1941-52-2Relevant articles and documents
Prodrugs of L-Cysteine as Protective Agents against Acetaminophen-Induced Hepatotoxicity. 2-(Polyhydroxyalkyl)- and 2-(Polyacetoxyalkyl)thiazolidine-4(R)-carboxylic Acids
Roberts, Jeanette C.,Nagasawa, Herbert T.,Zera, Richard T.,Fricke, Robert F.,Goon, David J. W.
, p. 1891 - 1896 (1987)
Eight prodrugs of L-cysteine (1a-h) were synthesized by the condensation of the sulfhydryl amino acid with naturally occurring aldose monosaccharides containing three, five, and six carbon atoms.The resulting 2-(polyhydroxyalkyl)thiazolidine-4(R)-carboxylic acids (TCAs) are capable of releasing L-cysteine and the sugars by nonenzymatic ring opening and hydrolysis.Thus, when added to rat hepatocyte preparations in vitro, these TCAs (1.0 mM) raised cellular gluthatione (GSH) levels 1.2-2.1-fold relative to controls.On the basis of this finding, the cysteine prodrugs were tested as protective agents against acetaminophen-induced hepatotoxicity in a mouse model.The TCA derived from D-ribose and L-cysteine (RibCys, 1d) showed the greatest therapeutic promise of the series, with a 100percent (12/12) survival profile compared to 17percent without treatment.However, the degree of stimulation of GSH production in rat hepatocytes by these prodrugs did not correlate with the extent of protection afforded in mice, suggesting that pharmacokinetic parameters must supervene in vivo.To evaluate the effect of increased lipid solubility, we prepared prodrugs 2a-c by using peracetylated aldehydic sugars in the condensation reaction.These compounds, however, displayed acute toxicity to mice, possibly due to liberation of the acetylated sugars themselves.Nevertheless, the efficacy of the unacetyleted TCAs, and RibCys (1d) in particular, suggests that the prodrug approach for the delivery of L-cysteine to the liver represents a viable means of augmenting existing detoxication mechanisms in protecting cells against xenobiotic substances that are bioactivated to toxic, reactive metabolites.
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Wolrom,Georges
, p. 282,285 (1937)
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The nitrous acid deamination of 2-amino-2-deoxy-d-mannose hydrochloride to d-glucose
Horton, Derek,Philips, Kerstin D.,Defaye, Jacques
, p. 417 - 419 (1972)
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Efficient and regioselective synthesis of γ-lactone glycosides through a novel debenzylative cyclization reaction
Delbrouck, Julien A.,Tikad, Abdellatif,Vincent, Stéphane P.
supporting information, p. 9845 - 9848 (2018/09/10)
An efficient and regioselective approach for the construction of synthetically important γ-lactone glycosides is reported from unprotected aldoses through a new debenzylative lactonization (DBL) reaction. The scope and limitations of this DBL reaction are described starting from a series of commercially available hexoses (l-fucose, d-galactose, d-glucose) and pentoses (d-arabinose, d-ribose, d-lyxose, d-xylose) to afford the corresponding γ-lactones in good yields and without concomitant δ-lactone formation.
Structure-activity relationship studies on acremomannolipin A, the potent calcium signal modulator with a novel glycolipid structure 2: Role of the alditol side chain stereochemistry
Tsutsui, Nozomi,Tanabe, Genzoh,Gotoh, Genki,Morita, Nao,Nomura, Naohisa,Kita, Ayako,Sugiura, Reiko,Muraoka, Osamu
, p. 945 - 959 (2014/02/14)
Five alditol analogs 1b-1f of a novel glycolipid acremomannolipin A (1a), the potential Ca2+ signal modulator isolated from Acremonium strictum, were synthesized by employing a stereoselective β-mannosylation of appropriately protected mannose with five hexitols with different stereochemistry, and their potential on modulating Ca2+ signaling were evaluated All these analogs were more potent compared to the original compound 1a, and proved that mannitol stereochemistry of 1a was not critical for the potent calcium signal modulating
