Stereoselective synthesis of sugar-based β-lactam derivatives: docking studies and its biological evaluation

• Published in: Tetrahedron Vol. 68; no. 14; pp. 3037 - 3045
• Main Authors: Nagarajan, Subbiah, Arjun, Pandian, Raaman, Nanjian, Shah, Anup, Sobhia, M. Elizabeth, Das, Thangamuthu Mohan
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 08.04.2012; Elsevier
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimicrobial studies; Biological and medical sciences; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Organic; Cycloaddition; Derivatives; Docking; Docking analysis; Exact sciences and technology; General aspects; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Hydroxyl groups; Ketenes; Medical sciences; Organic chemistry; Pharmacology. Drug treatments; Physical Sciences; Preparations and properties; Science & Technology; Staudinger reaction; Stereoselectivity; Sugar-β-lactam; Surgical implants; Synthesis (chemistry); Tetracyclines; RVZOMZBEHBKUNX-DGCCNBPESA-N; MSOHVCOABLXXCO-QAIULHONSA-N; Sugar-β-lactam; DHMILLDJQQNUGN-FUBPBSFISA-N; Stereoselectivity; IQNCNYAVUFNAFC-XLLZEUPCSA-N; WACAIJVCSJQYPY-XLLZEUPCSA-N; Staudinger reaction; BHIUTBTVYZWKCS-OVJKROGOSA-N; Docking analysis; ZNVTUILTTXHIHY-XLLZEUPCSA-N; OAIGDABAPMQZFQ-MIJANOMNSA-N; Antimicrobial studies; BBSOCPUJBXLUBF-CYNAVLNLSA-N; IXXGXBZMVRJZMJ-BIHVHAKJSA-N; ASYMMETRIC-SYNTHESIS; CRYSTAL-STRUCTURE; BUILDING-BLOCKS; 2+2 CYCLOADDITION; ACETALS; Sugar-beta-lactam; 4,6-O-BUTYLIDENE-ALPHA-D-GLUCOPYRANOSE; D-GLUCOSE; Nitrogen heterocycle; Lactam; Molecular interaction; Antimicrobial agent; Ketenes; Molecular model; Hydroxyl group; Chemical synthesis; Tetracycline derivatives; Exo stereoisomer; β-Lactams; Oside; Imine; Ketone; Biological activity; Diastereoselectivity; Tetracycline; In vivo; Antibiotic; Cycloaddition; Azetidine derivatives; Affinity; Hydrogen bond
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.02.017

Highly diastereoselective synthesis of cis-β-lactams via [2+2] cycloaddition reactions of sugar-imine derivative possessing free hydroxyl groups at C-2 and C-3 positions and ketenes is described. exo-Approach of sugar-imine with ketene leads to the stereoselective formation of cis product and it is facilitated by hydrogen bonding interaction of C2–OH with carbonyl group of ketene. Docking studies show that these derivatives are having greater affinity towards PBP and it has been validated by in vivo studies. Among the different sugar-based azetidine-2-ones, compounds 6a and 6d were superior in activity to the commercial antibiotic tetracycline. [Display omitted]