56733-83-6Relevant academic research and scientific papers
Sugar-Pirating as an Enabling Platform for the Synthesis of 4,6-Dideoxyhexoses
Zhang, Yinan,Zhang, Jianjun,Ponomareva, Larissa V.,Cui, Zheng,Van Lanen, Steven G.,Thorson, Jon S.,Thorson, Jon S.
supporting information, p. 9389 - 9395 (2020/06/27)
An efficient divergent synthetic strategy that leverages the natural product spectinomycin to access uniquely functionalized monosaccharides is described. Stereoselective 2′- and 3′-reduction of key spectinomycin-derived intermediates enabled facile acces
METHODS AND COMPOSITIONS FOR PRODRUG FORMS OF SPECTINOMYCIN AND SPECTINAMIDE ANALOGS
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Paragraph 0583-0584; 0595, (2020/06/01)
In one aspect, the disclosure relates to substituted spectinomycin analogs, including substituted aminomethyl spectinomycin analogs and substituted spectinamide analogs, with increased tolerability and safety, including improved tolerability to parenteral
Spectinomycin derivative, preparation method thereof and application of derivative
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Paragraph 0044; 0057; 0058; 0059; 0070, (2018/07/15)
The invention discloses a spectinomycin derivative, a preparation method thereof and an application of the derivative, and aims to solve the problems of poor mycobacterium-tuberculosis-resistant effect of spectinomycin molecules and the like in prior art, improve target ability of tuberculosis cells, enhance solubility of drugs and relieve toxicity of the drugs for normal cells. According to the spectinomycin derivative, natural amino acid has good biocompatibility and affinity, serves as a carrier and is introduced into the spectinomycin molecules to form a novel spectinomycin derivative by apreparation method of amino protection, carbonyl reduction, amidation and deprotection of spectinomycin. Experimental results show that the antibacterial activity of the spectinomycin derivative formycobacterium tuberculosis is improved, and anti-tuberculous time is prolonged. The spectinomycin derivative has excellent mycobacterium-tuberculosis-resistant activity, so that the spectinomycin derivative has a good application prospect in anti-tuberculous drugs.
Structure-activity relationships of spectinamide antituberculosis agents: A dissection of ribosomal inhibition and native efflux avoidance contributions
Liu, Jiuyu,Bruhn, David F.,Lee, Robin B.,Zheng, Zhong,Janusic, Tanja,Scherbakov, Dimitri,Scherman, Michael S.,Boshoff, Helena I.,Das, Sourav,Rakesh,Waidyarachchi, Samanthi L.,Brewer, Tiffany A.,Gracia, Bego?a,Yang, Lei,Bollinger, John,Robertson, Gregory T.,Meibohm, Bernd,Lenaerts, Anne J.,Ainsa, Jose,B?ttger, Erik C.,Lee, Richard E.
, p. 72 - 88 (2017/12/06)
Spectinamides are a novel class of antitubercular agents with the potential to treat drug-resistant tuberculosis infections. Their antitubercular activity is derived from both ribosomal affinity and their ability to overcome intrinsic efflux mediated by the Mycobacterium tuberculosis Rv1258c efflux pump. This study explores the structure-activity relationships through analysis of 50 targeted spectinamides. Compounds are evaluated for ribosomal translational inhibition, MIC activity in Rv1258c efflux pump deficient and wild type tuberculosis strains, and efficacy in an acute model of tuberculosis infection. The results of this study show a narrow structure-activity relationship, consistent with a tight ribosome-binding pocket and strict structural requirements to overcome native efflux. Rationalization of ribosomal inhibition data using molecular dynamics simulations showed stable complex formation for halogenated spectinamides consistent with the long post antibiotic effects observed. The lead spectinamides identified in this study demonstrated potent MIC activity against MDR and XDR tuberculosis and had desirable antitubercular class specific features including low protein binding, low microsomal metabolism, no cytotoxicity, and significant reductions in bacterial burdens in the lungs of mice infected with M. tuberculosis. The structure-activity relationships detailed here emphasize the need to examine efflux-mediated resistance in the design of antituberculosis drugs and demonstrate that it is possible to overcome intrinsic efflux with synthetic modification. The ability to understand the structure requirements for this class has produced a variety of new substituted spectinamides, which may provide useful alternative candidates and promote the further development of this class.
A concise, stereocontrolled synthesis of spectinomycin
Cuny, Eckehard,Lichtenthaler, Frieder W.
, p. 1120 - 1124 (2007/10/03)
A simple and concise synthesis of the antibiotic spectinomycin is described. The key step comprises a reaction cascade initiated by the β-selective 5-O-glycosylation of an N,N-blocked myo-1,3-inosadiamine 10 with a suitable actinospectosyl donor-the d-glu
A concise and general method for doubly attaching 2-ketosugars to aglycon diols: Synthesis of the gomphosides and spectinomycin
Lichtenthaler, Frieder W.,Cuny, Eckehard,Sakanaka, Osamu
, p. 4944 - 4948 (2007/10/03)
(Chemical Equation Presented) Spectinomycin and the gomphosides: Use of 6-deoxyhexulosyl derivatives of D-glucose in Ag2CO 3-mediated glycosylation of gomphogenin and actinamine has allowed the first syntheses of cardiac glycosides with ring A-annulated sugar components (see picture; Bz = benzoyl) and an alternate synthesis of the antibiotic spectinomycin.
Oxidation and Alkylation of Spectinomycin Derivatives: Synthesis of Trospectomycin from Spectinomycin
Herrinton, Paul M.,Klotz, Karen L.,Hartley, William M.
, p. 678 - 682 (2007/10/02)
Trospectomycin can be prepared in five steps from spectinomycin.The overall yield of the process is 13.3 percent.The synthesis involves a new oxidation of silyl enol ether 4 to enone 5 by use of an alkyl hydroperoxide.This reaction is mild and very selcti
