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Synthesis of 4′-Thionucleoside Analogues Bearing a C2′ Stereogenic All-Carbon Quaternary Center.
- Source :
-
Molecules . Apr2024, Vol. 29 Issue 7, p1647. 26p. - Publication Year :
- 2024
-
Abstract
- The design of novel 4′-thionucleoside analogues bearing a C2′ stereogenic all-carbon quaternary center is described. The synthesis involves a highly diastereoselective Mukaiyama aldol reaction, and a diastereoselective radical-based vinyl group transfer to generate the all-carbon stereogenic C2′ center, along with different approaches to control the selectivity of the N-glycosidic bond. Intramolecular SN2-like cyclization of a mixture of acyclic thioaminals provided analogues with a pyrimidine nucleobase. A kinetic bias favoring cyclization of the 1′,2′-anti thioaminal furnished the desired β-D-4′-thionucleoside analogue in a 7:1 ratio. DFT calculations suggest that this kinetic resolution originates from additional steric clash in the SN2-like transition state for 1′,4′-trans isomers, causing a significant decrease in their reaction rate relative to 1′,4′-cis counterparts. N-glycosylation of cyclic glycosyl donors with a purine nucleobase enabled the formation of novel 2-chloroadenine 4′-thionucleoside analogues. These proprietary molecules and other derivatives are currently being evaluated both in vitro and in vivo to establish their biological profiles. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 29
- Issue :
- 7
- Database :
- Academic Search Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 176597698
- Full Text :
- https://doi.org/10.3390/molecules29071647