2. Academic Validation
  3. Synthesis of Nucleosides and Deoxynucleosides via Gold(I)-Catalyzed N-Glycosylation of Glycosyl (Z)-Ynenoates

Synthesis of Nucleosides and Deoxynucleosides via Gold(I)-Catalyzed N-Glycosylation of Glycosyl (Z)-Ynenoates

  • Org Lett. 2022 Dec 30;24(51):9479-9484. doi: 10.1021/acs.orglett.2c03964.
Rongkun Liu 1,  Yan Chen 1,  Jibin Zheng 1,  Lvfeng Zhang 1,  Tong Xu 1,  Peng Xu 2,  You Yang 1
Affiliations

Affiliations

  • 1 Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
  • 2 State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
PMID: 36524759 DOI: 10.1021/acs.orglett.2c03964
Abstract

Nucleoside analogues are widely used as Anticancer and Antiviral drugs. Here, we develop a highly efficient gold(I)-catalyzed N-glycosylation approach for versatile synthesis of various types of nucleosides and deoxynucleosides with glycosyl (Z)-ynenoates as donors. The wide scope of the N-glycosylation approach was demonstrated by the synthesis of 31 pyrimidine nucleosides and 8 purine nucleosides. Remarkably, the gold(I)-catalyzed N-glycosylation of pyranosyl (Z)-ynenoates with purines was found to be very effective for regioselective synthesis of pyranosyl N9 purine nucleosides. Based on the catalytic N-glycosylation approach, convenient synthesis of two 5'-deoxynucleosides drugs (capecitabine and galocitabine), four 2'-deoxynucleoside drugs (floxuridine, trifluridine, decitabine and cladribine), four 3',5'-dideoxynucleoside analogues, and four 2',5'-dideoxynucleoside analogues was achieved in a collective manner.

Figures
Products