2407-11-6Relevant academic research and scientific papers
Stereodivergent, Diels-Alder-initiated organocascades employing α,β-unsaturated acylammonium salts: scope, mechanism, and application
Abbasov, Mikail E.,Hudson, Brandi M.,Tantillo, Dean J.,Romo, Daniel
, p. 1511 - 1524 (2017)
Chiral α,β-unsaturated acylammonium salts are novel dienophiles enabling enantioselective Diels-Alder-lactonization (DAL) organocascades leading to cis- and trans-fused, bicyclic γ- and δ-lactones from readily prepared dienes, commodity acid chlorides, and a chiral isothiourea organocatalyst under mild conditions. We describe extensions of stereodivergent DAL organocascades to other racemic dienes bearing pendant secondary and tertiary alcohols, and application to a formal synthesis of (+)-dihydrocompactin is described. A combined experimental and computational investigation of unsaturated acylammonium salt formation and the entire DAL organocascade pathway provide a rationalization of the effect of Br?nsted base additives and enabled a controllable, diastereodivergent DAL process leading to a full complement of possible stereoisomeric products. Evaluation of free energy and enthalpy barriers in conjunction with experimentally observed temperature effects revealed that the DAL is a rare case of an entropy-controlled diastereoselective process. NMR analysis of diene alcohol-Br?nsted base interactions and computational studies provide a plausible explanation of observed stabilization of exo transition-state structures through hydrogen-bonding effects.
Characterization of the reactivity of luciferin boronate - A probe for inflammatory oxidants with improved stability
?wierczyńska, Ma?gorzata,Grzelakowska, Aleksandra,Modrzejewska, Julia,Podsiad?y, Rados?aw,S?owiński, Daniel,Siarkiewicz, Przemys?aw,Szala, Marcin,Zielonka, Jacek
, (2020/08/12)
Boronate derivatives of luciferin, containing oxidant-activated self-immolative moieties, recently have been developed for bioluminescent detection of hydrogen peroxide in animal models. Here, we report the synthesis and characterization of luciferin boronic acid pinacol ester (LBE) as a probe for detection of hydrogen peroxide, hypochlorous acid, and peroxynitrite, with improved stability and response time. HPLC analyses showed that LBE quickly hydrolyzes in phosphate buffer to luciferin boronic acid (LBA). Hydrogen peroxide oxidizes LBA slowly, with the formation of luciferase substrate, luciferin (Luc-OH), as the only product. Hypochlorite also oxidizes LBA to luciferin, but the subsequent reaction of Luc-OH with hypochlorite gives a chlorinated luciferin Luc–OH–Cl, which has a higher fluorescence quantum yield than luciferin at pH 7.4 and is also a substrate for luciferase (Takakura H, et. all. ChemBioChem 2012; 13:1424). Similar to other boronate probes, LBA is oxidized by peroxynitrite in two pathways. Luc-OH is the product of the major pathway, common for all the oxidants tested, whereas the non-fluorescent nitrated derivative, Luc-NO2, is formed in the minor pathway, specific for peroxynitrite. Formation of luciferin radical intermediate in the minor pathway has been confirmed by EPR spin trapping and mass spectrometric analyses of the spin adducts. We conclude that LBE shows potential as an improved probe for the detection of inflammatory oxidants in biological settings. Complementation of the bioluminescence measurements by HPLC or LC-MS-based identification of chlorinated and nitrated luciferin(s) will help identify the oxidants detected.
Synthesis of N-Peptide-6-Amino-d-Luciferin Conjugates with Optimized Fragment Condensation Strategy
Kovács, Anita K.,Hegyes, Péter,Szebeni, Gábor J.,Bogár, Krisztián,Puskás, László G.,Tóth, Gábor K.
, p. 1209 - 1215 (2018/09/27)
Abstract: The synthesis of peptide-luciferin conjugates has a pivotal role in the development of bioluminescent detection systems that are based on the determination of protease enzyme activity. This work describes the optimized synthesis of an N-peptide-6-amino-d-luciferin conjugate (Fmoc-Gly-Pro-6-amino-d-luciferin) with a simple fragment condensation method in adequate yields. Fmoc-Gly-Pro-6-amino-d-luciferin was produced from a previously synthesized Fmoc-Gly-Pro-OH and also previously synthesized 6-amino-2-cyanobenzothiazole with an optimized method, to which conjugate cysteine was added in an also improved way. The resulting conjugate was successfully used in a bioluminescent system, in vitro, demonstrating the applicability of the method. Graphical Abstract: [Figure not available: see fulltext.].
Small-compound enhancers for functional O-mannosylation of alpha-dystroglycan, and uses thereof
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Page/Page column 23, (2019/03/14)
The present invention provides compounds that can enhance functional O-mannosylation of proteins including alpha-dystroglycan. Also provided are methods of preparation of the compounds defined by the formula I. Also provided are the methods of using the compounds or the pharmaceutical acceptable salts or prodrugs thereof in treating and preventing subjects suffering from the diseases including muscular dystrophies and cancers.
