92420-89-8Relevant academic research and scientific papers
Studies in sugar chemistry VII. Glucuronides of podophyllum derivatives
Nudelman, Abraham,Ruse, Margaretta,Gottlieb, Hugo E.,Fairchild, Craig
, p. 285 - 289 (1997)
The antitumor activities of several glucuronide methyl esters of podophyllum derivatives were tested in vitro against two human tumor cell lines and their drug resistant sublines. The most active compound studied was methyl (4'-carbobenzoxy-4'-demethyl- epipodophyllotoxin-D-glucopyranoside)uronate 19. Compound 19 was as potent in a colon carcinoma model and was twice as potent in a lung carcinoma model as etoposide 6. In vivo, however, in a mouse leukemia P388 model, it had only marginal activity, with a maximum T/C% value of 125 at 37 mg/kg (iv).
Crystal polymorphism of Methyl 2,3,4-tri-O-acetyl-1-O- (trichloroacetimidoyl)-α-d-glucopyranouronate
Hayes, John A.,Eccles, Kevin S.,Elcoate, Curtis J.,Daly, Carla A.,Lawrence, Simon E.,Moynihan, Humphrey A.
, p. 138 - 143 (2013)
The polymorphism of the glycoside donor methyl 2,3,4-tri-O-acetyl-1-O- (trichloroacetimidoyl)-α-d-glucopyranouronate (1) has been investigated. Two polymorphic forms (labelled Forms I and II) have been elucidated and fully characterised by DSC, PXRD and single crystal analysis, both crystallizing in the space group P21. Form I was obtained by crystallization from a wide range of solvents, while Form II was obtained only from ethyl acetate or isopropanol on certain occasions. Unit cell dimensions for Form I are a 14.0292(12), b 8.9641(8), c 16.8580(14) A, β 94.285(2), and for Form II a 11.266(3), b 6.8889(17), c 13.921(4) A, β 101.161(6). Z' is 2 for Form I and 1 for Form II. Form I displays two moderate intermolecular hydrogen bonds in the unit cell whereas Form II shows no moderate hydrogen-bonding motifs. All three molecules in the two polymorphs differ significantly in their conformations, especially with respect to the methyl carboxylate and trichloroacetimidoyl groups.
Stereoselective O-Glycosylations by Pyrylium Salt Organocatalysis**
Nielsen, Michael Martin,Holmstr?m, Thomas,Pedersen, Christian Marcus
supporting information, (2021/12/30)
Despite many years of invention, the field of carbohydrate chemistry remains rather inaccessible to non-specialists, which limits the scientific impact and reach of the discoveries made in the field. Aiming to increase the availability of stereoselective
Efficient Synthesis of Muramic and Glucuronic Acid Glycodendrimers as Dengue Virus Antagonists
García-Oliva, Cecilia,Cabanillas, Alfredo H.,Perona, Almudena,Hoyos, Pilar,Rumbero, ángel,Hernáiz, María J.
supporting information, p. 1588 - 1596 (2020/02/05)
Carbohydrates are involved in many important pathological processes, such as bacterial and viral infections, by means of carbohydrate-protein interactions. Glycoconjugates with multiple carbohydrates are involved in multivalent interactions, thus increasing their binding strengths to proteins. In this work, we report the efficient synthesis of novel muramic and glucuronic acid glycodendrimers as potential Dengue virus antagonists. Aromatic scaffolds functionalized with a terminal ethynyl groups were coupled to muramic and glucuronic acid azides by click chemistry through optimized synthetic strategies to afford the desired glycodendrimers with high yields. Surface Plasmon Resonance studies have demonstrated that the compounds reported bind efficiently to the Dengue virus envelope protein. Molecular modelling studies were carried out to simulate and explain the binding observed. These studies confirm that efficient chemical synthesis of glycodendrimers can be brought about easily offering a versatile strategy to find new active compounds against Dengue virus.
Extended scaffold glucuronides: En route to the universal synthesis of O -aryl glucuronide prodrugs
Walther, Raoul,Jarlstad Olesen, Morten T.,Zelikin, Alexander N.
supporting information, p. 6970 - 6974 (2019/08/01)
We demonstrate that an extended scaffold based on a self-immolative linker (SIL) enables the universal production of O-aryl glucuronide prodrugs: high yield glucuronidation is performed on a precursor substrate (SIL) and the subsequent drug conjugation proceeds via less challenging chemical reactions.
PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS
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Page/Page column 20; 21, (2016/11/14)
Isolated or pure compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including but not limited to psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Hunti
Synthesis of 3′-deoxy-3′-fluorothymidine (FLT) 5′-O-glucuronide: A reference standard for imaging studies with [ 18F]FLT
Harnor, Suzannah J.,Rennison, Tommy,Galler, Martin,Cano, Celine,Griffin, Roger J.,Newell, David R.,Golding, Bernard T.
