Synthesis of an electronically-tuned minimally interfering alkynyl photo-affinity label to measure small molecule–protein interactions

We report the synthesis of an electronically-tuned minimally interfering photo-affinity label (MI-PAL), a compact five-carbon tag functionalized with an alkyl diazirine and alkyne handle. MI-PAL is compatible with protein photo-conjugation, click chemistry and mass spectrometry and readily installed to complex molecules for biological target identification.     

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.

     

Synthesis of 5α-hydroxyecdysteroid analogs containing an isoxazole ring in the side chain

An analog of 5-hydroxyecdysteroids having an isoxazole ring in the side chain was synthesized starting from pregnenolone through intermediate 20-hydroxy-20-(3-isopropyl-4,5-dihydroisoxazol-5-yl) derivative. -Bromination of 6-oxo steroids was accompanied by elimination of the hydroxy group from C²⁰ and migration of the double bond thus formed to the heteroring to afford the corresponding 20-isoxazolyl steroid.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 10, 2004, pp. 1506–1510.Original Russian Text Copyright © 2004 by Litvinovskaya, Drach, Masalova, Khripach.     

Synthesis of Spirobenzopyrans Carrying a Monoaza-benzo-15-C-5 at the 8-position

SpirobenzopyranderivativesarewellknownphotochroAncorganiccompounds,whichcanbereversiblyisomerizedbyUVandvisiblelightirradiation.Whencrownmoietiesareincorporatedtothespirobenzopyrans,theymayprovidespirobenzopyranderivativeswithspecificcationbindingabilities,whichcaninduceisomerizationofthespirobenzopyrans,thusdrasticallyaffectingtheisomerizationequilibriumbetweenthespiropyranandthemerocycanineforms.Thesecrownedspirobenzopyranderivativesaremoreeffectiveforphotochemicalcontrolofphysicalpropertie…     

Synthesis of 6-aryl-2′-deoxyuridine nucleosides via a Liebeskind cross-coupling methodology

Hitherto, the synthesis of 6-substituted 2′-deoxyuridine nucleoside analogues via Pd-catalyzed Suzuki cross-coupling reaction was hampered by the instability of the TIPDS-protected precursor 6-iodo-2′-deoxyuridine 1 in alkaline media due to cleavage of the glycosidic bond. Herein, the successful application of the Liebeskind reaction under base-free conditions is reported. This method comprises of the stoichiometric use of copper thiophene carboxylate (CuTC) as co-reagent at slightly elevated temperatures. Fluoride-mediated desilylation and Yoshikawa-phosphorylation afforded the nucleotide analogues 4b–c, 4e, and 4i.     

Direct introduction of a benzoyloxy substituent at the C-4 position of β-lactams

The copper-promoted reaction of β-lactams with t-butyl perbenzoate results in benzoyloxylation of the azetidin-2-one ring at the C-4 position. There is no competing reaction at the C-3 position, but reaction at exocyclic carbon α to nitrogen competes with ring substitution.     

Synthesis of the diazepanone-nucleoside portion of liposidomycins by aldol reaction of the enolate of diazepanone with a nucleoside 5′-aldehyde

The diazepanone-nucleoside part of liposidomycins has been synthesized by the aldol reaction between the enolate of a stereochemically defined diazepanone and a uridine 5′-aldehyde. The configurations of two new stereocenters in the aldol product have been assigned on the basis of the ¹H NMR coupling constants and NOE of its derivative.     

Investigation of unanticipated alkylation at the N(π) position of a histidyl residue under Mitsunobu conditions and synthesis of orthogonally protected histidine analogues

We had previously reported that Mitsunobu-based introduction of alkyl substituents onto the imidazole N(π)-position of a key histidine residue in phosphothreonine-containing peptides can impart high binding affinity against the polo-box domain of polo-like kinase 1. Our current paper investigates the mechanism leading to this N(π)-alkylation and provides synthetic methodologies that permit the facile synthesis of histidine N(π)-modified peptides. These agents represent new and potentially important tools for biological studies.     

Synthesis of guanidines via the I2 mediated desulfurization of N,N′-di-Boc-thiourea

The I₂ mediated desulfurization of N,N′-di-Boc-thiourea was developed. Various primary amines, including sterically and electronically deactivated primary amines, were transformed into the corresponding bis-Boc protected guanidines under mild conditions.     

