Asymmetric Synthesis of Functionalized trans-Cyclopropoxy Building Block for Grazoprevir
| Autor: | Feng Xu, Matthew D. Truppo, Hongming Li, Zhiguo J. Song, Yong-Li Zhong, Rebecca T. Ruck, Richard Desmond, Ji Qi, Tao Wang, Guy R. Humphrey, Jeonghan Park |
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| Rok vydání: | 2017 |
| Předmět: |
chemistry.chemical_classification
010405 organic chemistry Stereochemistry Organic Chemistry Enantioselective synthesis Alkyne 010402 general chemistry 01 natural sciences Biochemistry 0104 chemical sciences chemistry Grazoprevir Yield (chemistry) Intramolecular force Block (telecommunications) SN2 reaction Physical and Theoretical Chemistry Enantiomeric excess |
| Zdroj: | Organic Letters. 19:5880-5883 |
| ISSN: | 1523-7052 1523-7060 |
| DOI: | 10.1021/acs.orglett.7b02867 |
| Popis: | A practical and asymmetric synthesis of a functionalized trans-cyclopropoxy building block for the preparation of the HCV NS3/4a protease inhibitor grazoprevir is reported. Intramolecular SN2 displacement–ring closure, followed by a Baeyer–Villiger oxidation, yields the desired trans-cyclopropanol with full control of diastereoselectivity. A terminal alkyne is then effectively installed using LiNH(CH2)2NEt2. Starting from (S)-epichlorohydrin, the cyclopropoxy building block is prepared in 51% overall yield with >99.8% optical purity without isolation of any intermediates. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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