An Approach to the Synthesis of a Hepatitis C Virus Inhibitor through a Proline-Catalyzed 1,3-Dipolar Cycloaddition Using Acrolein

Synthesis ◽  
2021 ◽  
Author(s):  
Luisa Carrillo ◽  
Jose L. Vicario ◽  
Iratxe Ugarriza ◽  
Efraím Reyes ◽  
Liher Prieto ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
Virus Inhibitor

AbstractAn efficient and easy protocol for performing 1,3-dipolar cycloaddition using azomethine ylides and acrolein is presented. The reaction catalyzed by d-proline allows the synthesis of C-3 unsubstituted pyrrolidines. The application of this methodology to the synthesis of an advanced intermediate in the preparation of a Hepatitis C virus inhibitor is presented. Final attempts to complete the synthesis of the target inhibitor results in the preparation of its C-4 epimer in good overall yield.

scholarly journals Dual chiral silver catalyst in the synthetic approach to the core of hepatitis C virus inhibitor GSK 625433 using enantioselective 1,3-dipolar cycloaddition of azomethine ylides and electrophilic alkenes

2017 ◽  
Vol 28 (10) ◽  
pp. 1423-1429 ◽  
Author(s):  
Ihssene Chabour ◽  
Luis M. Castelló ◽  
Juan Mancebo-Aracil ◽  
María Martín-Rodríguez ◽  
María de Gracia Retamosa ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
Synthetic Approach ◽  
Silver Catalyst ◽  
Virus Inhibitor ◽  
The Core

scholarly journals Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

2011 ◽  
Vol 7 ◽  
pp. 988-996 ◽  
Author(s):  
María Martín-Rodríguez ◽  
Carmen Nájera ◽  
José M Sansano ◽  
Abel de Cózar ◽  
Fernando P Cossío
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Total Synthesis ◽  
Enantioselective Synthesis ◽  
Dipolar Cycloaddition ◽  
Silver Complexes ◽  
Reaction Conditions ◽  
Coulombic Interaction ◽  
Virus Inhibitor ◽  
Step Procedure

The synthesis of a GSK 2nd generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

scholarly journals Crystal Structure of a Benzimidazole Hepatitis C Virus Inhibitor Free and in Complex with the Viral RNA Target

2013 ◽  
Vol 43 (5) ◽  
pp. 235-239 ◽  
Author(s):  
Sergey M. Dibrov ◽  
Matthew A. Parker ◽  
B. Mikael Bergdahl ◽  
Thomas Hermann
Keyword(s):  
Crystal Structure ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Rna ◽  
Virus Inhibitor

The discovery and characterization of a novel scaffold as a potent hepatitis C virus inhibitor

2016 ◽  
Vol 52 (16) ◽  
pp. 3340-3343 ◽  
Author(s):  
Na Liu ◽  
Shiping Zhu ◽  
Xianghua Zhang ◽  
Xunkui Yin ◽  
Guoqiang Dong ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Structural Optimization ◽  
Phenotypic Screening ◽  
Virus Inhibitor ◽  
Target Characterization ◽  
Novel Scaffold

A novel anti-HCV benzothiazole scaffold was discovered by phenotypic screening. Further target characterization and structural optimization led to the identification of potent anti-HCV molecules targeting NS5A.

scholarly journals Stress stability study of simeprevir, a hepatitis C virus inhibitor, using feasible TLC-spectro-densitometry: application to pharmaceutical dosage form and human plasma

RSC Advances ◽  
2020 ◽  
Vol 10 (36) ◽  
pp. 21100-21107 ◽  
Author(s):  
Bassam Shaaban Mohammed ◽  
Amal E. Hamad ◽  
Sayed M. Derayea
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Human Plasma ◽  
Dosage Form ◽  
Direct Action ◽  
Stability Study ◽  
Pharmaceutical Dosage Form ◽  
Virus Inhibitor

Simeprevir is one of the newest direct action anti-hepatitis C drugs.

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