Author:
Martín-Rodríguez María,Nájera Carmen,Sansano José M,de Cózar Abel,Cossío Fernando P
Abstract
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.
Cited by
31 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
1. Synthesis and Biological Activity of Potential Antiviral Compounds Through 1,3-Dipolar Cycloadditions; Part 2: Nitrones, Nitrile Oxides and Imines, and Other 1,3-Dipoles;Arkivoc;2023-01-04
2. An Approach to the Synthesis of a Hepatitis C Virus Inhibitor through a Proline-Catalyzed 1,3-Dipolar Cycloaddition Using Acrolein;Synthesis;2021-12-06
3. Stereoselective synthesis and biological evaluation as inhibitors of hepatitis C virus RNA polymerase of GSK3082 analogues with structural diversity at the 5-position;European Journal of Medicinal Chemistry;2019-06
4. Light-stable polypyridine silver(i) complexes of 1,3,5-triaza-7-phosphaadamantane (PTA) and 1,3,5-triaza-7-phosphaadamantane-7-sulfide (PTAS): significant antiproliferative activity of representative examples in aqueous media;Dalton Transactions;2019
5. Application of 1,3-Dipolar Reactions between Azomethine Ylides and Alkenes to the Synthesis of Catalysts and Biologically Active Compounds;European Journal of Organic Chemistry;2018-10-03