Concise Synthesis of 4'-Modified Thymidines via 1,5-Hydrogen Atom Transfer/Intermolecular 1,4-Addition Process.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI:10.1248/cpb.c25-00021

Yuta Ito, Kang Juri, Yasufumi Fuchi, Yoshiyuki Hari

引用次数: 0

Abstract

A concise approach is presented for preparing 4'-modified thymidines from oxime imidates using readily generated 4'-carbon radicals. This method produces 4'-modified thymidines from natural thymidine using the Mitsunobu reaction, the protection of 3'-hydroxy group (when necessary), and 1,5-hydrogen atom transfer (1,5-HAT)/intermolecular 1,4-addition with electron-deficient olefins. Moreover, using a one-pot synthesis involving 1,5-HAT/intermolecular 1,4-addition, followed by the hydrolysis of the imidate intermediate under basic conditions, 4'-modified thymidine was diastereoselectively isolated. This is because the 4'-isomer transferred to the water layer in the work-up process.

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1,5-氢原子转移/分子间1,4加成简明合成4'-修饰胸腺嘧啶

提出了一种简明的方法，利用易于生成的4'-碳自由基从肟类拟合物制备4'-修饰胸腺嘧啶。该方法利用Mitsunobu反应、3′-羟基保护（必要时）和1,5-氢原子转移(1,5- hat)/与缺电子烯烃的分子间1,4加成，从天然胸腺嘧啶制备4′-修饰胸腺嘧啶。此外，采用1,5- hat /分子间1,4加成的一锅法合成，然后在基本条件下水解咪酯中间体，4 '修饰的胸苷嘧啶被非对映选择性地分离出来。这是因为4′-异构体在处理过程中转移到了水层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemical & pharmaceutical bulletin 医学-化学综合

CiteScore

3.20

自引率

5.90%

发文量

132

审稿时长

1.7 months

期刊介绍： The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below. Topics: Organic chemistry In silico science Inorganic chemistry Pharmacognosy Health statistics Forensic science Biochemistry Pharmacology Pharmaceutical care and science Medicinal chemistry Analytical chemistry Physical pharmacy Natural product chemistry Toxicology Environmental science Molecular and cellular biology Biopharmacy and pharmacokinetics Pharmaceutical education Chemical biology Physical chemistry Pharmaceutical engineering Epidemiology Hygiene Regulatory science Immunology and microbiology Clinical pharmacy Miscellaneous.