A novel synthesis of N-acetyl-α-d-fucosamine 1-phosphate and uridine 5"-diphospho-N-acetyl-α-d-fucosamine

In connection with studies on the biosynthesis of capsular polysaccharides from Staphylococcus aureus, a new synthesis of uridine 5"-(2-acetamido-2,6-dideoxy--d-galactopyranosyl diphosphate) (uridine 5"-diphospho-N-acetyl--d-fucosamine) using 2-azido-3,4-di-O-acetyl-2,6-dideoxy--d-galactopyranosyl nitrate as the key intermediate was carried out. The reaction of this product with cesium dibenzyl phosphate smoothly affords the corresponding -glycosyl dibenzyl phosphate, which undergoes anomerization on treatment with BF₃·Et₂O and 2-bromopyridine to give -glycosyl dibenzyl phosphate in high yield. This product was then transformed into 2-amino-3,4-di-O-acetyl-2,6-dideoxy--d-galactopyranosyl phosphate, subsequently converted into 2-acetamido-2,6-dideoxy--d-galactopyranosyl phosphate and the target nucleoside diphosphate sugar.     

The first chemical synthesis of pyrazofurin 5′-triphosphate

As an archetype C-nucleoside, pyrazofurin possesses broad-spectrum antiviral and antitumor activities. However, the presence of the acidic enol in the nucleobase of pyrazofurin poses a huge challenge to the conventional NTP synthetic methods. On the basis of a selective phosphorylation method and the P(V)-N activation strategy, the first chemical synthesis of pyrazofurin 5′-triphosphate (PTP) was accomplished, which will greatly facilitate the investigation on the interactions of viral RNA polymerases and PTP, an important cellular metabolite of pyrazofurin.     

Simple and effective method for the synthesis of 3′,5′-substituted 1-β-D-arabinofuranosyluracil

3,5-Substituted arabinofuranosyluracil is a starting compound in 2-modifications. A convenient and effective method is proposed for the synthesis of 1-(3,5-di-o-trityl--D-arabinofuranosyl)uracil by successive reactions of 2,2-cyclization of uridine, 3,5-tritylation of the 2,2-anhydrouridine, and hydrolytic cleavage of the 2,2-anhydro bond.Institute of Organic Synthesis, Riga LV-1006. Odense Universitet, Kemisk Institut, Odense, Denmark. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 975–977, July, 1996. Original article submitted April 25, 1996.     

Stereoselective synthesis of 5′-hydroxyzearalenone

A first stereoselective total synthesis of 14-memebered β-resorcylic macrolactone 5′-hydroxyzearalenone (1) has been achieved. The key steps are Jocobsen hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylation, Vilsmeier-Haack reaction, Mitsunobu esterification and ring-closing metathesis.     

Chemical transformations of pyridoxal and pyridoxal 5′-phosphate condensation products with amino acids

The mechanism of chemical transformations of pyridoxal and pyridoxal 5′-phosphate condensation products with amino acids is studied by kinetic measurements. The Schiff bases are shown to be fairly stable in neutral media. In acid media, the Schiff bases are hydrolyzed into the initial components. In alkaline media, cleavage of α-hydrogen from the amino acid fragment and structural rearrangement into the quinoid form followed by hydrolysis of the latter with elimination of pyridoxamine and keto acid take place. The rate constants of the chemical transformations of the Schiff bases are found to depend on the pH of the medium. It is shown for the first time that the phosphate group in the pyridoxal 5′-phosphate fragment catalyzes the α-hydrogen cleavage and strongly accelerates alkaline decomposition of the Schiff bases.     

Incompatibility of acid-labile 2′ and 5′ protecting groups for solid-phase synthesis of oligoribonucleotides

Cleavage of 2−O-tetrahydropyranyl groups from ribonucleoside derivatives used in solid-phase oligoribonucleotide synthesis takes place to an unacceptable extent during treatment with protic acid to remove 5′-O-pixyl groups.     

