从胞苷出发，迈向一种用于研究性COVID-19抗病毒药物莫努匹拉韦的实用非酶促工艺：以供应为中心的合成。
Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis.
作者信息
Gopalsamuthiram Vijayagopal, Kadam Appasaheb L, Noble Jeffrey K, Snead David R, Williams Corshai, Jamison Timothy F, Senanayake Chris, Yadaw Ajay K, Roy Sarabindu, Sirasani Gopal, Gupton B Frank, Burns Justina, Cook Daniel W, Stringham Rodger W, Ahmad Saeed, Krack Rudy
机构信息
Medicines for All Institute, 737 N 5th Street, Box 980100, Richmond, Virginia 23298, United States.
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
出版信息
Org Process Res Dev. 2021 Dec 17;25(12):2679-2685. doi: 10.1021/acs.oprd.1c00219. Epub 2021 Dec 9.
A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purification procedures are improved in comparison to our earlier study as all intermediates can be isolated via recrystallization. The key steps in the synthesis, namely, ester formation, hydroxyamination, and deprotection were carried out on a multigram scale to afford molnupiravir in 36-41% yield with an average purity of 98 wt % by qNMR and 99 area% by HPLC.
本文描述了一种从胞苷出发可扩展的合成莫努匹拉韦的四步方法。该方法的吸引人之处在于其完全化学合成的性质，使用了廉价的试剂以及更环保的溶剂，如水、异丙醇、乙腈和丙酮。与我们早期的研究相比，分离和纯化程序得到了改进，因为所有中间体都可以通过重结晶进行分离。合成中的关键步骤，即酯的形成、羟基胺化和脱保护，都是在多克规模上进行的，以36 - 41%的产率得到莫努匹拉韦，通过定量核磁共振（qNMR）测得平均纯度为98 wt%，通过高效液相色谱（HPLC）测得面积百分比为99%。
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