Reactions of metal tert-butoxides with aromatic sulfonyl chlorides. A new synthesis of di-tert-butyl ether

Di-tert-butyl ether was synthesized in good yields by the S_N reactions of lithium tert-butoxide with tosyl and p-bromobenzenesulfonyl chlorides under mild conditions.     

Effect of hydrophobic amino acids on the conformational change of decapeptides in micellar environments

A series of peptides containing various hydrophobic amino acids [methionine (Met), leucine (Leu), norleucine (Nle), phenylalanine (Phe), 2-aminooctanoic acid (Aoc), and 2-aminodecanoic acid (Ade)] were synthesized and their conformations were studied using circular dichroism (CD) spectroscopy in different solvents such as water, methanol, and aqueous solution of ammonium tetradecanesulfonate. Peptides containing hydrophobic amino acids with linear side chains formed -sheets in water and methanol. Electrostatic interaction between the charged side chain (lysine) and a micelle consisting of an anionic surfactant, ammonium tetradecanesulfonate, is necessary for the formation of -helices in micellar environments. The conformational transition from -helix to -sheet structure required moderate hydrophobicity and linear side chains. This conformational transition depended on the surfactant concentration.     

Application of samarium diiodide (SmI2)-induced reduction of gamma-acetoxy-alpha,beta-enoates with alpha-specific kinetic electrophilic trapping for the synthesis of amino acid derivatives

Gamma-acetoxy-alpha,beta-enoates were easily reduced by samarium diiodide (SmI2) in THF to generate samarium dienolates which were kinetically trapped with ease at their alpha-positions by electrophiles (proton, aldehydes or ketones) to yield (E)-alkene dipeptide isosteres or gamma-amino acid derivatives in high chemical yields.     

SmI2-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates with application to the synthesis of functionalized (Z)-fluoroalkene-type dipeptide isosteres

A samarium diiodide (SmI(2))-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the gamma,gamma-difluoro-alpha,beta-enoates by SmI(2) proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to alpha-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI(2)-HCHO reagent system with chiral enoate 34 provided D-Phe-psi[(Z)-CF[double bond]CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the alpha-position. This was achieved by a sequence of manipulations consisting of beta-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of alpha,alpha-difluoro-beta-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.     

Sepharose derivatives containing citric acid as affinity ligand. Purification of fumarase

Six Sepharose derivatives, in which citrate was immobilized via methylene carbons, were prepared by coupling of the alpha- and beta-isomers of citrylpolymethylenediamine to Sepharose. The purification of fumarase from pig heart was dependent on the length of the spacer arm, but not on the isomeric configuration of the immobilized citrate. Gels having six methylene carbons had the largest adsorption capacity for the enzyme and therefore were the most suitable for use in affinity columns for its purification. Affinity chromatography with these gels was followed by hydrophobic interaction chromatography on an octamethylenediamine-Sepharose column.     

Simple and sensitive determination of methylglyoxal in biological samples by gas chromatography with electron-capture detection

Methylglyoxal was allowed to react with 4,5-dichloro-1,2-phenylenediamine, and the 6,7-dichloro-2-methylquinoxaline formed was determined by gas chromatography with electron-capture detection. The standard curve of the quinoxaline was linear up to 160 pmol/ml. The recoveries of methylglyoxal from coffee and rat liver homogenate were 84.1 and 77.6%, respectively. This procedure was very selective and so sensitive that as little as 9 fmol of the quinoxaline could be measured in biological and food samples.     

Thermodynamically stable vesicle formation from glycolipid biosurfactant sponge phase

Thermodynamically stable vesicle (L(alpha1)) formation from glycolipid biosurfactant sponge phase (L(3)) and its mechanism were investigated using a "natural" biocompatible mannosyl-erythritol lipid-A (MEL-A)/L-alpha-dilauroylphosphatidylcholine (DLPC) mixture by varying the composition. The trapping efficiency for calcein and turbidity measurements clearly indicated the existence of three regions: while the trapping efficiencies of the mixed MEL-A/DLPC assemblies at the compositions with X(DLPC)< or =0.1 or X(DLPC)> or =0.8 were almost zero, the mixed assemblies at the compositions with 0.1 or =0.8 were multilamellar vesicles (L(alpha)) with diameter from 2 to 10 microm. Meanwhile, dynamic light scattering (DLS) measurement revealed that the average size of the vesicles at the composition of X(DLPC)=0.3 was 633.2 nm, which is remarkably small compared to other compositions. Moreover, the mixed vesicle solution at the composition of X(DLPC)=0.3 was slightly bluish and turbid and kept its dispersion stability at 25 degrees C for more than 3 months, indicating the formation of a thermodynamically stable vesicle (L(alpha1)). These results exhibited the formation of a thermodynamically stable vesicle (L(alpha1)) with a high dispersibility from the MEL-A/DLPC mixture. The asymmetric distribution of MEL-A and DLPC in the two vesicle monolayers caused by the difference in geometrical structures is very likely to have changed their self-assembled structure from a sponge phase (L(3)) to a thermodynamically stable vesicle (L(alpha1)).     

Microcomputer-aided optimal selection of control input for the precision water bath of a heat exchange calorimeter

In heat exchange calorimetry, sample and reference vessels are fixed differentially in a water bath. The heat evolved in the sample vessel is exchanged freely with the ambient water. The accuracy and precision of the calorimetry depend on the temperature range of the drift and fluctuation in the bath water. In the present report, a simple temperature-control system with no empirical factors is proposed for the precision water bath. The heat exchange between the inside of the vessels and the ambient water is expressed by a differential equation or a Newtonian cooling equation. Similarly, the thermal behaviour of a water bath placed in a non-air-conditioned laboratory was also considered to be expressed by the same equation. The heat exchanged with the surroundings, the non-stationary heat flow from warm stirrer motors, and other thermal factors were considered to be part of the heat sources. Cooling water about 2°C lower than the set temperature was circulated in the water bath. The difference between the set temperature and the observed temperature was fed into a microcomputer every second. The latest four data points were used to fit a modified Newtonian equation by the common method of least-squares. The control input to the bath was calculated and given to the heater circuit after power amplification. The program written in basic was about 3.3 kbyte. The controlled range of drift and fluctuation was almost the same, or better, as that previously reported.     

Pyrimidines. XIII. Novel pyrimidine to pyrimidine transformation reactions

Novel pyrimidine to pyrimidine transformation reactions are described. 1,3-Dimethyl-(or diethyl)-uracil(1) are converted into isocytosine, 2-thiouracil or uracil derivatives by treatment with guanidine, thiourea or urea, respectively. The latter two cases require base catalysis. The effects of some substituents at C-5 and C-6 of 1,3-dialkylated uracils (1a → 1e) on this transformation were examined and a plausible mechanism is offered for their reaction. The utility of this reaction is exemplified by the facile two-step conversion of pseudouridine into the anlileukemic agent, pseudoisocytidine, in good overall yield.