Super acid-induced Pummerer-type cyclization reaction: improvement in the synthesis of chiral 1,3-dimethyl-1,2,3,4-tetrahydroisoquinolines

Improved synthesis of four stereoisomeric chiral 1,3-dimethyl-1,2,3,4-tetrahydroisoquinolines (1a, b, ent-1a, b) was achieved via the super acid-induced cyclization of chiral N-[1-methyl-2-(phenylsulfinyl)ethyl]-N-(1-phenylethyl)formamides (4a, b, ent-4a, b) using the Pummerer-type cyclization reaction as a key step. The cyclization leading to the isoquinoline ring proceeded in a quantitative manner when trifluoromethane sulfonic acid (TFSA) was used as the super acid, although Friedel-Crafts-type alkylation of 4-phenylsulfanyl TIQ derivatives (5) with benzene used as the solvent accompanied cyclization to yield the 4-phenyl-TIQs (7). The byproduct (7) was exclusively formed when a large excess amount of TFSA was used.     

A synthesis of chiral 1,1,3-trisubstituted 1,2,3,4-tetrahydro-beta-carbolines by the Pictet-Spengler reaction of tryptophan and ketones: conversion of (1R,3S)-diastereomers into their (1S,3S)-counterparts by scission of the C(1)-N(2) bond

The Pictet-Spengler cyclization of the imines (3) prepared by the condensation of L-tryptophan methyl ester (1) and aryl methyl ketones (2), using titanium(IV) isopropoxide as an iminating reagent, quantitatively proceeded, when treated with trifluoroacetic acid (TFA) or formic acid, to provide two diastereomers, that is (1S,3S)-1-aryl-3-isopropoxycarbonyl-1-methyl-1,2,3,4-tetrahydro-beta-carbolines (4) and their (1R,3S)-diastereomers (5), of which the diastereomer ratios varied from 1 to 5 depending on the reaction conditions. The (1R,3S)-diastereomers (5) are thermodynamically more stable than their (1S,3S)-congeners (4), as shown by equilibration experiments in TFA. The conversion of 4 to 5 (also 5 to 4) should occur under acidic conditions by cleavage of the C(1)-N(2) bond with complete retention of configuration at the C-3 chiral center. The low diastereo-selectivity observed in the Pictet-Spengler reaction of 1 and 2 is concluded to be a stereochemical outcome under conditions of kinetic control (lower temperature, shorter reaction time), while the high diastereo selectivity with preferential formation of the more stable isomer (5) is the result of thermodynamically controlled experiments (higher temperature, longer reaction time).     

Melting and swelling behaviors of UV-irradiated gelatin gel microcapsules

Gelatin gel microcapsules with a narrow size distribution have been prepared for the use of regenerative therapy by means of SPG (Shirasu porous glass) emulsification and UV-induced cross linking, and the melting and swelling behaviors of the gel membrane of the microcapsules were observed. The gel melting temperature was proportional to the 2/3 power of UV irradiation time t for tor=1 h. The average cross-sectional area of the microcapsules that remains insoluble normalized by that at 25 degrees C monotonically increased with temperature for tor=1 h. Repeated quenching of the gel microcapsules between two temperatures (25 and 40 degrees C) induced a reversible size change, which was attributed to the helix-coil transition of collagen molecules locally. From a theoretical consideration of gel particles, the observed gel melting behavior was explained well, and the scaled volume of the microcapsules was expressed as a function of scaled temperature with four fitting parameters for t相似文献   

Preparation of a zwitterionic trichloroplatinum(II) complex with an alkylbipyridinum ligand and its reaction in dmso-<Emphasis Type="BoldItalic">d</Emphasis><Subscript>6</Subscript> solution

A zwitterionic trichloroplatinum(II) complex PtCl₃(4,4′-bpy-N-ⁿBu) (1) was prepared by an aqueous reaction of [4,4′-bpy-N-ⁿBu]Cl with K₂PtCl₄, and was characterized by ¹H-n.m.r. and IR spectroscopy as well as elemental analysis. Dissolving (1) into dmso-d ₆ at 25 °C yields a mixture of the complexes, cis-PtCl₂(4,4′-bpy-N-ⁿBu)(dmso-d ₆) (2-cis), trans-PtCl₂(4,4′-bpy-N-ⁿBu)(dmso-d ₆) (2-trans), [4,4′-bpy-N-ⁿBu]Cl and PtCl₂(dmso-d ₆)₂. Ratio of the products in the dmso-d ₆ solution changed depending on the temperature and the total concentration of the complexes. These compounds are in equilibrium via isomerization reaction between (2-cis) and (2-trans) and via displacement reaction of the alkylbipyridinium ligand of (2-cis) and (2-trans) with dmso-d ₆ to form [4,4′-bpy-N-ⁿBu]Cl and PtCl₂(dmso-d ₆)₂.     

Kinetic studies of CO2dissociation on supported Ni catalysts

Summary In order to investigate the kinetics of CO₂dissociation on supported nickel catalysts, a novel technique, which can give the surface reaction rate constants with no information on the number of active sites, was developed. It was revealed that CO₂dissociation was more enhanced on TiO₂support than on other metal oxide ones. The activity pattern and activation energies were in good agreement with those obtained by a conventional pulse technique using the number of active sites, suggesting the validity of the present technique for investigating the kinetics of the surface reaction.</o:p>     

Practical synthesis of a neuropeptide Y antagonist via stereoselective addition to a ketene