, p. 984 - 988 (2014/07/08)
Reaction of methyl 2,3,4-tri-O-acetyl-1-O-(trichloroacetimidoyl)-α-d- glucopyranuronate with 3′-deoxy-3′-fluorothymidine in the presence of trimethylsilyl trifluoromethanesulfonate gave (2R,3R,4S,5S,6S)-2-(((2R,3S,5R) -3-fluoro-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl) tetrahydrofuran-2-yl)methoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4, 5-triyl triacetate, which was hydrolysed to 3′-deoxy-3′- fluorothymidine-5′-glucuronide. Analysis of this reference standard by high performance liquid chromatography enabled the identification of [ 18F]3′-deoxy-3′-fluorothymidine-5′-glucuronide in blood samples from six human patients who had been administered [ 18F]3′-deoxy-3′-fluorothymidine.
Preparation and characterisation of solid state forms of paracetamol-O-glucuronide
Hayes, John A.,Eccles, Kevin S.,Lawrence, Simon E.,Moynihan, Humphrey A.
experimental part, p. 108 - 112 (2012/03/22)
The synthesis and crystallisation of the pharmaceutically important metabolite, paracetamol-O-glucuronide, is described. Hydrated and anhydrous forms of the target molecule have been characterised by PXRD, DSC and TGA. In addition, a methanol solvate has
Synthesis and biological evaluation of prodrugs based on the natural antibiotic duocarmycin for use in ADEPT and PMT
Tietze, Lutz F.,Schmuck, Kianga,Schuster, Heiko J.,Mueller, Michael,Schuberth, Ingrid
experimental part, p. 1922 - 1929 (2011/04/15)
Chemotherapy of malign tumors is usually associated with serious side effects as common anticancer drugs lack selectivity. An approach to deal with this problem is the antibody-directed enzyme prodrug therapy (ADEPT) and the prodrug monotherapy (PMT). Her
SnCl4- and TiCl4-catalyzed anomerization of acylated O - And S -glycosides: Analysis of factors that lead to higher α: β d reaction rates
Pilgrim, Wayne,Murphy, Paul V.
supporting information; experimental part, p. 6747 - 6755 (2010/12/25)
The quantification of factors that influence both rates and stereoselectivity of anomerization reactions catalyzed by SnCl4 and TiCl4 and how this has informed the synthesis of α-O- and α-S-glycolipids is discussed. The SnCl4-catalyzed anomerization reactions of β-S- and β-O-glycosides of 18 substrates followed first order equilibrium kinetics and kf + kr values were obtained, where kf is the rate constant for the forward reaction (β → α) and kr is the rate constant for the reverse reaction (α → β). Comparison of the kf + k r values showed that reactions of glucuronic acid or galacturonic acid derivatives were ～10 to 3000 times faster than those of related glucoside and galactopyranoside counterparts and α:β ratios were generally also higher. Stereoelectronic effects contributed from galacto-configured compounds were up to 2-fold faster than those of corresponding glucosides. The introduction of groups, including protecting groups, which are increasingly electron releasing generally led to rate enhancements. The anomerization of S-glycosides was consistently faster than that of corresponding O-glycosides. Reactions were generally faster for reactions with TiCl4 than those with SnCl4. Anomeric ratios depended on the Lewis acid, the number equivalents of the Lewis acid, temperature, and substrate. Very high ratios of α-products for both O- and S-glucuronides were observed for reactions promoted by TiCl4; for these substrates TiCl4 was superior to SnCl4. Anomeric ratios from anomerization of S-glucosides were higher with SnCl4 than with TiCl4. The dependence of equilibrium ratio on Lewis acid and the number of equivalents of Lewis acid indicated that the equilibrium ratio is determined by a complex of the saccharide residue bound to the Lewis acid and not the free glycoside. The high α:β ratios observed for anomerization of both O- and S-glycuronic acids can be explained by coordination of the C-1 heteroatom and C-6 carbonyl group of the product to the Lewis acid, which would enhance the anomeric effect by increasing the electron-withdrawing ability of the anomeric substituent and lead to an increase in the proportion of the α-anomer. Such an observation would argue against the existence of a reverse anomeric effect. Support for a chelation-induced endocyclic cleavage mechanism for the anomerization is provided by the trapping of a key intermediate. The data herein will help predict the tendency of β-glycosides to undergo anomerization; this includes cases where 1,2-trans glycosides are initial products of glycosidation reactions catalyzed by TiCl4 or SnCl4.
