Work

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

Year: 2025

Type: article

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.

Source: Chemical and Pharmaceutical Bulletin

DOI: 10.1248/cpb.c25-00021

Authors: Yuta Ito, Kang Juri, Yasufumi Fuchi, Yoshiyuki Hari

Institution: Tokushima Bunri University

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: diamond

Funder: Japan Society for the Promotion of Science

Award: Site-selective epimerization of nucleosides via 1,5-hydrogen atom transfer