- CHEMOSELECTIVE ENRICHMENT FOR COMPOUND ISOLATION
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Chemoselective isolation of aliphatic hydroxyl group-containing and aromatic hydroxyl group-containing compounds is accomplished via formation of polymeric siloxyl ethers. Chemoselective release of aliphatic hydroxyl group-containing and aromatic hydroxyl group-containing compounds from polymeric siloxyl reagents is described.
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Paragraph 0284; 0288
(2014/05/07)
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- Synthesis and biological evaluation of novobiocin analogues as potential heat shock protein 90 inhibitors
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Recent studies have shown that novobiocin (NB), a member of the coumermycin (CA) family of antibiotics with demonstrated DNA gyrase inhibitory activity, inhibits Heat shock protein 90 (HSP90) by binding weakly to a putative ATP-binding site within its C-terminus. To develop more potent HSP90 inhibitors that target this site and to define structure-activity relationships (SARs) for this class of compounds, we have synthesized twenty seven 3-amido-7- noviosylcoumarin analogues starting from NB and CA. These were evaluated for evidence of HSP90 inhibition using several biological assays including inhibition of cell proliferation and cell cycle arrest, induction of the heat shock response, inhibition of luciferase-refolding in vitro, and depletion of the HSP90 client protein c-erbB-2/HER-2/neu (HER2). This SAR study revealed that a substantial increase in biological activity can be achieved by introduction of an indole-2-carboxamide group in place of 4-hydroxy-isopentylbenzamido group at C-3 of NB in addition to removal/derivatization of the 4-hydroxyl group from the coumarin ring. Methylation of the 4-hydroxyl group in the coumarin moiety moderately increased biological activity as shown by compounds 11 and 13. Our most potent new analogue 19 demonstrated biological activities consistent with known HSP90-binding agents, but with greater potency than NB.
- Gunaherath, G.M. Kamal B.,Marron, Marilyn T.,Wijeratne, E.M. Kithsiri,Whitesell, Luke,Gunatilaka, A.A. Leslie
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p. 5118 - 5129
(2013/09/02)
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- Taming of a superbase for selective phenol desilylation and natural product isolation
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Hydroxyl moieties are highly prevalent in natural products. We previously reported a chemoselective strategy for enrichment of hydroxyl-functionalized molecules by formation of a silyl ether bond to a resin. To generate smaller pools of molecules for analysis, we developed cleavage conditions to promote stepwise release of phenolic silyl ethers followed by aliphatic silyl ethers with a "tamed" version of the superbase 1,1,3,3-tetramethylguanadine. We demonstrate this as a general strategy for selective deprotection of phenolic silyl ethers under neutral conditions at room temperature.
- Trader, Darci J.,Carlson, Erin E.
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p. 7349 - 7355
(2013/08/23)
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- Characterization of NovP and NovN: Completion of Novobiocin Biosynthesis by Sequential Tailoring of the Noviosyl Ring
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Two steps forward: The glycosylated aminocoumarin antibiotic novobiocin (1) is produced by. Streptomyces spheroides and inhibits the bacterial type II topoisomerase DNA gyrase. The sugar-tailoring enzymes NovP and NovN that catalyze the final two steps in novobiocin biosynthesis were overproduced in Escherichia coli and characterized as a methyltransferase and carbamoyltransferase, respectively.
- Meyers, Caren L. Freel,Oberthuer, Markus,Xu, Hui,Heide, Lutz,Kahne, Daniel,Walsh, Christopher T.
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- Steroid derived antibiotics
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A series of novel steroid derivatives are described. The steroid derivatives are antibacterial agents. The steroid derivatives also act to sensitize bacteria to other antibiotics including erythromycin and novobiocin.
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- Steroid derived antibiotics
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A series of novel steroid derivatives are described. The steroid derivatives are antibacterial agents. The steroid derivatives also act to sensitize bacteria to other antibiotics including erythromycin and novobiocin.
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- Steroid derived antibiotics
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A series of novel steroid derivatives are described. The steroid derivatives are antibacterial agents. The steroid derivatives also act to sensitize bacteria to other antibiotics including erythromycin and novobiocin.
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- Method for treating inflammation
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A method of treating inflammation comprising topical administration to mammals suffering from an inflammatory condition not associated with amicrobial component, employing selected antibiotics as the anti-inflammatory agent.
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