| Autor: |
Tan L, Li D, Wan B, Niki R. Patel, Eric B. Sirota, Xu F, Varsolona Rj, Qi J, Wyvratt Bm, Song Zj, Kuethe Jt, Muzzio Dj, Qiao Z, Chen Y, Yingju Xu, Shang G, Dropinski Jf, Zhang S, Gregory Hughes, Mathew R, Zhao R, Justin A. Newman, Christopher C. Nawrat, Ouyang H, Rummelt Sm, Yin J, Margelefsky E, Kevin M. Maloney |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
The unnatural, alkyne-containing nucleoside analog islatravir (MK-8591) is synthetically accessed through a biocatalytic cascade starting from 2-ethynylglycerol as a building block. Herein, we describe the development of an efficient synthesis of this building block including the initial route, route scouting and final process development. Key challenges that have been overcome are the development of an efficient and safe acetylenic nucleophile addition to an appropriate ketone, and the identification of a 2-ethynylpropane-1,2,3-triol derivative with favorable physical properties. An acid-catalyzed cracking of commercially available 1,3-dihydroxyacetone dimer and subsequent 1,2-addition of an acetylenic nucleophile has been discovered and optimized into the manufacturing process |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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