Some new derivatives of Cr(III) with uracil,uridine and 5′-UMP

Some new Cr(III) compounds with uracil, uridine and 5′-UMP were obtained by reaction of the starting complexes cis-[Cr(en)₂Cl₂]Cl and [Cr(NH₃)₅Cl]Cl₂ with the base, nucleoside and nucleotide. The complexes were characterized by their elemental analysis, conductivity, reflectance and IR data. In the case of uracil and uridine compounds, indirect bonding of Cr(III) to the pyrimidine ring seems to occur through the C₄O and NH₃(NH₂) groups of the starting complexes. In the 5′-UMP complex direct bonding is inferred through the phosphate group with additional interactions by hydrogen bonds involving the C₄O group.     

The synthesis of (R)-2′,3′-dihydroxypropyl 5-deoxy-5-dimethylarsinoyl-β-D-riboside,a naturally-occurring,arsenic-containing carbohydrate

The synthesis of (R)-2′,3′-dihydroxypropyl 5-deoxy-5-dimethylarsinoyl-β-D-riboside is reported.     

Supramolecular Tandem Assay for Pyridoxal-5′-phosphate by the Reporter Pair of Guanidinocalix[5]Arene and Fluorescein

Guanidinocalix[5]arene and fluorescein reporter pair has been chosen to set up a supramolecular tandem assay principle based on the differential recognition of pyridoxal-5′-phosphate (the substrate of alkaline phosphatase, ALP), pyridoxal (the product of ALP) and phosphate (the product of ALP). This supramolecular tandem assay system offers an opportunity to monitor the activity of ALP in a label-free, continuous, and real-time manner. More importantly, a calibration curve can be given for selective and quantitative detection of pyridoxal-5′-phosphate (biomarker for several diseases).     

Synthesis and properties of novel 4-(diarylmethyl)pyridines based on pyridoxal 5′-phosphate

Russian Chemical Bulletin - The reaction pyridoxal 5′-phosphate with resorcinols in EtOH in the presence of concentrated HCl gives hydrochlorides of the corresponding...     

Synthesis of some 5′-O-amino acid derivatives of uridine as potential inhibitors ofUDP-glucuronosyltransferase

Summary In an attempt to develop potential inhibitors ofUDP-glucuronosyltransferase, some 5-O-amino acid derivatives of uridine were synthesized. N-protectedL-amino acids were coupled at the 5-O-position of 2,3-O-isopropylideneuridine by esterification employing the method of symmetrical anhydrides in presence of 4-dimethylaminopyridine, 5-O-(N-benzyloxycarbonyl-O-tert.butyl-L-threonl)-23-O-isopropylideneuridine (1), 5-O-(N-tert.butyloxycarbonyl-O-benzyl-L-seryl)-2,3-O-isopropylideneuridine and (2), 5-O-(N-tert.butyloxycarbonyl-L-valyl)-2,3-O-isopropylideneuridine (3), and 5-O-(N-tert.butyloxycarbonyl-L-valyl)-2,3-O-isopropylideneuridine (4) were obtained in good yield after column chromatography on silica gel. The treatment of2 withTFA/CH₂Cl₂ (6:1) at room temperature for 30 min led to a selective removal of theBoc group without deblocking of the 2,3-O-isopropylidene group of uridine. Treatment of2 withTFA/H₂O (5:1) at room temperature for 1 h, however, released bothBoc and 2,3-isopropylidene groups. TheZ group of1 was deprotected by catalytic hydrogenolysis over 10% Pd/C/ammonium formate.

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Synthese von 5-O-Aminosäurederivaten des Uridins als potentielle Inhibitoren derUDP-Glukuronosyl-Transferase