General Entry into o-,o′-Heteroatom-Linked N-(Hetero)aryl-Imidazole Motifs by Gold-Catalysed Formal [3+2]-Dipolar Cycloaddition
Garzón, Miguel,Arce, Elsa M.,Reddy, Raju Jannapu,Davies, Paul W.
supporting information, p. 1837 - 1843 (2017/06/09)
A general redox-neutral approach into the o-,o′-heteroatom-linked N-(hetero)aryl-imidazole family of heteroaromatics has been developed. New types of heteroatom substituted carbimidoyl nitrenoids are efficiently realised from robust, bench-stable N-(heteroaryl)-pyridinium-N-aminides by formal gold-catalysed [3+2]-dipolar cycloadditions across ynamides. Broad structural variety and functional group tolerance allows rapid access into diverse functionalised scaffolds, as exemplified by the preparation of 8 different heteroaromatic cores. (Figure presented.).
Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole
Hauser, Jacob R.,Beard, Hester A.,Bayana, Mary E.,Jolley, Katherine E.,Warriner, Stuart L.,Bon, Robin S.
, p. 2019 - 2025 (2016/10/05)
2-Cyanobenzothiazoles (CBTs) are useful building blocks for: 1) luciferin derivatives for bioluminescent imaging; and 2) handles for bioorthogonal ligations. A particularly versatile CBT is 6-amino-2-cyanobenzothiazole (ACBT), which has an amine handle for straight-forward derivatisation. Here we present an economical and scalable synthesis of ACBT based on a cyanation catalysed by 1,4-diazabicyclo[2.2.2]octane (DABCO), and discuss its advantages for scale-up over previously reported routes.
Small molecules enhance functional O-mannosylation of Alpha-dystroglycan
Lv, Fengping,Li, Zhi-Fang,Hu, Wenhao,Wu, Xiaohua
supporting information, p. 7661 - 7670 (2015/12/18)
Alpha-dystroglycan (α-DG), a highly glycosylated receptor for extracellular matrix proteins, plays a critical role in many biological processes. Hypoglycosylation of α-DG results in various types of muscular dystrophies and is also highly associated with progression of majority of cancers. Currently, there are no effective treatments for those devastating diseases. Enhancing functional O-mannosyl glycans (FOG) of α-DG on the cell surfaces is a potential approach to address this unmet challenge. Based on the hypothesis that the cells can up-regulate FOG of α-DG in response to certain chemical stimuli, we developed a cell-based high-throughput screening (HTS) platform for searching chemical enhancers of FOG of α-DG from a large chemical library with 364,168 compounds. Sequential validation of the hits from a primary screening campaign and chemical works led to identification of a cluster of compounds that positively modulate FOG of α-DG on various cell surfaces including patient-derived myoblasts. These compounds enhance FOG of α-DG by almost ten folds, which provide us powerful tools for O-mannosylation studies and potential starting points for the development of drug to treat dystroglycanopathy.
Site-specific immobilization of biomolecules by a biocompatible reaction between terminal cysteine and 2-cyanobenzothiazole
Wang, Ping,Zhang, Chong-Jing,Chen, Ganchao,Na, Zhenkun,Yao, Shao Q.,Sun, Hongyan
supporting information, p. 8644 - 8646 (2013/09/23)
We report herein a new site-specific microarray immobilization method based on a biocompatible reaction between terminal cysteine and 2-cyanobenzothiazole (CBT). This immobilization strategy has been successfully applied to anchor small molecules, peptides and proteins onto microarrays.
Synthesis and inhibition effects on 5-HT6 receptor of benzothiazole derivatives
Hayat, Faisal,Yoo, Euna,Rhim, Hyewhon,Choo, Hea-Young Park
, p. 495 - 499 (2013/08/25)
A novel series of aryl sulfonylpiperazine derivatives (5-15) were synthesized as 5-HT6 ligands. In vitro assay was evaluated by measuring the 5-HT-induced Ca2+ increases using HeLa cell line expressing the cloned human 5-HT6 receptor, and the compound 13 showed potent 5-HT6 receptor antagonistic effect with IC50 value of 3.9 μM. Compound 13 also showed good selectivity on the 5-HT6 over 5-HT4 and 5-HT7 receptors.
Triazolbenzo[d]thiazoles: Efficient synthesis and biological evaluation as neuroprotective agents
Avila, Belem,Roth, Aaron,Streets, Heather,Kurth, Mark J.,Dwyer, Donard S.
, p. 5976 - 5978,3 (2020/08/31)
A number of (1H-1,2,3-triazol-1-yl)benzo[d]thiazoles were synthesized utilizing a versatile Cu-catalyzed azide-alkyne click reaction (CuAAC) on tautomeric benzo[4,5]thiazolo[3,2-d]tetrazole (1) and 2-azidobenzo[d]thiazole (2) starting materials. Moreover, one of the resulting products of this investigation, triazolbenzo[d]thiazole 22, was found to possess significant neuroprotective activity in human neuroblastoma (SH-SY5Y) cells.
