- Prodrugs of L-Cysteine as Protective Agents against Acetaminophen-Induced Hepatotoxicity. 2-(Polyhydroxyalkyl)- and 2-(Polyacetoxyalkyl)thiazolidine-4(R)-carboxylic Acids
-
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.
- Roberts, Jeanette C.,Nagasawa, Herbert T.,Zera, Richard T.,Fricke, Robert F.,Goon, David J. W.
-
-
Read Online
- Bromodimethylsulfonium bromide (BDMS) mediated dithioacetalization of carbohydrates under solvent-free conditions
-
A variety of diethyl dithioacetals of sugars can be prepared in very good yields by the reaction of various monosaccharides with ethanethiol in the presence of 3 mol % bromodimethylsulfonium bromide (BDMS) at 0-5 °C. Similarly, dipropyl dithioacetal derivatives can also be obtained in good yields using propanethiol under identical reaction conditions. These dithioacetal derivatives were characterized by per-O-acetylation using silica gel-supported perchloric acid. The significant features of the present protocol are good-to-excellent yields, mild, clean, and solvent-free reaction conditions. This method is extremely suitable for the large-scale preparation of dithioacetal derivatives of various sugars.
- Khan, Abu T.,Khan, Md. Musawwer
-
-
Read Online
- The invention of radical reactions. Part XXXVI. Synthetic studies related to 3-deoxy-D-manno-2-octulosonic acid (KDO)
-
An application of the Barton ester based radical reactions in carbohydrate chemistry is described. The chain-elongation reaction with ethyl α-trifluoroacetoxy acrylate 2, followed by treatment with phenylhydrazine provided 3-deoxy-α-hydrazono-octulosonates 8a,b derivatives of KDO and its gluco-isomer in good yield.
- Barton,Jaszberenyi,Liu,Shinada
-
-
Read Online
- Regioselective Synthesis of Difluorinated C-Furanosides Involving a Debenzylative Cycloetherification
-
A highly regioselective synthesis of valuable gem-difluorinated C-furanosides from unprotected aldoses via a debenzylative cycloetherification (DBCE) reaction induced by diethylaminosulfur trifluoride is descibed. The scope and limitations of this DBCE reaction are described using a series of commercially available pentoses and hexoses to afford, without selective protection/deprotection sequences, the corresponding gem-difluorinated C-furanosides in moderate to good yields.
- Delbrouck, Julien A.,Bochatay, Valentin N.,Tikad, Abdellatif,Vincent, Stéphane P.
-
supporting information
p. 5562 - 5566
(2019/08/01)
-
- Efficient and regioselective synthesis of γ-lactone glycosides through a novel debenzylative cyclization reaction
-
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.
- Delbrouck, Julien A.,Tikad, Abdellatif,Vincent, Stéphane P.
-
supporting information
p. 9845 - 9848
(2018/09/10)
-
- Dapagliflozin impurity synthesis method
-
The invention discloses a dapagliflozin impurity synthesis method. The synthesis method includes: using D-glucose as a raw material; subjecting the D-glucose to reactions of aldehyde group protection through ethanethiol, benzyl group adding, ethanethiol removal, condensation and benzyl group removal to obtain dapagliflozin impurities. A basis is provided for study of dapagliflozin related substances.
- -
-
Paragraph 0004; 0018-0020
(2017/03/14)
-
- 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
-
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
- Tsutsui, Nozomi,Tanabe, Genzoh,Gotoh, Genki,Morita, Nao,Nomura, Naohisa,Kita, Ayako,Sugiura, Reiko,Muraoka, Osamu
-
p. 945 - 959
(2014/02/14)
-
- Synthesis of 2,3,4,5-tetra-O-methyl-D-glucono-1,6-lactone as a monomer for the preparation of copolyesters
-
2,3,4,5-Tetra-O-methyl-D-glucono-1,6-lactone has been prepared as a crystalline compound in acceptable yield by two different routes. An initial assay of copolymerization with L-lactide by ring-opening polymerization was carried out. The incorporation of the carbohydrate monomer into the polymer chain was about 2%.
