26879-47-0Relevant articles and documents
A short de novo synthesis of nucleoside analogs
Adluri, Bharanishashank,Britton, Robert,Campeau, Louis-Charles,Cohen, Ryan,Lehmann, Johannes,Meanwell, Michael,Silverman, Steven M.,Wang, Yang
, p. 725 - 730 (2020/09/02)
Nucleoside analogs are commonly used in the treatment of cancer and viral infections. Their syntheses benefit from decades of research but are often protracted, unamenable to diversification, and reliant on a limited pool of chiral carbohydrate starting materials. We present a process for rapidly constructing nucleoside analogs from simple achiral materials. Using only proline catalysis, heteroaryl-substituted acetaldehydes are fluorinated and then directly engaged in enantioselective aldol reactions in a one-pot reaction. A subsequent intramolecular fluoride displacement reaction provides a functionalized nucleoside analog. The versatility of this process is highlighted in multigram syntheses of D- or L-nucleoside analogs, locked nucleic acids, iminonucleosides, and C2′- and C4′-modified nucleoside analogs. This de novo synthesis creates opportunities for the preparation of diversity libraries and will support efforts in both drug discovery and development.
Antifreeze protein-induced selective crystallization of a new thermodynamically and kinetically less preferred molecular crystal
Wang, Sen,Wen, Xin,Golen, James A.,Arifin, Josh F.,Rheingold, Arnold L.
, p. 16104 - 16112 (2014/04/03)
The formation of a new, dihydrate crystalline form of 5-methyluridine (m5U) was selectively induced by a protein additive, antifreeze protein (AFP) in a highly efficient manner (in 10-6molar scale, whereas known kinetic additives nee
Synthesis and anti-viral activity of a series of D- and l-2′-deoxy-2′-fluororibonucleosides in the subgenomic HCV replicon system
Shi, Junxing,Du, Jinfa,Ma, Tianwei,Pankiewicz, Krzysztof W.,Patterson, Steven E.,Tharnish, Phillip M.,McBrayer, Tamara R.,Stuyver, Lieven J.,Otto, Michael J.,Chu, Chung K.,Schinazi, Raymond F.,Watanabe, Kyoichi A.
, p. 1641 - 1652 (2007/10/03)
Based on the discovery of (2′R)-D-2′-deoxy-2′- fluorocytidine as a potent anti-hepatitis C virus (HCV) agent, a series of D- and L-2′-deoxy-2′-fluororibonucleosides with modifications at 5- and/or 4-positions were synthesized and evaluated for their in vitro activity against HCV and bovine viral diarrhea virus (BVDV). The key step in the synthesis, the introduction of 2′-fluoro group, was achieved by either fluorination of 2,2′-anhydronucleosides with hydrogen fluoride-pyridine or potassium fluoride, or a fluorination of arabinonucleosides with DAST. Among the 27 analogues synthesized, only the 5-fluoro compound, namely (2′R)-D-2′-deoxy-2′,5-difluorocytidine (13), demonstrated potent anti-HCV activity and toxicity to ribosomal RNA. The replacement of the 4-amino group with a thiol group resulted in the loss of activity, while the 4-methylthio substituted analogue (25) exhibited inhibition of ribosomal RNA. As N4-hydroxycytidine (NHC) had previously shown potent anti-HCV activity, we combined the two functionalities of the N4-hydroxyl and the 2′-fluoro into one molecule, resulting (2′R)-D-2′-deoxy- 2′-fluoro-N4-hydroxycytidine (23). However, this nucleoside showed neither anti-HCV activity nor toxicity. All the L-forms of the analogues were devoid of anti-HCV activity. None of the compounds showed anti-BVDV activity, suggesting that the BVDV system cannot always predict anti-HCV activity.