160332-70-7Relevant articles and documents
Synthesis and biological evaluation of triazolyl-substituted benzyloxyacetohydroxamic acids as LpxC inhibitors
Hoff, Katharina,Mielniczuk, Sebastian,Agoglitta, Oriana,Iorio, Maria Teresa,Caldara, Manlio,Bülbül, Emre F.,Melesina, Jelena,Sippl, Wolfgang,Holl, Ralph
, (2020)
The bacterial deacetylase LpxC is a promising target for the development of antibiotics selectively combating Gram-negative bacteria. To improve the biological activity of the reported benzyloxyacetohydroxamic acid 9 ((S)-N-hydroxy-2-{2-hydroxy-1-[4-(phenylethynyl)phenyl]ethoxy}acetamide), its hydroxy group was replaced by a triazole ring. Therefore, in divergent syntheses, triazole derivatives exhibiting rigid and flexible lipophilic side chains, different configurations at their stereocenter, and various substitution patterns at the triazole ring were synthesized, tested for antibacterial and LpxC inhibitory activity, and structure-activity relationships were deduced based on docking and binding energy calculations.
Reprogramming Epoxide Hydrolase to Improve Enantioconvergence in Hydrolysis of Styrene Oxide Scaffolds
Li, Fu-Long,Qiu, Yan-Yan,Zheng, Yu-Cong,Chen, Fei-Fei,Kong, Xu–Dong,Xu, Jian-He,Yu, Hui-Lei
, p. 4699 - 4706 (2020/09/21)
Enantioconvergent hydrolysis by epoxide hydrolase is a promising method for the synthesis of important vicinal diols. However, the poor regioselectivity of the naturally occurring enzymes results in low enantioconvergence in the enzymatic hydrolysis of styrene oxides. Herein, modulated residue No. 263 was redesigned based on structural information and a smart variant library was constructed by site-directed modification using an “optimized amino acid alphabet” to improve the regioselectivity of epoxide hydrolase from Vigna radiata (VrEH2). The regioselectivity coefficient (r) of variant M263Q for the R-isomer of meta-substituted styrene oxides was improved 40–63-fold, and variant M263V also exhibited higher regioselectivity towards the R-isomer of para-substituted styrene oxides compared with the wild type, which resulted in improved enantioconvergence in hydrolysis of styrene oxide scaffolds. Structural insight showed the crucial role of residue No. 263 in modulating the substrate binding conformation by altering the binding surroundings. Furthermore, increased differences in the attacking distance between nucleophilic residue Asp101 and the two carbon atoms of the epoxide ring provided evidence for improved regioselectivity. Several high-value vicinal diols were readily synthesized (>88% yield, 90%–98% ee) by enantioconvergent hydrolysis using the reprogrammed variants. These findings provide a successful strategy for enhancing the enantioconvergence of native epoxide hydrolases through key single-site mutation and more powerful enzyme tools for the enantioconvergent hydrolysis of styrene oxide scaffolds into single (R)-enantiomers of chiral vicinal diols. (Figure presented.).
Kinetic Resolution of 1,2-Diols via NHC-Catalyzed Site-Selective Esterification
Liu, Bin,Yan, Jiekuan,Huang, Ruoyan,Wang, Weihong,Jin, Zhichao,Zanoni, Giuseppe,Zheng, Pengcheng,Yang, Song,Chi, Yonggui Robin
supporting information, p. 3447 - 3450 (2018/06/26)
A kinetic resolution of 1,2-diols bearing both a secondary and a primary alcohol motif through an N-heterocyclic carbene-catalyzed oxidative acylation reaction has been developed. A site- and enantioselective esterification reaction is involved for this process. Both the monoacylated diols obtained and the remaining enantioenriched 1,2-diols are versatile building blocks for the preparation of functional molecules with proven biological activities.