Synthesis of Adenine Nucleosides with a Reactive (β-Iodovinyl)sulfone or (β-Keto)sulfone Group at the C2 Position and Their Polymerase-Catalyzed Incorporation into DNA

Molecules, Journal Year: 2025, Volume and Issue: 30(6), P. 1358 - 1358

Published: March 18, 2025

Iodosulfonylation of an ethynyl group at the C2 position 2′-deoxyadenosine or adenosine with TsI provides (E)-2-(β-iodovinyl)sulfones. The latter undergo nucleophilic substitution amines via addition–elimination to give β-sulfonylvinylamines (enamines). Acid-catalyzed hydrolysis 2-(β-keto)sulfones, mechanistically different probes that react alkyl halides, resulting in α-alkylation. Adenine nucleosides a β-ketosulfone C2, during conversion their 5′-triphosphate form, unexpected 2-carboxylic acid nucleotides. 2′-deoxyadenosine-2-carboxylic was incorporated by human DNA polymerase into one-nucleotide gap substrate.

Language: Английский

Mechanistic Exploration of N-Heterocyclic Carbene Boranes as the Hydrogen Atom Transfer Reagent in Selective Hydrodefluorination Reactions

ACS Catalysis, Journal Year: 2024, Volume and Issue: unknown, P. 17547 - 17555

Published: Nov. 13, 2024

In the modern era of organic synthesis, mechanisms centered on radical intermediates have become increasingly impactful. Among all these, hydrogen atom transfer (HAT) represents one most fundamental chemical reaction steps and has found applications in designing practical transformations. Herein, we present a detailed case study selective hydrodefluorination trifluoromethylarenes utilizing N-heterocyclic carbene boranes (NHC-boranes) as donor. Under optimal conditions featuring an acridine-based photocatalyst, complete selectivity for mono-hydrodefluorination was achieved across wide array substrates. Comprehensive mechanistic studies combining experimental computational approaches disproved chain process involving fluorine but rather pointed to HAT non-chain mechanism, where key step involves difluorobenzylic abstracting from NHC-borane generate boryl polarity-matched fashion. Evaluation selection Lewis base-ligated revealed molecular descriptors critical outcomes this reaction, classification model built explain structure–reactivity relationship how various elementary can be influenced. These results collectively provide valuable information future design increase utility chemistry.

Language: Английский

Late-Stage Functionalization of Guanine-Based Nucleosides, Nucleotides, and Oligonucleotide: Synthesis and Derivatization of Tricyclic Nucleoside Analogues

Organic Letters, Journal Year: 2024, Volume and Issue: 26(50), P. 10891 - 10896

Published: Dec. 10, 2024

We report here the synthesis of tricyclic nucleoside analogues via acid-catalyzed cyclization guanine with 1,1,3,3-tetramethoxypropane. The method enables use hydroxyl-unprotected antiviral drugs (acyclovir, ganciclovir, and penciclovir), guanosines, oligonucleotide, triazole-linked dimers as substrates. Nucleoside trimer tetramer were synthesized by derivatization reactions.

Language: Английский