25756-29-0Relevant articles and documents
Direct Copper-Catalyzed Three-Component Synthesis of Sulfonamides
Chen, Yiding,Murray, Philip R. D.,Davies, Alyn T.,Willis, Michael C.
supporting information, p. 8781 - 8787 (2018/07/29)
First introduced into medicines in the 1930s, the sulfonamide functional group continues to be present in a wide range of contemporary pharmaceuticals and agrochemicals. Despite their popularity in the design of modern bioactive molecules, the underpinning methods for sulfonamide synthesis are essentially unchanged since their introduction, and rely on the use of starting materials with preinstalled sulfur-functionality. Herein we report a direct single-step synthesis of sulfonamides that combines two of the largest monomer sets available in discovery chemistry, (hetero)aryl boronic acids and amines, along with sulfur dioxide, using a Cu(II) catalyst, to deliver a broad range of sulfonamides. Sulfur dioxide is provided by the surrogate reagent DABSO. The reaction tolerates broad variation in both coupling partners, including aryl, heteroaryl and alkenyl boronic acids, as well as cyclic and acyclic alkyl secondary amines, and primary anilines. We validate the method by showing that a variety of drugs, and drug-fragments, can be incorporated into the process.
Conformational Aspects in the Design of Inhibitors for Serine Hydroxymethyltransferase (SHMT): Biphenyl, Aryl Sulfonamide, and Aryl Sulfone Motifs
Schwertz, Geoffrey,Frei, Michelle S.,Witschel, Matthias C.,Rottmann, Matthias,Leartsakulpanich, Ubolsree,Chitnumsub, Penchit,Jaruwat, Aritsara,Ittarat, Wanwipa,Sch?fer, Anja,Aponte, Raphael A.,Trapp, Nils,Mark, Kerstin,Chaiyen, Pimchai,Diederich, Fran?ois
supporting information, p. 14345 - 14357 (2017/10/09)
Malaria remains a major threat to mankind due to the perpetual emergence of resistance against marketed drugs. Twenty-one pyrazolopyran-based inhibitors bearing terminal biphenyl, aryl sulfonamide, or aryl sulfone motifs were synthesized and tested towards serine hydroxymethyltransferase (SHMT), a key enzyme of the folate cycle. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target, as well as PfNF54 strains in cell-based assays in the low nanomolar range (18–56 nm). Seven co-crystal structures with P. vivax (Pv) SHMT were solved at 2.2–2.6 ? resolution. We observed an unprecedented influence of the torsion angle of ortho-substituted biphenyl moieties on cell-based efficacy. The peculiar lipophilic character of the sulfonyl moiety was highlighted in the complexes with aryl sulfonamide analogues, which bind in their preferred staggered orientation. The results are discussed within the context of conformational preferences in the ligands.
Heterogeneous CeO2 catalyst for the one-pot synthesis of organic carbamates from amines, CO2 and alcohols
Honda, Masayoshi,Sonehara, Satoru,Yasuda, Hiroshi,Nakagawa, Yoshinao,Tomishige, Keiichi
scheme or table, p. 3406 - 3413 (2012/01/15)
Heterogeneous CeO2 catalyst can catalyze the one-pot synthesis of methyl benzylcarbamate from benzylamine, CO2 and methanol. The yield of methyl benzylcarbamate reached 92% at >99% benzylamine conversion and 92% benzylamine-based selectivity even in the absence of the dehydrating agents. The catalyst is reusable after the calcination at 873 K for 3 h. Various carbamates can be synthesized with good yield and high selectivity by the reaction of amines + CO2 + alcohols over CeO2. The main formation route of methyl benzylcarbamate is suggested to be the reaction of dimethyl carbonate or the precursor of dimethyl carbonate formation with benzylamine.