[Reaction: see text]. The synthesis of neuropeptide Y antagonist 1, currently under clinical investigation for the treatment of obesity, is described. The convergent synthesis from trans-spirolactone carboxylic acid intermediate 2a and aminopyrazole 3 is predicated on a stereoselective route to the former. The coupling reaction of ethyl 4-oxocyclohexanecarboxylate (10a) with lithiated isonicotinamide 11 was investigated in detail, but even optimized conditions only provided a 45:55 ratio of trans:cis isomers (12a:12b). While selective crystallization schemes were developed to isolate the thermodynamically less stable trans isomer 2a, improved stereocontrol was subsequentially achieved by the application of ketene chemistry. The ketene formation and quench was investigated under a variety of conditions aimed at maximizing the trans:cis ratio. Reacting a mixture of carboxylic acids 2a and 2b with POCl3 in THF, followed by concomitant addition of tert-butyl alcohol in the presence of TMEDA at 35 degrees C provided a 4:1 ratio of trans:cis tert-butyl esters (18a:18b) via in situ ketene formation. Ester hydrolysis, followed by selective crystallization of undesired 2b as the HCl salt, led to isolation of 2a in 47% overall yield. Aminopyrazole intermediate 3 was synthesized via the condensation reaction of 2-fluorophenylhydrazine hydrochloride (4a) with acrylonitrile derivative 5 in 65-70% yield. Coupling of advanced intermediates 2a and 3b via activation with thionyl chloride gave a 92% yield of 1.     

Interference, fluctuation, and alternation of electron tunneling in protein media. 2. Non-condon theory for the energy gap dependence of electron transfer rate

Developing the quantum transition rate theory of Prezhdo and Rossky (J. Chem. Phys. 1997, 107, 5863), we produced a new non-Condon theory of the rate of electron transfer (ET) which happens through a protein medium with conformational fluctuation. The new theory is expressed by a convolution form of the power spectrum for the autocorrelation function of the electronic tunneling matrix element T(DA)(t) with quantum correction and the ordinary Franck-Condon factor. The new theory satisfies the detailed balance condition for the forward and backward ET rates. The ET rate formula is divided into two terms of elastic and inelastic tunneling mechanisms on the mathematical basis. The present theory is applied to the ET from Bph(-) to Q(A) in the reaction center of Rhodobacter sphaeroides. Numerical calculations of T(DA)(t) were made by a combined method of molecular dynamics simulations and quantum chemistry calculations. We showed that the normalized autocorrelation function of T(DA)(t) is almost expressed by exponential forms. The calculated energy gap law of the ET rate is nearly Marcus' parabola in most of the normal region and around the maximum region, but it does not decay substantially in the inverted region, which is called the anomalous inverted region. We also showed that the energy gap law at the high uphill energy gap in the normal region is elevated considerably from the Marcus' parabola, which is called the anomalous normal region. Those anomalous energy gap laws are due to the inelastic tunneling mechanism which works actively at the energy gap far from zero. We presented an empirical formula for easily calculating the non-Condon ET rate, which is usable by many researchers. We provided experimental evidence for the anomalous inverted region which was basically reproduced by the present theory. The present theory was extensively compared with the previous non-Condon theories.     

Preparation of organic acid anion-modified magnesium hydroxides by coprecipitation: A novel material for the uptake of heavy metal ions from aqueous solutions

New layered magnesium hydroxides whose brucite layers had been bridged with malate²⁻ and tartrate²⁻ were prepared by dropwise addition of Mg(NO₃)₂ to malate and tartrate solutions at a constant pH of 10.5. Malate²⁻ and tartrate²⁻ may have been also absorbed on the surfaces of hydroxides. In the case of using citrate solution, Mg(OH)₂ absorbed with citrate³⁻ was produced. These materials were found to take up Cu²⁺ rapidly from an aqueous solution at pH 5.0. Copper uptake by precipitates is attributed to the formation of chelate complexes of Cu²⁺ with citrate³⁻, malate²⁻, and tartrate²⁻.     

The edge state of nanographene and the magnetism of the edge-state spins

Nanographene has unique edge-shape dependence of the electronic structure with non-bonding edge states being created in its zigzag edges. The presence of the edge state is experimentally confirmed in well-defined hydrogen-terminated zigzag edges by scanning tunneling microscopy/spectroscopy (STM/STS) observations. In the three-dimensional (3D) disordered network of nanographite domains in nanoporous carbon (activated carbon fibers), the localized edge-state spins are in a spin-glass-like ordered state at low temperatures with the aid of exchange interactions whose strengths varies randomly in space, when the strengths of inter-nanographene and nanographite interactions are tuned. Chemical and structural modifications of nanographene edges change the magnetism of edge-state spins through covalent bond formation and charge transfer.     

Thermally responsive wettability of self-assembled methylcellulose nanolayers

Thermo-responsive cellulosic nanolayers were prepared from methylcellulose (MC), which is known to have a unique lower critical solution temperature. Thiosemicarbazide (TSC) was selectively introduced into the MC reducing end groups, and the corresponding MC-TSC derivative was spontaneously chemisorbed on an Au substrate at 4 °C to give MC self-assembled monolayers (SAMs). Linear MC chains were stably fixed onto the Au substrate, yielding an MC-SAM of thickness ca. 15 nm with a root mean square value less than 1 nm. The MC-SAM surface exhibited thermally responsive wetting characteristics; the water contact angle was found to rise and fall around 70 °C, possibly due to the solid-state phase transition of the MC nanolayers resulting from the inherent gelation of MC molecules in water. Such wetting behavior was shown to be reversible following repeated heating and cooling. The MC-SAM immersed in salt solution revealed lower phase transition temperatures, and an increase in sodium chloride concentration ranging from 0.0 to 1.0 M brought about a dramatic decrease in the apparent phase transition temperature from ca. 70 to 30 °C. For the purposely designed MC nanolayers, such controllable wetting properties are expected to prompt growing interest in the applications of cellulosic biopolymer interfaces.