Zusammenfassung In einem Versuch, potentielle Inhibitoren derUDP-Glukuronosyl-Transferase zu entwickeln, wurden einige 5-O-Aminosäurederivate des Uridins synthetisiert. N-GeschützteL-Aminosäuren wurden durch Veresterung mit der 5-O-Position des 2,3-isopropylidenuridins gekuppelt (Methode der symmetrischen Anhydride in der Gegenwart von 5-Dimethylaminopyridin). Solcherweise wurden 5-O-(N-Benzyloxycarbonyl-O-tert.butyl-L-threonly)-2,3-O-isopropylidenuridin (1), 5-O-(N-tert.Butyloxycarbonyl-O-benzyl-L-seryl)-2,3-O-isopropylidenuridin (2), 5-O-(N-tert.Butyloxycarbonyl-L-leucyl)-2,3-O-isopropylidenuridin (3) und 5-O-(N-tert.Butyloxycarbonyl-L-valyl)-2,3-O-isopropylidenuridine (4) nach Säulenchromatographie (Kieselgel) in guter Ausbeute hergestellt. Die Behandlung von2 mitTFA/CH₂Cl₂ (6:1) bei Zimmertemperatur (30 min) führte zu einer selektiven Abspaltung derBoc-Gruppe ohne Deblockierung der 2,3-O-Isopropylidengruppe des Uridins. Eine Behandlung von2 mitTFA/H₂O (5:1) bei Zimmertemperatur für 1 Stunde führte hingegen zur Abspaltung sowohl derBoc als auch der 2,3-O-Isopropylidengruppe. DieZ-Gruppe von1 wurde durch katalytische Hydrogenolyse auf 10% Pd/C/Ammoniumformiat abgespalten.

     

Schiff bases formed between pyridoxal 5′-phosphate and Amino-β-cyclodextrins: Intramolecular remote ion pair interactions of the phosphate with ammonium moieties

Abstract

Equilibria involved in the Schiff base formations of pyridoxal 5′-phosphate (PLP) and 5′-deoxypyridoxal with mono-, di-, and peraminocyclodextrins have been studied to determine equilibrium binding constants in aqueous media at several pH values. These results, as well as the circular dichroism study, show that remote electrostatic interactions between the negatively charged 5′-phosphate group and a second ammonium group on the cyclodextrins play a significant role in the complexation.     

Selective synthesis and optical properties of diimidazo[1,2-a:5′,1′-c]quinoxaline derivatives

Novel diimidazo[1,2-a:5′,1′-c]quinoxaline derivatives were synthesized by a Pd-catalyzed intramolecular coupling reaction of 1,2-bis(2-iodo-1H-imidazol-1-yl)benzene. This method was applied to the selective introduction of an aryl substituent at the 10 position by the addition of a boronic ester. Moreover, a stepwise introduction of the aryl substituent could be achieved by the further coupling reaction at the 3 position. Focused on the optical properties, a more efficient substituent effect at the 10 position was obtained compared with the analogous structure, diimidazo[1,2-a:2′,1′-c]quinoxaline derivatives. In addition, we revealed that the diimidazo[1,2-a:5′,1′-c]quinoxaline skeleton potentially has an electron-donating character on the optical properties by introducing an electron-withdrawing substituent.     

Stereoselective synthesis of 1-O-β-feruloyl and 1-O-β-sinapoyl glucopyranoses

1-O-β-Feruloyl and 1-O-β-sinapoyl glucopyranoses are two common substrates for serine carboxypeptidase-like acyltransferases and serve as acyl donors in the biosynthesis of numerous secondary metabolites. In addition, they are involved in plant cell wall cross-linking and are also ideal substrates for studying the kinetics of lignification involving hydroxycinnamates. We report the first chemical (and multi-gram scale) synthesis of 1-O-β-feruloyl and 1-O-β-sinapoyl glucopyranoses.     

Chemical 5′-phosphorylation of oligonucleotidesvaluable in automated DNA synthesis

A new method has been developed for the chemical 5′-phosphorylation ofoligonucleotides starting from easily available phosphorous-III compounds using phosphate protecting groups which can be cleaved off via β-elimination. The hydrophobic 2-(p-nitrophenyl)-ethyl group, at the phosphodiester level can serve as a purification handle in reversed phase HPLC. Moreover, the procedure has been adapted to automated DNA synthesis.     

Highly polarized enamines 1. synthesis and some properties ofβ-tetrazolylenamines

A method has been developed for the synthesis of some-tetrazolyl--nitroenamines containing various alkoxy or amino substituents in the a position. It is based on the transformation of a pyrimidine ring by sodium azide.Center for Drug Chemistry, All-Union research Institute of Pharmaceutical Chemistry (VNIKhFI), Moscow 119021 Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 976–980, July, 1994