemistry , materials science , metallurgy
A concise synthesis of BILN 2061 was achieved through more efficient installation of P2 4‐quinoline moiety via S N 2 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‐1 – WX ‐ 5 ) containing modifications on P3 unit were synthesized successfully using the same synthetic route as described for the parent inhibitor BILN 2061 .