- Molina Pinilla, Inmaculada,Bueno Martinez, Manuel,Galbis, Juan A.
-
p. 549 - 555
(2007/10/03)
-
- Liquid-Crystalline D-Glucose Dialkyl Acetals and Dodecyl D-Glucofuranosides
-
Two new systems of liquid crystalline glucose derivatives 5a-d, 6a, b are prepared, studied and compared with reference compounds.The α- and β-D-dodecyl glucofuranosides 6a, b show smectic A phases.The clearing points of the furanosides are of the same magnitude as those of the pyranosides.The alkyl glucose acetals 5a-d show columnar discotic phases.The clearing points are about 30 deg C lower than those of the corresponding thioacetals. - Key Words: Acetals / Amphiphiles / Carbohydrates / Glucosides / Liquid crystals
- Tietze, Lutz F.,Boege, Kai,Vill, Volkmar
-
p. 1065 - 1068
(2007/10/02)
-
- A new synthesis of 2,5-anhydro-D-mannose derivatives
-
Penta-O-acetyl-D-glucose diethyl dithioacetal monoxide 3 was obtained by oxidation of penta-O-acetyl-D-glucose diethyl dithioacetal 2 with 3-chloroperbenzoic acid.By reaction of 3 with sodium methoxide in methanol and further acetylation, 3,4,6-tri-O-acetyl-2,5-anhydro-D-mannose-diethyl dithioacetal monoxide 8 and the reduction product 3,4,6-tri-O-acetyl-2,5-anhydro-1,1-bis(ethylthio)-1-deoxy-D-arabino-hex-1-enitol 4 were obtained.Reduction of 8 yielded the corresponding dithioacetal derivate 9, which was converted to 3,4,6-tri-O-acetyl-2,5-anhydro-D-mannose diethyl acetal 11.
- Sastre, Juan A. Lopez,Molina, Jose Molina,Olea, Dolores Portal,Romero-Avila, Cristina
-
p. 2975 - 2980
(2007/10/02)
-
- Liquid Crystalline Carbohydrate Dithioacetals
-
Various S,S-dialkyl acetals of hexanal and numerous aldoses, tripodal in structure, have been synthesized,characterized and investigated by optical microscopy and D.S.C.Most of these geminal dithioacetals show a complicated melting behaviour and are thermotropic liquid crystalline, exhibiting only one smectic-like phase of identical type.This mesophase is not miscible with the SAd-Phase of other amphiphilic sugar-based liquid crystals.As shown in a homologues series of D-glucose S,S-dialkylacetal derivatives clearing points are rising as function of growing number n of carbon atoms in their S-alkyl chains.With constant n given a similar trend is observed by varying the length of the polar, hydrophilic sugar units.Regarding stereochemistry the dithioderivatives 5 and 12 of the pentose or hexose series, respectively, with a configuration related to that of D-mannose exhibit relatively the most stable mesophase.However, the most stable mesophase of all investigated sugar dithioderivatives is exhibited by the heptose S,S-dialkylacetal 13.Surprisingly, derivative 10 of L-rhamnose (6-desoxy-L-mannose) - the terminal hydroxyl group in the sugar chain of mannose is missing! - showed to be non-mesomorphic, demonstrating that a terminal hydroxyl group of these sugar derivatives seems to be essential for exhibiting a mesophase.On the other hand, as shown with the dithioderivative 9 of 2-desoxy-D-glucose in comparison to the derivative 8e and 12 of D-glucose or D-mannose, respectively, their clearing points seem to be less, although differently effected if an internal hydroxyl group - for instance here at C-2 - has been stripped off.Melting behaviour as well as thermomesogenic properties of the presented amphiphilic carbohydrate liquid crystals in relationship to their molecular structure are discussed in detail. - Key words: Aldoses, Liquid Crystals, Mesophases, Sugar S,S-Dialkyl Acetals, Tripodal Amphiphiles
- Eckert, Andreas,Kohne, Bernd,Praefcke, Klaus
-
p. 878 - 888
(2007/10/02)
-
