Synthesis of 1-(3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranosyl)uracils via an α,β-unsaturated aldehydrohexose

Summary Mercuric catalyzed hydrolysis of acetylatedL-rhamnal1 gave the ,-unsaturated aldehyde2. 1,2,4-Triazole was coupled, in a Michael type addition reaction, to2 at C-3 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give, after acetylation at the anomeric center, an anomeric mixture of 1,5-di-O-acetyl-3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranose (3). Reaction of3 with silylated 2,4-dihydroxypyrimidines4 in the presence of trimethylsilyl triflate as catalyst followed by deprotection with 33% methylamine in absolute ethanol afforded the corresponding nucleosides7 and8.

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Synthese von 1-(3-(1,2,4-Triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranosyl)uracilen über eine ,-ungesättigte Aldohexose

Zusammenfassung Die quecksilberkatalysierte Hydrolyse von acetyliertemL-Rhamnal1 ergab die ,-ungesättigten Aldehyde2. 1,2,3-Triazol wurde in Gegenwart von 1,8-Diazabicyclo[5.4.0]-7-undecen mittels einer Addition vom Michael-Typ an C-3 von2 gekoppelt und ergab dann nach Acetylierung am anomeren Zentrum eine anomere Mischung von 1,5-Di-O-acetyl-3-(1,2,4-triazol-1-yl)-2,3,6-trideoxy-L-arabino-hexofuranose (3). Die Reaktion von3 mit silyliertem 2,4-Di-hydroxypyrimidinen4 in Gegenwart von Trimethylsilyltriflat in absolutem Ethanol ergab die entsprechenden Nucleoside7 und8.

     

Diastereomeric Oxathia[n](1,1′)ferrocenophanes

Zusammenfassung Neue Oxathiaferrocenophane wurden durch Umsetzung von 1,1-Bis(hydroxymethyl)ferrocen mit Dithiolen dargestellt, welche Sauerstoff in den Alkylketten enthalten. Die Reaktion von 1,1-Bis(-hydroxyethyl)ferrocenen mit Dithiolen führte zu Mischungen von Diastereomeren, aus welchen reine Stereoisomere isoliert und charakterisiert wurden. Einige Aspekte des stereochemischen Verlaufes dieser Reaktionen werden diskutiert.

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Diastereomere oxathia[n](1,1)ferrocenophane

Novel oxathiaferrocenophanes have been synthesized by the reaction of 1,1-bis(hydroxymethyl)ferrocene with dithiols bearing oxygen in chains. The reactions of 1,1-bis(-hydroxyethyl)ferrocenes with dithiols afforded mixtures of diastereomeric products from which pure stereoisomers were isolated and characterized. Some aspects concerning a stereochemical course of the reactions described are discussed.

     

Synthesis,structures, and conformational characteristics of calixarene monoanions and dianions

The synthesis, complete characterization, and solid state structural and solution conformation determination of calix[n]arenes (n = 4, 6, 8) is reported. A complete series of X-ray structures of the alkali metal salts of calix[4]arene (HC4) illustrate the great influence of the alkali metal ion on the solid state structure of calixanions (e.g., the Li salt of monoanionic HC4 is a monomer; the Na salt of monoanionic HC4 forms a dimer; and the K, Rb, and Cs salts exist in polymeric forms). Solution NMR spectra of alkali metal salts of monoanionic calix[4]arenes indicate that they have the cone conformation in solution. Variable-temperature NMR spectra of salts HC4.M (M = Li, Na, K, Rb, Cs) show that they possess similar coalescence temperatures, all higher than that of HC4. Due to steric hindrance from tert-butyl groups in the para position of p-tert-butylcalix[4]arene (Bu(t)C4), the alkali metal salts of monoanionic Bu(t)C4 exist in monomeric or dimeric form in the solid state. Calix[6]arene (HC6) and p-tert-butylcalix[6]arene (Bu(t)C6) were treated with a 2:1 molar ratio of M(2)CO(3) (M = K, Rb, Cs) or a 1:1 molar ratio of MOC(CH(3))(3) (M = Li, Na) to give calix[6]arene monoanions, but calix[6]arenes react in a 1:1 molar ratio with M(2)CO(3) (M = K, Rb, Cs) to afford calix[6]arene dianions. Calix[8]arene (HC8) and p-tert-butylcalix[8]arene (Bu(t)()C8) have similar reactivity. The alkali metal salts of monoanionic calix[6]arenes are more conformationally flexible than the alkali metal salts of dianionic calix[6]arenes, which has been shown by their solution NMR spectra. X-ray crystal structures of HC6.Li and HC6.Cs indicate that the size of the alkali metal has some influence on the conformation of calixanions; for example, HC6.Li has a cone-like conformation, and HC6.Cs has a 1,2,3-alternate conformation. The calix[6]arene dianions show roughly the same structural architecture, and the salts tend to form polymeric chains. For most calixarene salts cation-pi arene interactions were observed.     

SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS–XVI. ISPERSE BLUE 35

The photochemistry (Type I and II) of the phototoxic textile dye Disperse Blue (DB-35) and its purified components has been studied using electron spin resonance in conjunction with spin trapping technique and the direct detection of singlet oxygen (1O2) luminescence. The main components of DB-35 (which is synthesized by the successive nitration, reduction and methylation of 1,8-dihydroxy-anthraquinone) were separated by HPLC and identified by mass spectrometry and 2-D NMR as 4,5-diamino-1,8-dihydroxyanthraquinone (4,5-DDHAQ; 62% of total dye) and 2,7-diamino-1,8-dihydroxyanthraquinone (2,7-DDHAQ; 31% of total dye). Minor components included 2,5-diamino-1,8-dihydroxyanthraquinone (2,5-DDHAQ) and a monomethylated derivative of either 4,5-DDHAQ or 2,7-DDHAQ. Irradiation (624 nm) of 4,5-DDHAQ and 2,7-DDHAQ in dimethylsulfoxide resulted in the generation of superoxide which was trapped by 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Visible light irradiation of the components in ethanol generated 1O2 with the yields decreasing in the following order: 4,5-DDHAQ greater than 2,5-DDHAQ greater than 2,7-DDHAQ. These findings indicate that upon irradiation by visible light DB-35 can generate active oxygen species which may be responsible for the photocontact dermatitis caused by this dye.     

Spectroscopic and thermodynamic characterization of the E151D and E151A altered leucine aminopeptidases from Aeromonas proteolytica

Previous kinetic characterization of the glutamate 151 (E151)-substituted forms of the leucine aminopeptidase from Aeromonas proteolytica (Vibrio proteolyticus; AAP) has provided critical evidence that this residue functions as the general acid/base. The close proximity of similar glutamate residues to the bridging water/hydroxide of the dinuclear active sites of metalloenzymes (2.80 and 3.94 angstroms in carboxypeptidase G2 and 3.30 and 3.63 angstroms in AAP), suggests it may also be involved in stabilizing the active-site metal ions. Therefore, the structural perturbations of the dinuclear active site of AAP were examined for two E151-substituted forms, namely E151D-AAP and E151A-AAP, by UV-vis and electron paramagnetic resonance (EPR) spectroscopy. UV-vis spectroscopy of Co(II)-substituted E151A-AAP did not reveal any significant changes in the electronic absorption spectra. However UV-vis spectra of mono- and dicobalt(II) E151D-AAP exhibited a lower molecular absorptivity compared to AAP (23 and 43 M(-1) cm(-1) vs. 56 and 109 M(-1) cm(-1) for E151D-AAP and AAP, respectively) suggesting both Co(II) ions reside in distorted octahedral coordination geometry in E151D-AAP. EPR spectra of [Co_(E151D-AAP)], [ZnCo(E151D-AAP)], and [(CoCo(E151D-AAP)] were identical, with g(perpendicular) = 2.35, g(parallel) = 2.19, and E/D = 0.19, similar to [CoCo(AAP)]. On the other hand, the EPR spectrum of [Co_(E151A-AAP)] was best simulated assuming the presence of two species with (i) g(x,y) = 2.509, g(z) = 2.19, E/D = 0.19, A = 0.0069 cm(-1) and (ii) g(x,y) = 2.565, g(z) = 2.19, E/D = 0.20, A = 0.0082 cm(-1) indicative of a five- or six-coordinate species. Isothermal titration calorimetry experiments revealed a large decrease in Zn(II) affinities, with K(d) values elevated by factors of approximately 850 and approximately 24,000 for the first metal binding events of E151D- and E151A-AAP, respectively. The combination of these data indicates that E151 serves to stabilize the dinuclear active site of AAP.     

