共查询到20条相似文献,搜索用时 15 毫秒
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David G. Twigg Dr. Noriyasu Kondo Sophie L. Mitchell Dr. Warren R. J. D. Galloway Dr. Hannah F. Sore Dr. Andrew Madin Prof. David R. Spring 《Angewandte Chemie (International ed. in English)》2016,55(40):12479-12483
Fragment‐based lead generation has proven to be an effective means of identifying high‐quality lead compounds for drug discovery programs. However, the fragment screening sets often used are principally comprised of sp2‐rich aromatic compounds, which limits the structural (and hence biological) diversity of the library. Herein, we describe strategies for the synthesis of a series of partially saturated bicyclic heteroaromatic scaffolds with enhanced sp3 character. Subsequent derivatization led to a fragment collection featuring regio‐ and stereo‐controlled introduction of substituents on the saturated ring system, often with formation of new stereocenters. 相似文献
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Gold‐Catalyzed Cyclization Leads to a Bridged Tetracyclic Indolenine that Represses β‐Lactam Resistance 下载免费PDF全文
Dr. Wenqing Xu Dr. Wei Wang Prof. Dr. Xiang Wang 《Angewandte Chemie (International ed. in English)》2015,54(33):9546-9549
A gold‐catalyzed desilylative cyclization was developed for facile synthesis of bridged tetracyclic indolenines, a common motif in many natural indole alkaloids. An antimicrobial screen of the cyclization products identified one compound which selectively potentiates β‐lactam antibiotics in methicillin‐resistant S. aureus (MRSA), and re‐sensitizes a variety of MRSA strains to β‐lactams. 相似文献
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Alexander A. Kirichok Dr. Iryna Shton Dr. Maria Kliachyna Dr. Iryna Pishel Dr. Pavel K. Mykhailiuk 《Angewandte Chemie (International ed. in English)》2017,56(30):8865-8869
The 2-substituted piperidine core is found in drugs (18 FDA-approved drugs), however, their spirocyclic analogues remain unknown. Described here is the synthesis of spirocyclic analogues for 2-substituted piperidines and a demonstration of their validation in drug discovery. 相似文献
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Overcoming the Unexpected Functional Inversion of a PqsR Antagonist in Pseudomonas aeruginosa: An In Vivo Potent Antivirulence Agent Targeting pqs Quorum Sensing 下载免费PDF全文
Cenbin Lu Christine K. Maurer Benjamin Kirsch Dr. Anke Steinbach Prof. Dr. Rolf W. Hartmann 《Angewandte Chemie (International ed. in English)》2014,53(4):1109-1112
The virulence regulator PqsR of Pseudomonas aeruginosa is considered as an attractive target for attenuating the bacterial pathogenicity without eliciting resistance. However, despite efforts and desires, no promising PqsR antagonist has been discovered thus far. Now, a surprising functionality change of a highly affine PqsR antagonist in P. aeruginosa is revealed, which is mediated by a bacterial signal molecule synthase and responsible for low cellular potency. Blockade of the susceptible position led to the discovery of the first antivirulence compound that is potent in vivo and targets PqsR, thus providing a proof of concept for this novel antivirulence therapy. 相似文献
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Cycloamidination of Aminoalkenes with Nitriles: Synthesis of Substituted 2‐Imidazolines and Tetrahydropyrimidines 下载免费PDF全文
Shujian Huang Yinlin Shao Prof. Dr. Lixin Zhang Prof. Dr. Xigeng Zhou 《Angewandte Chemie (International ed. in English)》2015,54(48):14452-14456
The first catalytic cycloamidination of aminoalkenes with nitriles has been achieved by using rare‐earth complexes. This reaction is equivalent to the desired intramolecular hydroamination of alkenylamidines, and allows a new direct access to substituted 2‐imidazolines and tetrahydropyrimidines in high yields under operationally simple reaction conditions. Moreover, the methodology is also efficient for synthesis of symmetric and unsymmetric bridged diimidazolines. Compared with the traditional stepwise‐mediated synthetic approaches, the present method avoids the use of additives and harsh reaction conditions, and thus leads to a completely different product distribution. Mechanistic data suggest that the reaction involves the initial NH activation by lanthanide complex followed by nitrile insertion into a Ln? N bond to form an amidinate lanthanide intermediate which undergoes the cyclization. 相似文献
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Activated 3-substituted isoindolinones have proved to be efficient nucleophiles in K2CO3-catalyzed Michael reactions of several types of electron-deficient olefins. Moreover, tricyclic pyrrolizidines have been conveniently synthesized via a modification of the described general protocol as a consequence of a cascade Michael/cyclization reaction of unsaturated aldehydes. 相似文献
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Furan‐Based o‐Quinodimethanes by Gold‐Catalyzed Dehydrogenative Heterocyclization of 2‐(1‐Alkynyl)‐2‐alken‐1‐ones: A Modular Entry to 2,3‐Furan‐Fused Carbocycles 下载免费PDF全文
Liejin Zhou Mingrui Zhang Dr. Wenbo Li Prof. Dr. Junliang Zhang 《Angewandte Chemie (International ed. in English)》2014,53(25):6542-6545
A strategy for in situ generation of furan‐based ortho‐quinodimethanes (o‐QDMs) by the gold(I)‐mediated dehydrogenative heterocyclization of 2‐(1‐alkynyl)‐2‐alken‐1‐ones in the presence of pyridine N‐oxide under mild reaction conditions was developed. These in situ furan‐based o‐QDMs were trapped by electron‐deficient olefins and alkynes, thus furnishing various 2,3‐furan‐fused carbocycles in good yields with high diastereo‐ and regioselectivities. 相似文献
