通过钯催化反应实现 DMTr 保护的 5-碘-2'-脱氧尿苷的 Suzuki-Miyaura 偶联、Heck 烯丙基化和酰胺化。

Suzuki-Miyaura Coupling, Heck Alkenylation, and Amidation of DMTr-Protected 5-Iodo-2'-Deoxyuridine via Palladium-catalyzed Reactions.

机构信息

Institute of Chemical Technology, Matunga, Mumbai, India.

Department of Chemistry, Institute of Chemical Technology, Indian Oil Odisha Campus Bhubaneswar, Odisha, India.

出版信息

Curr Protoc. 2022 Jul;2(7):e502. doi: 10.1002/cpz1.502.

DOI:10.1002/cpz1.502

PMID:35895086

Abstract

Modification of nucleosides via cross-coupling processes has been carried out extensively on unprotected halonucleosides to produce functionalized nucleosides that are often developed for incorporation into oligonucleotides or used as fluorescent probes. This approach requires protection of the 5'-OH with the 4,4'-dimethoxytrityl (DMTr) group, which is complicated and a common cause of reaction failure. Here we report a method for direct functionalization of 5'-O-DMTr-5-iodo-2'-deoxyuridine via Suzuki-Miyaura cross-coupling, Heck alkenylation, and carboamidation. This approach facilitates rapid synthesis of a variety of C5-substituted 5'-O-DMTr-2'-deoxyuridine derivatives. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of the SerrKap palladacycle complex Basic Protocol 2: Suzuki-Miyaura coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine using SerrKap palladacycle Basic Protocol 3: Heck coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine using SerrKap palladacycle Basic Protocol 4: Heck coupling of 5'-O-DMTr-5-iodo-2'-deoxyuridine with Ruth linker using Pd(OAc) /PTABS Basic Protocol 5: Carbonylative amidation of 5'-O-DMTr-5-iodo-2'-deoxyuridine using Pd(OAc) /PTABS.

摘要

通过交叉偶联过程对未保护的卤代核苷进行核苷修饰，以生成常用于寡核苷酸掺入或用作荧光探针的功能化核苷。该方法需要用 4,4'-二甲氧基三苯甲基 (DMTr) 基团保护 5'-OH，这很复杂，也是反应失败的常见原因。在这里，我们报告了一种通过 Suzuki-Miyaura 交叉偶联、Heck 烯基化和碳酰胺化直接官能化 5'-O-DMTr-5-碘-2'-脱氧尿苷的方法。该方法有利于快速合成各种 C5 取代的 5'-O-DMTr-2'-脱氧尿苷衍生物。© 2022 威利父子公司。基本方案 1：SerrKap 钯配合物的合成基本方案 2：使用 SerrKap 钯配合物进行 5'-O-DMTr-5-碘-2'-脱氧尿苷的 Suzuki-Miyaura 偶联基本方案 3：使用 SerrKap 钯配合物进行 5'-O-DMTr-5-碘-2'-脱氧尿苷的 Heck 偶联基本方案 4：使用 Pd(OAc)/PTABS 进行 5'-O-DMTr-5-碘-2'-脱氧尿苷与 Ruth 接头的 Heck 偶联基本方案 5：使用 Pd(OAc)/PTABS 进行 5'-O-DMTr-5-碘-2'-脱氧尿苷的羰基酰胺化。