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New carbonyl sulfoxonium ylide glyco-reagents have been developed, enabling the synthesis of versatile heteroarene C-glycosides through a Ru-catalyzed C-H activation/annulation strategy. These reactions tolerate various saccharide donors and represent a significant advance in the stereoselective synthesis of heterocyclic C-glycosides. Furthermore, the strategy and methods could be applied to large-scale reactions and late-stage modifications of some structurally complex natural products or drugs.
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http://dx.doi.org/10.1021/acs.orglett.4c01287 | DOI Listing |
Sci Adv
September 2025
Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health and
Ketonyl -glycosides, a vital subclass of alkyl -glycosides, play essential roles in drug discovery, biochemistry, and materials sciences. However, a practical strategy that merges bench-stable glycosyl donors with styrenes-a ubiquitous class of synthetic building blocks-remains elusive. Herein, we report a simple and general approach for synthesizing ketonyl -glycosides.
View Article and Find Full Text PDFAcc Chem Res
August 2025
The Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, People's Republic of China.
ConspectusOxygen-containing heterocycles are increasingly recognized for their biological significance, especially in the field of drug discovery. Therefore, the enantioselective synthesis of oxygen-containing heterocycles has attracted great attention in the past few decades, and many ingenious synthetic strategies have been developed. Despite remarkable progress, they are often limited in terms of the diversity of target scaffolds, accessibility of starting materials, substrate scope, and stereoselectivity.
View Article and Find Full Text PDFJ Am Chem Soc
April 2025
Department of Chemistry and Biochemistry, University of Oklahoma, 101 Stephenson Parkway, Norman, Oklahoma 73019-5251, United States.
Late-stage functionalization (LSF) is a crucial strategy in drug discovery, allowing the modification of complex molecules, including pharmaceuticals, to enhance chemical diversity in drug libraries. We harness the chemoselectivity of sulfenylcarbenes, which selectively react with alkenes even in the presence of more reactive functional groups such as alcohols, carboxylic acids, and amines. This reactivity allows sulfenylcarbenes to insert a single carbon atom bearing diverse functional groups, transforming pyrroles, indoles, and imidazoles into synthetically challenging pyridines, quinolines, and pyrimidines, respectively.
View Article and Find Full Text PDFJ Org Chem
April 2025
Department of Discovery Chemistry, Merck & Co., Inc., 33 Ave. Louis Pasteur, Boston, Massachusetts 02215, United States.
Carbohydrates constitute an important class of biologically relevant natural products. Among the synthetic glycomimetics, glycosides are particularly interesting due to their chemical and metabolic stability toward acidic and enzymatic hydrolysis at the anomeric position. The stereochemical outcomes of traditional methodologies to access glycosides rely heavily on substrate control.
View Article and Find Full Text PDFChem Commun (Camb)
April 2025
The Zhongzhou Laboratory for Integrative Biology, School of Pharmacy, Henan University, Kaifeng, Henan 475004, China.
A novel strategy for the synthesis of 2-glycosyl-quinazolines and 5-glycosyl-pyrazolo[1,2-]cinnolines has been established through an Ir-catalyzed C-H activation/annulation process. This approach features mild reaction conditions, exhibits good tolerance to diverse functional groups, and facilitates the stereoselective construction of heterocyclic -glycosides. Significantly, this method is amenable to the late-stage modification of structurally intricate natural products, thus holding great potential in the field of organic synthesis and pharmaceutical chemistry.
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