101711-78-8Relevant articles and documents
Electrogenerated base-induced N-acylation of chiral oxazolidin-2-ones
Feroci,Inesi,Palombi,Rossi,Sotgiu
, p. 6185 - 6188 (2001)
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Substrate structure-activity relationships guide rational engineering of modular polyketide synthase ketoreductases
Bailey, Constance B.,Pasman, Marjolein E.,Keatinge-Clay, Adrian T.
, p. 792 - 795 (2016)
Modular polyketide synthase ketoreductases can set two chiral centers through a single reduction. To probe the basis of stereocontrol, a structure-activity relationship study was performed with three α-methyl, β-ketothioester substrates and four ketoreductases. Since interactions with the β-ketoacyl moiety were found to be most critical, residues implicated in contacting this moiety were mutated. Two mutations were sufficient to completely reverse the stereoselectivity of the model ketoreductase EryKR1, converting it from an enzyme that generates (2S,3R)-products into one that yields (2S,3S)-products.
Liquid Chromatographic Resolution of Racemic 2-Oxazolidinones and their Analogs on Seven Pirkle-Type Chiral Stationary Phases
Yu, Jeong Jae,Hyun, Myung Ho,Armstrong, Daniel W.,Breitbach, Zachary S.,Ryoo, Jae Jeong
, p. 723 - 726 (2015)
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Modular Synthesis of Diverse Natural Product-Like Macrocycles: Discovery of Hits with Antimycobacterial Activity
Dow, Mark,Marchetti, Francesco,Abrahams, Katherine A.,Vaz, Luis,Besra, Gurdyal S.,Warriner, Stuart,Nelson, Adam
, p. 7207 - 7211 (2017)
A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12–20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity.
Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
, p. 1080 - 1090 (2020)
Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
Stapled Peptides with γ-Methylated Hydrocarbon Chains for the Estrogen Receptor/Coactivator Interaction
Speltz, Thomas E.,Fanning, Sean W.,Mayne, Christopher G.,Fowler, Colin,Tajkhorshid, Emad,Greene, Geoffrey L.,Moore, Terry W.
, p. 4252 - 4255 (2016)
"Stapled" peptides are typically designed to replace two non-interacting residues with a constraining, olefinic staple. To mimic interacting leucine and isoleucine residues, we have created new amino acids that incorporate a methyl group in the γ-position of the stapling amino acid S5. We have incorporated them into a sequence derived from steroid receptor coactivator2, which interacts with estrogen receptorα. The best peptide (IC50=89nm) replaces isoleucine689 with an S-γ-methyl stapled amino acid, and has significantly higher affinity than unsubstituted peptides (390 and 760nm). Through X-ray crystallography and molecular dynamics studies, we show that the conformation taken up by the S-γ-methyl peptide minimizes the syn-pentane interactions between the α- and γ-methyl groups.
Thermal proteome profiling efficiently identifies ribosome destabilizing oxazolidinones
N?cker, Christina,Kaiser, Nadine,Foley, Daniel,Sievers, Sonja,Janning, Petra,Waldmann, Herbert,Laraia, Luca
supporting information, (2021/04/22)
Identifying the targets of bioactive small molecules is a challenging endeavor for which no general solution currently exists. Classical affinity purification experiments suffer from the need to functionalise a bioactive compound and link it to a solid support, which may interfere with target binding. A modern mass spectrometry-based proteomics technique that has partially circumvented this problem is thermal proteome profiling (TPP), which determines the effect of an unmodified small molecule on the thermal stability of the whole proteome simultaneously. Here, we use TPP to identify the mode-of-action of a newly-discovered autophagy inhibitor based on oxazolidinones often employed as chiral auxiliaries. Surprisingly, a significant portion of all ribosomal proteins were found to be destabilized by the inhibitor, highlighting the utility of this technology for determining a challenging mode-of-action.
Synthesis and Bioactivity of a Macrocidin B Stereoisomer
Weber, Stefanie E.,Ga?, Juliane,Zeng, Haoxuan,Erb-Brinkmann, Maike,Schobert, Rainer
supporting information, p. 8273 - 8276 (2021/10/25)
A stereoisomer of macrocidin B, a presumed metabolite of the fungus Phoma macrostoma, was synthesized in 18 steps and 2.7% yield from protected l-tyrosine that was N-β-ketoacylated with a fully functionalized octanoyl Meldrum's acid. Dieckmann condensation gave a 3-acyltetramic acid, which was macrocyclized via Williamson etherification between the phenol and epi-bromohydrin termini. This macrocidin B stereoisomer showed a weaker herbicidal effect than macrocidin A and no similar inhibitory effect on biofilms of Staphylococcus aureus.
