莫诺匹拉韦是已被英美等国批准使用的抗SARS-CoV-2感染的口服药物. 目前报道的莫诺匹拉韦合成方法存在诸多不足, 如反应步骤多、反应收率低、成本高等. 报道了以价格低廉的胞嘧啶核苷为起始物, 直接酰化高效率合成莫诺匹拉韦的路线. 研究发现, 在不同比例的水/四氢呋喃溶液中依次通过胞苷的羟基选择性异丁酰化和选择性2',3'位脱异丁酰基反应, 可以顺利得到5'-O-异丁酰基胞嘧啶核苷, 再通过N⁴-羟基化反应即可得到目标产物. 该方法操作简单、反应选择性高, 最终以总收率82%制备了抗新冠病毒原料药莫诺匹拉韦.

Molnupiravir is an oral drug against SARS-CoV-2 infection approved by Britain and America in 2021. Currently, the reported synthetic methods of molnupiravir have disadvantages, such as long steps, limited yield and high cost. Efficient methods for the synthesis of molnupirovir through direct acylation of low-price cytidine are developed. In different proportions of aqueous tetrahydrofuran solution, selective isobutyrylation of hydroxyl of cytidine and further 2',3'-deprotection of 2',3',5'-tri-O-isobutyrylcytidine could be realized, which successfully gave 5'-O-isobutyrylcytidine. Finally, N⁴-hydroxylation of 5'-O-isobutyrylcytidine yielded molnupirovir. Using this straightforward and high-yielding three-step approach, molnupirovir was obtained from cytidine in 82% overall yield.