Structure and thermodynamic aspects of macrobicyclic polyether-metal ion interactions

The crystals structure of a K⁺-diptychand-15C5-18C6 iodide complex has been determined from X-ray data. The complexed bicyclic molecule crystallizes in the triclinic space group witha = 9.995(4) Å,b = 10.097(4) Å,c = 13.725(6) Å, = 90.12(3)°, = 93.62(4)°, = 97.56(3)°. The structure was solved using heavy atom methods and refined toR = 0.032 for 3262 independent reflections. In the crystal structure, the K⁺ lies between the two crown ether rings, and is coordinated by the nine donor atoms of the ligand molecule. The complexation properties of the ligand with K⁺ and Na⁺ were studied by titration calorimetry in 90% (v/v) MeOH/H₂O solution. The studies indicate the formation of 1 : 1 ligand : metal ion complexes in both solid state and solution.This paper is dedicated to the memory of the late Dr C. J. Pedersen.     

Reaction of Nitroxides with Sulfur Containing Compounds II [1]. Preparation of Nitroxides Bearing an Isothiocyanate Substituent in View of the Nitroxyl Group Reduction with Thiophosgene

 The reaction of thiophosgene with 2,2,6,6-tetramethylpiperidine-1-oxyl (used as a model nitroxyl radical) was examined. 2,2,6,6-Tetramethylpiperidine and 2,2,6,6-tetramethyl-1-hydroxypiperidine were identified as products. The reaction is not competitive with the reaction of thiophosgene with an amino group. Thus, three nitroxides with an isothiocyanate group were synthesized from thiophosgene and the nitroxides containing the amino substituent.     

A concerted mechanism for the transfer of the thiophosphinoyl group from aryl dimethylphosphinothioate esters to oxyanionic nucleophiles in aqueous solution

Earlier work on the hydrolysis of aryl phosphinothioate esters has led to contradictory mechanistic conclusions. To resolve this mechanistic ambiguity, we have measured linear free energy relationships (beta(nuc) and beta(lg)) and kinetic isotope effects for the reactions of oxyanions with aryl dimethylphosphinothioates. For the attack of nucleophiles on 4-nitrophenyl dimethylphosphinothioate, beta(nuc) = 0.47 +/- 0.05 for phenoxide nucleophiles (pK(a) < 11) and beta(nuc) = 0.08 +/- 0.01 for hydroxide and alkoxide nucleophiles (pK(a) >or= 11). Linearity of the plot in the range that straddles the pK(a) of the leaving group (4-nitrophenoxide, pK(a) 7.14) is indicative of a concerted mechanism. The much lower value of beta(nuc) for the more basic nucleophiles reveals the importance of a desolvation step prior to rate-limiting nucleophilic attack. The reactions of a series of substituted aryl dimethylphosphinothioate esters give the same value of beta(lg) with the nucleophiles HO(-) (beta= -0.54 +/- 0.03) and PhO(-) (beta = -0.52 +/- 0.09). A significantly better Hammett correlation is obtained with sigma(-) than with sigma or sigma degrees , as expected for a transition state involving rate-limiting cleavage of the P-OAr bond. The (18)O KIE at the position of bond fission ((18)k = 1.0124 +/- 0.0008) indicates the P-O bond is approximately 40% broken, and the (15)N KIE in the leaving group ((15)k = 1.0009 +/- 0.0003) reveals the nucleofuge carries about a third of a negative charge in the transition state. Thus, both the LFER and KIE data are consistent with a concerted reaction and disfavor a stepwise mechanism.     

Photooxidation of Methionine Derivatives by the 4-Carboxybenzophenone Triplet State in Aqueous Solution. Intracomplex Proton Transfer Involving the Amino Group

Abstract— Oxidation of the triplet state of 4-carboxybenzophenone (CB) by a series of five substituted methionines and three methionine-containing dipeptides was monitored under laser flash photolysis conditions in aqueous solution. Spectral resolution techniques were employed to follow the concentration profiles of the intermediates formed from the quenching events. From these concentration profiles, quantum yields for the intermediates were determined. Branching ratios were evaluated for the decay of the charge-transfer complex by the competing processes of back electron transfer, proton transfer and escape of radical ions. The relative prominence of these processes was discussed in terms of the proton-transfer tendencies of the nominal sulfur-radical-cationic species. A systematic decrease was observed in the quantum yields for the escape of radical ions along with a correlated increase in the proton-transfer yields. The enhanced propensity of the sulfur radical cations to depro-tonate is due to deprotonation at the carbons adjacent to the sulfur-cationic site and at the unsubstituted amino groups when present. This scheme was supported by an observed decrease in the yields of dimeric sulfur radical cations with an increase in the electron-withdrawing abilities of the substituents, making the radical-cationic species stronger acids. The involvement of protons on the amino groups was implicated by the correlation of the quantum yields of ketyl radical formation in the photochemistry experiments with the rate constants for the reaction of the CB radical anion with the sulfur-containing substrates in pulse radiolysis experiments.