Ahlqvist Grace P, McGeough Catherine P, Senanayake Chris, Armstrong Joseph D, Yadaw Ajay, Roy Sarabindu, Ahmad Saeed, Snead David R, Jamison Timothy F
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
TCG GreenChem, Inc., Process R&D Center at Princeton South, 701 Charles Ewing Boulevard, Ewing, New Jersey 08628, United States.
ACS Omega. 2021 Apr 8;6(15):10396-10402. doi: 10.1021/acsomega.1c00772. eCollection 2021 Apr 20.
Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for the treatment of COVID-19. Herein, we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on a decagram scale: the first step at 200 g and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.
莫努匹拉韦（MK-4482，EIDD-2801）是一种有前景的口服生物可利用药物，用于治疗新冠肺炎。在此，我们描述了一种以供应为中心且无需色谱法的从胞苷合成莫努匹拉韦的方法，该方法包括两个步骤：选择性酶促酰化，然后进行转氨反应以得到最终药物产品。这两个步骤均已成功在十克规模上进行：第一步为200克，第二步为80克。总体而言，莫努匹拉韦的总分离产率为41%，而专利路线中的最高分离产率为17%。该路线相对于专利文献中描述的初始路线具有许多优势，并且如果在正在进行的临床试验中证明安全有效，将降低这种药物的成本。
