Substituent and solvent effects on the tautomer ratios between the hydrazone imine and diazenyl enamine forms in p- and m-substituted 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines

The p- and m-substituted 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines 1a-i and 2a-d exhibited tautomeric equilibria between the hydrazone imine A and diazenyl enamine B forms in a series of mixed dimethyl sulfoxide/trifluoroacetic acid media. The substituent and solvent effects on the tautomer ratios of A to B in a series of mixed media were studied for compounds 1a-i and 2a-d by the nmr spectroscopy. The linear correlation of the Hammett σp and σm values with the tautomeric equilibrium constants K_T ([A]/[B]) was found in the dimethyl sulfoxide media of compounds 1a-i and 2b-d . On the other hand, the linear correlation of the Hammett σp and σm values with the log C'(A:B = 1:1) was also observed in a series of mixed media of compounds 1a-h and 2a-c , wherein C'(A:B = 1:1) indicated the concentrations of trifluoroacetic acid (mol/l) giving 1:1 tautomer ratios in a series of mixed media. The increase in the Hammett σp or σm values decreased the K_T values in dimethyl sulfoxide media and augmented the C'(A:B = 1:1) values in a series of mixed media. The Hammett σp or σm values controlled the electron density of the side chain nitrogen atom, which influenced the C'(A:B = 1:1) values. In the K_T value temperature dependence, the higher temperature provided the larger K_T values in dimethyl sulfoxide media regardless of the Hammett σp or σm values.     

Highly stereoselective asymmetric Pummerer reactions that incorporate intermolecular and intramolecular nonbonded S...O interactions

New chiral sulfoxides (R(S),S)-3, (S(S),S)-3, (R(S),S)-4, and (S(S),S)-4 and known chiral sulfoxides (R(S))-5, (R(S))-6, and (R(S))-7 were synthesized, and the stereochemistry of the new sulfoxides (R(S),S)-3 and (R(S),S)-4 was determined by X-ray crystallographic analysis. In their crystallographic structures, the intramolecular nonbonded S...O close contacts were recognized. Analyses of several sulfoxide complexes including rac-11 with N,N-dimethylacetamide (DMAC) or N-methyl-2-pyrrolidone (NMP) in a MeOH solution utilizing cold-spray ionization mass spectrometry provided, for the first time, direct information for intermolecular nonbonded S...O interactions between sulfoxides and amide (or lactam) in a solution. Highly diastereoselective and enantioselective Pummerer reactions based on the concept of intermolecular and intramolecular nonbonded S...O interactions were performed by treatment of several chiral sulfoxides (R(S), S)-3, (S(S), S)-3, (R(S), S)-4, (S(S), S)-4, (R(S))-5, (R(S))-6, and (R(S))-7 with acetic anhydride and trimethylsilyl triflate (TMSOTf) in DMAC, NMP, N,N-dimethylformamide, and N-formylpiperidine. Mechanistic studies on these facile stereoselective Pummerer reactions revealed the necessity for the amide/TMSOTf complex, such as 26 or 27, to be an efficient activation reagent for Ac(2)O and a trapping reagent for the released acetate ion, and that DMAC and NMP had a positive effect on this highly stereoselective chiral transfer reaction.     

Two new antitumor diterpenes from Pinus sylvestris

Two new diterpenes, 15-ethyl-18-methyl pinifolate （1） and 18-hydroxy-labda-8（17）, 13E-dien-15-acetate （2）, were isolated from the needles of Pinus sylvestris. Their structures were elucidated by spectroscopic methods, including 2D-NMR spectra. Compound 1 exhibited the significant cytotoxic activity against the human carcinoma cell lines Hela, SK-N-SH and BEL-7402 in vitro.     

Pressure and temperature-controlled enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylate mediated by secondary face- and skeleton-modified gamma-cyclodextrins

A series of secondary-face-substituted and skeleton-modified gamma-cyclodextrins (gamma-CDs) were prepared as chiral hosts for enantiodifferentiating [4+4] photocyclodimerization reactions of 2-anthracenecarboxylic acid (AC). These gamma-CD derivatives form stable ternary complexes with ACs, with altroside-bearing gamma-CDs undergoing induced-fit conformational changes upon complexation, and the photocyclodimerization of AC was, thus, dramatically accelerated. The enantiomeric excess (ee) of anti-head-to-head cyclodimer 3 was greatly enhanced in general with altroside-bearing gamma-CDs 7-9. Although mono-altro-gamma-CD 9 and 3A-azido-3A-deoxy-altro-gamma-CD 7 gave 2 in ee's smaller than those obtained with native gamma-CD, 3A-amino-3A-deoxy-altro-gamma-CD 8 yielded 2 in much higher ee's, which is likely to be ascribed to the combined effects of the less-symmetric cavity and the electrostatic interactions. The influence of temperature and high pressure on the supramolecular photochirogenic reaction has been investigated in depth. An ee as high as 71% was obtained for cyclodimer 2 in the photocyclodimerization of AC mediated by 8 at 210 MPa and -21.5 degrees C.     

