方便地使用肌苷作为起始原料合成 3-脱氮嘌呤核苷（3-脱氮肌苷、3-脱氮腺苷和 3-脱氮鸟苷）。

Convenient Synthesis of 3-Deazapurine Nucleosides (3-Deazainosine, 3-Deazaadenosine and 3-Deazaguanosine) Using Inosine as a Starting Material.

机构信息

Graduate School of Pharmaceutical Science, Tokushima University, Tokushima, Japan.

出版信息

Curr Protoc. 2021 Nov;1(11):e297. doi: 10.1002/cpz1.297.

Abstract

A convenient synthetic method for preparing 3-deazapurine nucleosides (3-deazainosine, 3-deazaadenosine, and 3-deazaguanosine) from inosine via a 5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxamide (EICAR) derivative, which is a key intermediate, is described. A large-scale synthesis of an EICAR derivative starting from inosine was achieved in six steps via dinitrophenylation at the N position followed by ring opening, iodination of the resulting 5-amino group, and a palladium-catalyzed cross-coupling reaction. The resulting EICAR derivative was then converted into 3-deazainosine, 3-deazaadenosine, and 3-deazaguanosine. This route enabled us to synthesize 3-deazapurine nucleosides conveniently in good yields. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxamide (EICAR) derivative 6 Basic Protocol 2: Preparation of 3-deazapurine nucleosides 8, 11, and 14.

摘要

从肌苷出发，通过 5-乙炔基-1-β-D-核糖基-1H-咪唑-4-甲酰胺（EICAR）衍生物这一关键中间体，方便地合成 3-去氮杂嘌呤核苷（3-去氮杂肌苷、3-去氮杂腺苷和 3-去氮鸟苷）的方法描述如下。通过 N 位的二硝基苯化，随后开环、所得 5-氨基碘代以及钯催化的交叉偶联反应，从肌苷出发经 6 步反应实现了 EICAR 衍生物的大规模合成。然后，将得到的 EICAR 衍生物转化为 3-去氮杂肌苷、3-去氮杂腺苷和 3-去氮鸟苷。该路线能够以良好的收率方便地合成 3-去氮杂嘌呤核苷。© 2021Wiley Periodicals LLC. 基础方案 1：5-乙炔基-1-β-D-核糖基-1H-咪唑-4-甲酰胺（EICAR）衍生物 6 的制备基础方案 2：3-去氮杂嘌呤核苷 8、11 和 14 的制备。