Synthesis and biological evaluation of RON-neoglycosides as tumor cytotoxins

Langenhan, Joseph M.; Endo, Matthew M.; Engle, Jeffrey M.; Fukumoto, Liane L.; Rogalsky, Derek R.; Slevin, Lauren K.; Fay, Lindsay R.; Lucker, Ryan W.; Rohlfing, James R.; Smith, Kyle R.; Tjaden, Anja E.; Werner, Halina M.

doi:10.1016/j.carres.2011.09.019

Cited by 26 publications

(56 citation statements)

References 54 publications

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“…We also checked the influence of the nature of the oxyamine. O-Benzylhydroxylamine 18 generally resulted in similar yields and reaction rates compared to ethoxyamine 11 ( Table 1, entries [16][17][18][19]. Also the acyclic to cyclic ratio is similar with slightly higher amounts of the cyclic product.…”

Section: Variation Of the Sugar And Oxyaminementioning

confidence: 82%

“…[8a] Application of secondary oxyamines 7 circumventst his problem because they provide exclusively cyclic N-glycosides (Scheme 1). Therefore, secondary oxyamines have been applied in the preparation of neoglycosphingolipids, [16] therapeutic neoglycoconjugates, [17] in the formation of glycosyl acceptors in enzymatic synthesis, [18] for the immobilization on glass slides, [8b, 19] or in the preparation of mucin analogues. [20] Investigationof reaction products of secondary alkylhydroxylamines 7 showedt hat cyclic pyranosides 9 andf uranosides 10 can be formed depending on the carbohydrate used.…”

Section: Introductionmentioning

confidence: 99%

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Real‐Time NMR Studies of Oxyamine Ligations of Reducing Carbohydrates under Equilibrium Conditions

Baudendistel

Wieland

Schmidt

et al. 2016

Chemistry A European J

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Ligation reactions at the anomeric center of carbohydrates have gained increasing importance in the field of glycobiology. Oxyamines are frequently used in labeling, immobilization, and bioconjugation of reducing carbohydrates. Herein, we present a systematic investigation of these ligation reactions under aqueous conditions. A series of four unprotected monosaccharides (glucose, N-acetylglucosamine, mannose, and 2-deoxyglucose) and one disaccharide (N,N'-diacetylchitobiose) was reacted with three primary and one secondary oxyamine. We monitored the concentrations of the starting materials and products by 1 H NMR spectroscopy and determined reaction times and equilibrium yields. Our experiments show that the outcome of the ligation reaction is not only dependent on the sugar and oxyamine used but also strongly on the reaction conditions. In the case of glucose, lowering the pH from 6 to 3 led to steadily increasing reaction rates, whereas the yields were decreasing at the same time. Variation of the temperature did not only influence the product ratio in equilibrium but can also have a strong impact on the equilibrium yield. In the case of reactions of a primary oxyamine, increased temperatures led to a higher proportion of acyclic products. Reaction of the secondary oxyamine with glucose unexpectedly led to lower yields at higher temperatures.

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Section: Variation Of the Sugar And Oxyaminementioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Real‐Time NMR Studies of Oxyamine Ligations of Reducing Carbohydrates under Equilibrium Conditions

Baudendistel

Wieland

Schmidt

et al. 2016

Chemistry A European J

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show abstract

“…[161] Langenhan et al investigated the structures obtained for ar ange of glycosyl O-methyl-N-(4-methylbenzyl) oxyamines. [162] Interestingly,N ,O-dialkyl glycosyl oxyamines are not confined to the b-anomericc onfiguration. Rather,t he thermodynamically most stable configurations are determined by the nature of the monosaccharide unit, similar to glycosylo ximes (Scheme40).…”

Section: No-dialkyl N-glycosyl Oxyaminesmentioning

confidence: 99%

“…The thermodynamically most stable structures of N-glycosyl-Omethyl oxyamines dependo nt he monosaccharide unit. Redrawn from Langenhan et al [162] ChemBioChem 2017, 18,574 -612 www.chembiochem.org that the reactionp roceeded via glycosylidene aziridine [172] intermediates before putative formation of an oxocarbenium ion, which then reacted with the alcohol (Scheme 42). Nitz and co-workerss howed that the reactions could be performed with unprotectedc arbohydrates, under milder conditions, and in the absence of strong base.…”

Section: N-glycosyl Sulfonylhydrazides As Glycosyl Donorsmentioning

confidence: 99%

Chemoselective Reactions for the Synthesis of Glycoconjugates from Unprotected Carbohydrates

et al. 2017

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Glycobiology is the comprehensive biological investigation of carbohydrates. The study of the role and function of complex carbohydrates often requires the attachment of carbohydrates to surfaces, their tagging with fluorophores, or their conversion into natural or non-natural glycoconjugates, such as glycopeptides or glycolipids. Glycobiology and its "omics", glycomics, require easy and robust chemical methods for the construction of these glycoconjugates. This review gives an overview of the rapidly expanding field of chemical reactions that selectively convert unprotected carbohydrates into glycoconjugates through the anomeric position. The discussion is divided in terms of the anomeric bond type of the newly formed glycoconjugates, including O-, N-, S-, and C-glycosides.

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“…27 However, they concluded that the glycoside structure had a larger influence on cytotoxicity than the alkoxygroup. 83 This model was also used to explore the impact of nucleophilic catalysts to speed the neoglycosylation reaction. 84 A subsequent study to assess the impact of the length of the digitoxose saccharide chain for both O - and MeON-glycosides of digitoxin towards cytotoxicity revealed the monodigitoxoside to be the best in both formats.…”

Section: Section 4 – Natural Product and Small Molecule Drug Discovermentioning

confidence: 99%

Neoglycosylation and neoglycorandomization: enabling tools for the discovery of novel glycosylated bioactive probes and early stage leads

Goff

Thorson

2014

Med. Chem. Commun.

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This review focuses upon the development, scope, and utility of the highly versatile chemoselective alkoxyamine-based ‘neoglycosylation’ reaction first described by Peri and Dumy. The fundamentals of neoglycosylation and the subsequent development of a ‘neoglycorandomization’ platform to afford differentially-glycosylated libraries of plant-based natural products, microbial-based natural products, and small molecule-based drugs for drug discovery applications are discussed.

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Synthesis and biological evaluation of RON-neoglycosides as tumor cytotoxins

Cited by 26 publications

References 54 publications

Real‐Time NMR Studies of Oxyamine Ligations of Reducing Carbohydrates under Equilibrium Conditions

Real‐Time NMR Studies of Oxyamine Ligations of Reducing Carbohydrates under Equilibrium Conditions

Chemoselective Reactions for the Synthesis of Glycoconjugates from Unprotected Carbohydrates

Neoglycosylation and neoglycorandomization: enabling tools for the discovery of novel glycosylated bioactive probes and early stage leads

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