Chemical constituents from Sambucus adnata and their protein-tyrosine phosphatase 1B inhibitory activities

The MeOH extract from the whole plants of Sambucus adnata has shown significant protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity. Chemical study on the extract resulted in the isolation of thirteen compounds, including a novel triterpene (1). The structure of 1 was determined to be 1α,3β-dihydroxy-urs-12-en-11-one-3-yl palmitate on the basis of extensive spectroscopic analyses. Among the isolated compounds, ursolic acid, oleanolic acid and (±)-boehmenan showed the most potent PTP1B inhibitory activity in vitro with the IC(50) values of 4.1, 14.4 and 43.5 μm, respectively. The kinetic analysis indicated that (±)-boehmenan inhibits PTP1B activity in a competitive manner.     

A facile synthesis of enol type acyl cyanides via a 1,3-dipolar cycloaddition reaction and a cyano group migration

The reaction of 7-chlorotetrazolo[1,5-a]quinoxaline 5-oxide 4a or 7-chloro-1,2,4-triazolo[4,3-a]quinoxaline 5-oxide 4b with 2-chloroacrylonitrile gave 7-chloro-4-(2-cyano-2-hydroxyvinyl)tetrazolo[1,5-a]quinoxaline 5a or 7-chloro-4-(2-cyano-2-hydroxyvinyl)-1,2,4-triazolo[4,3-a]quinoxaline 5b , respectively. Alcoholysis of compound 5a or 5b afforded 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydrotetrazolo[1,5-a]quinoxaline 6a or 7-chloro-4-ethoxycarbonylmethylene-4,5-dihydro-1,2,4-triazolo[4,3-a]quinoxaline 6b , respectively. Compounds 5a,b were found to exist as a syn and anti mixture of the enol form, while compounds 6a,b occurred as the enamine and methylene imine forms. The tautoraeric character and/or D-H exchange of the vinyl protons are described for compounds 5a,b and 6a,b .     

Doubly activated supramolecular reaction: transesterification of acyclic oligoether esters with metal alkoxides

Transesterification reactions of acyclic oligoether esters E3-E10 with metal alkoxides were accelerated upon noncovalent complexation of the esters with metal ions. In the reaction of monovalent alkaline metal alkoxides, CH(3)ONa and CH(3)OK, plots of the observed rate constants k(obs) with respect to the chain length of E3-E10 showed selective acceleration of the transesterification. Compared with the shortest E3, which can hardly bind metal ion, 4.3- and 6.6-fold accelerations in the maxima were achieved in the combinations of E5/CH(3)ONa and E6/CH(3)OK, respectively. Supramolecular intermediate complex could be spectrometrically visualized by ESI-FT-ICR-MS in the course of reaction. Kinetic experiments, together with structural analyses by means of NMR, mass spectrometry, and DFT calculations of the intermediate complexes, indicate that a size-fit complex of host substitute with alkali metal ion allows strong electron withdrawing due to the close contact of the carbonyl oxygen to the metal ion, resulting in the selective rate enhancement of the reaction, while in the reaction of E3-E10 with a divalent alkaline earth metal alkoxide, (CH(3)CH(2)O)(2)Ba, the k(obs) values increased stepwise with elongation of the side arm to attain an dramatic large acceleration. In comparison with the k(obs) of E3, 4610-fold acceleration was achieved in the reaction of E10. The double activation of the host substrate and guest counter nucleophile at once brings about this extraordinary rate acceleration. The strong wrapping complexation of long oligoether ester with barium ethoxide allows for the effective electron withdrawal from the ester carbonyl group (host activation) as well as separation of the accompanying guest alkoxide anions (guest activation).     

Effects of thermal history on enthalpy relaxation

The effects of the thermal history on enthalpy relaxation in polymethylmethacrylate (PMMA) have been studied by differential scanning calorimetry (DSC). The temperature dependence of specific heat capacity in the liquid and glassy states, that of relaxation time and the exponent of the Kohlrausch–Williams–Watts function have been obtained by the measurement of the response of heat flux to the sinusoidal temperature variation. The phenomenological model equation as an extension of linear rheology has been applied to enthalpy relaxation. The evolution of entropy under a given thermal history same as the experiment has been calculated and compared with the DSC results. The calculated results reproduce two peaks of specific heat capacity at lower and higher temperatures in the glass transition region: the former is characteristic of PMMA and the latter is observed in typical glassy polymers.     

Enantiodifferentiating photoisomerization of (Z,Z)-1,3-cyclooctadiene included and sensitized by naphthoyl-curdlan

6-O-(2-naphthoyl)curdlan was newly synthesized as a sensitizing polysaccharide host to examine the chiroptical properties, supramolecular complexation, and photochirogenic behavior with (Z,Z)-1,3-cyclooctadiene (1ZZ). The enantiodifferentiating photoisomerization of 1ZZ included and sensitized by this polysaccharide host gave a highly strained chiral (E,Z)-isomer in up to 8.7% enantiomeric excess (ee) in solution and 11.7% ee in the solid state, which are the highest values ever reported for a supramolecular photochirogenesis of 1EZ.     

A New Hemiterpene Derivative from Prinsepia utilis

Prinsepia utilis Royle is shrub plant growing at an altitude of 1000-2500 m in south ofChina and India1. It has been used in folk medicine to treat various skin diseases andrheumatism2. The hydrocyanic acid3 and fatty oil4 have been isolated from this pla…