Metal- and Phenol-Free Synthesis of Biaryl Ethers: Access to Dibenzobistriazolo-1,4,7-oxadiazonines and Vancomycin-Like Glyco-Macrocycles as Antibacterial Agents

Abstract

An efficient synthesis of biaryl ethers, from electron-deficient aryl halides using NaH/DMSO under metal-and phenol-free conditions, has been achieved to access dibenzo-bistriazolo-1,4,7-oxadiazonines and vancomycin-like glycomacrocycles. A 44-membered glyco-macrocycle showed promising activity against vancomycin-resistant Staphylococcus aureus (VRSA).

Growing Impact of Intramolecular Click Chemistry in Organic Synthesis

“…Tripathi and co-workers used modular CuAAC mediated macrocyclization route and developed a Vancomycin-mimic glycomacrocycle of promising antibacterial activity (Scheme 29). [132] Sewald and co-workers made significant efforts to mimic the endocyclic trans-amide linkage of cryptophycin-52 (a macrocyclic antitumor agent) with 1,4-disubstituted 1H-1,2,3triazole ring. [133] The authors synthesized linear precursor 155 to study the macrocyclization of 'clicktophycin-52'(a cryptophycin-52 triazole analogue) through modular CuAAC click Scheme 25.…”

“…CuAAC mediated macrocyclization route for vancomycin-mimic glycomacrocycle 154. [132] Scheme 30. Synthesis of 'clicktophycin-52' 156 a triazole mimetic analogue of 'cryptophycin-52'.…”

“…Tripathi and co‐workers used modular CuAAC mediated macrocyclization route and developed a Vancomycin‐mimic glycomacrocycle of promising antibacterial activity (Scheme 29). [132] Thus, CuAAC Click conjugation of bis ‐azide 151 with sugar alkyne 25 in presence of CuSO 4 ⋅ 5H 2 O and sodium ascorbate in t ‐BuOH/H 2 O (v/v 1 : 1) afforded 152 in 98 % yield. For intramolecular click mediated cyclization, compound 152 was subject to selective to sequencial high‐yielding reactions including isopropylidene deprotection, NaIO 4 oxidation, NaBH 4 reduction and propargylation to get high yield of desired bis ‐alkyne 153 .…”

Synthesis of Bioactive 1,2,3-Triazole-Fused Macrocycles via Azide-Alkyne Cycloaddition

“…In 2018, Singh et al developed a vancomycin-like 44-membered biphenyl ether based macrocycles with triazole linkers 294a,b and evaluated their antibacterial activities (Schemes 34 and 35). 38 Their syntheses were undertaken by using the azidobiphenyls 293a and 293b along with the propargylated sugar moieties 292 and 296. The initial Cu-catalyzed AAC reaction conducted in between 293a and 292 in the CuI/DIPEA system in acetonitrile/water medium at 30 ℃ for 48 h afforded the target macrocycle 294a and its isomer 295 as an inseparable mixture with a combined yield 12% (Scheme 34).…”

Small Carbohydrate Derivatives as Potent Antibiofilm Agents

“…The emergence and spread of antibiotic-resistant pathogenic bacteria have posed a serious threat to human health. The situation is alarming, and there is an urgent need for the synthesis and development of new antimicrobials with novel mechanisms of action, which are not affected by the mechanisms existing in drug-resistant pathogens. − The formation of biofilms by most pathogenic bacteria is considered as one of the important mechanisms of antibiotic resistance and a key virulence factor for pathogens responsible for chronic infections . Biofilms are the communities of microorganisms attached to surfaces and play a significant role in the persistence of infections, resistance to environmental stress, and development of drug resistance toward antibiotics. , According to the National Institutes of Health (NIH), United States, about 65% of microbial diseases and more than 80% of all chronic infections are associated with biofilm formation .…”