Synthesis of Crystalline Nanosized Titanium Dioxide via a Reverse Micelle Method at Room Temperature

Crystalline TiO2 nanoparticles were synthesized by hydrolysis of titanium tetrabutoxide in the presence of hydrochloric acid in Np-5(lgepal CO-520)/ cyclohexane reverse micelle solution at room temperature.Pure rutile nanoparticles were obtained at an appropriate acid concentration.The influences of various reaction conditions such as the concentration of acids,water content value (2=[H2O]/[Np-5]) on the formation,erystal phase,morphology,and size of the TiO2 particles were investigated.     

Synthesis of linear unsubstituted poly(4,4′-triphenylamine) via Suzuki-Miyaura coupling of an asymmetric AB monomer

Polytriarylamines (PTAAs) are amorphous polymers that can be reversibly oxidized to generate stable radical cations. Despite exhibiting a low charge carrier mobility, PTAAs are widely used as hole-transporting layers in perovskite solar cells due to their excellent stability under ambient conditions. The highest occupied molecular orbital (HOMO) energy levels of PTAA are generally in the range of −5.1 to −5.2 eV, and therefore slightly too high for an optimal alignment with perovskites. Most linear PTAAs carry two or three methyl substituents per repeating unit. While these prevent crosslinking of chains and thus provide reaction control, the electron-donating substituents raise the energy level of the HOMO. Unsubstituted PTAA on the other hand is usually obtained crosslinked via oxidative polymerization, while nickel-catalyzed Grignard polycondensation leads to inclusion of impurities. We report the synthesis of linear unsubstituted PTAA using Suzuki-Miyaura coupling of a novel asymmetric monomer, 4-((4-bromophenyl)(phenyl)amino)phenyl)boronic acid M1 . Based on matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and ¹H NMR analysis, we can conclude that the hydrogen-terminated linear polymer is obtained. The determined HOMO energy level of −5.47 eV is a favorable match for many perovskite systems.     

Hydrothermal and Solvothermal Synthesis of the Complex Fluoride α′-SrAlF_5

Introduction　　Strontiumaluminumpentafluoride SrAlF5isagoodhostforthespectralresearchofdopedrareearthionsduetoitsweakcrystalfieldenvironment.Forthefirsttime ,Hewesetal.1foundthef→flineemissionoftheEu2 + inSrAlF5matrix ,andfournonequivalentsitesforRE2 + inSrAlF5havealsobeenreported .2 Theobservationofthetunable laserofCr3+ from 85 2to 94 7nminSrAlF5hasat tractedconsiderableattention3andtheferroelectricbehav ior4 ofSrAlF5hasextendeditsapplicablefield .Twogener almethods,high temperatur…     

Hydrothermal and Solvothermal Synthesis of the Complex Fluoride α′-SrAIF5

The complex fluoride α′-SrAlF5 has been synthesized through hydrothermal and solvothermal methods under mild conditions.The effects of the molar ratio of starting materials,temperature,reaction time and solvents on the synthesis of α′-SrAlF5 were discussed.The final products were characterized by XRD and SEM.The rod-like shape of α′-SrAlF5 is shown in SEM images.     

A convenient and general approach to the synthesis of properly protected d-nucleoside-3′-hydrogenphosphonates via phosphite intermediates

Evidence will be presented to show that the monofunctional phosphitylating reagents bis(N,N-di-ethylamino)chlorophosphine and salicylchlorophosphine are very effective for the preparation of 5′-0,N-protected d-nucleoside-3′-hydrogenphosphonates.     

Synthesis and bioactivity of α-galactosylceramide analogues bearing an aryl group within the fatty amide chain

We describe the synthesis and bioactivity of analogues of α-galactosylceramide (1) bearing a long-chain alkyl group substituted at the meta or para position of an aryl group embedded within the amide chain. We compared the ability of these compounds and of 1 and C6Ph (2, which has a phenyl group at the amide chain terminus) to stimulate murine invariant Natural Killer T cells and to dock with human CD1d.     

Investigations into the electrooxidation of guanosine-5′-triphosphate at the pyrolytic graphite electrode

The electrochemical oxidation of guanosine-5-triphosphate has been investigated in phosphate-containing electrolytes in the pH range 1.5–10.9 at a pyrolytic graphite electrode by cyclic sweep voltammetry, spectral studies, bulk electrolysis and related techniques. In this pH range, the oxidation occurred in a single well-defined peak (I_a). The peak potential of oxidation peaks (E_p) was found to be dependent on pH, concentration and sweep rate. The kinetics of the UV-absorbing intermediates was followed spectrophotometrically and the decay of the intermediate occurred in a pseudo-first-order reaction. The first-order rate constants for the disappearance of the UV-absorbing intermediate have also been calculated. The products of the electrode reaction were characterized by HPLC and GC/MS. A tentative mechanism for the formation of the products has also been suggested.