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Zinc‐Catalyzed Alkyne Oxidation/CH Functionalization: Highly Site‐Selective Synthesis of Versatile Isoquinolones and β‐Carbolines 下载免费PDF全文
Long Li Bo Zhou Yong‐Heng Wang Chao Shu Yi‐Fei Pan Prof. Dr. Xin Lu Prof. Dr. Long‐Wu Ye 《Angewandte Chemie (International ed. in English)》2015,54(28):8245-8249
An efficient zinc(II)‐catalyzed alkyne oxidation/C? H functionalization sequence was developed, thus leading to highly site‐selective synthesis of a variety of isoquinolones and β‐carbolines. Importantly, in contrast to the well‐established gold‐catalyzed intermolecular alkyne oxidation, over‐oxidation can be completely suppressed in this system and the reaction most likely proceeds by a Friedel–Crafts‐type pathway. Mechanistic studies and theoretical calculations are described. 相似文献
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Sabrina Giofr Roberto Sala Egle Maria Beccalli Leonardo Lo Presti Gianluigi Broggini 《Helvetica chimica acta》2019,102(7)
A procedure for the iodoamination of unfunctionalized olefins tethered to a tosyl‐protected NH‐group has been developed. The combined use of KI and H2O2 in aqueous medium was effective for the preparation of iodomethyl‐substituted nitrogen‐containing heterocycles. The selective exo‐trig iodocyclization provided 1,2‐bifunctional 5‐, 6‐, and 7‐membered cyclic skeletons. 相似文献
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Often used as a common solvent for chemical reations and utilized widely in industry as a reagent, N,N-dimethylformamide (DMF) has played an important role in organic synthesis for a long time. Numerous highly useful articles and reviews discussing its utilizations have been published. With a focus on the performance of DMF as a multipurpose precursor for various units in numerous reactions, this Minireview summarizes recent developments in the employment of DMF in the fields of formylation, aminocarbonylation, amination, amidation, and cyanation, as well as its reaction with arynes. 相似文献
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Kathrin Bensberg Dr. Kevin A. Kunz Prof. Dr. Stefan F. Kirsch 《European journal of organic chemistry》2023,26(18):e202300212
In recent years, the development of synthetic methods to afford nitrogen-containing heterocycles has become increasingly popular. Among these, tetrazoles – an important class of aromatic heterocycles – are of significant interest for example, in medicinal chemistry serving as important bioisosteres. Herein, we present a method to easily access C-substituted tetrazoles via thermolysis of geminal diazido malonamides. Formation and functionalization of in situ formed isocyanates and corresponding reactions were also studied. 相似文献
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Van Baelen G Kuijer S Rýček L Sergeyev S Janssen E de Kanter FJ Maes BU Ruijter E Orru RV 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(52):15039-15044
Compared with the widespread use of carbonylative Pd-catalyzed cross-coupling reactions, similar reactions involving isocyanide insertion are almost virgin territory. We investigated the intramolecular imidoylative cross-coupling of N-(2-bromoaryl)amidines, leading to 4-aminoquinazolines. After thorough optimization of the reaction with respect to palladium source and loading, ligand, base, temperature, and solvent, a small library of 4-aminoquinazolines was prepared to determine the scope of this method. Various substituents are tolerated on the amidine and the isocyanide, providing efficient access to a broad range of diversely substituted 4-aminoquinazolines of significant pharmaceutical interest. 相似文献
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Yu N Wang C Zhao F Liu L Zhang WX Xi Z 《Chemistry (Weinheim an der Bergstrasse, Germany)》2008,14(18):5670-5679
Addition cyclization of 1,2,3,4-tetrasubstituted 1,4-dilithio-1,3-dienes (Type I) with four equivalents of various aromatic nitriles in the presence of hexamethylphosphoramide (HMPA) gives exclusively fully substituted pyridines in moderate to good yields. Similarly, trisubstituted pyridines can be prepared by the reaction of 2,3-dialkyl- or diaryl-substituted 1,4-dilithio-1,3-dienes (Type II) with nitriles. However, five- or six-membered-ring fused 2,3-disubstituted 1,4-dilithio-1,3-dienes (Type III) reacted with various aromatic and aliphatic nitriles without alpha-hydrogen atoms to afford tricyclic Delta1-bipyrrolines in high yields. The reaction of six-membered-ring fused 2,3-disubstituted 1,4-dilithio-1,3-diene (Type III) with 2-cyanopyridine afforded the corresponding pyridine, and no tricyclic Delta1-bipyrroline was observed. Seven-membered-ring fused dilithiodienes reacted with PhCN or trimethylacetonitrile to afford the corresponding pyridines in good yield. When 1,2,3,4-tetrasubstituted dilithio reagents (Type I) were treated with Me3SiCN, a tandem silylation/intramolecular substitution process readily occurred to yield siloles, whereas the reaction of 2,3-disubstituted dilithio reagents (Types II and III) with Me3SiCN gave rise to (Z,Z)-dienylsilanes with high stereoselectivity. These results revealed that the formation of tricyclic Delta1-bipyrrolines, pyridines, siloles, and (Z,Z)-dienylsilanes are strongly dependent on the substitution patterns of the dilithio butadienes and the nature of the nitriles employed. 相似文献