Keiichi Aoe

Synthesis and crystal structure of a new c2-symmetric chiral bis-sulfoxide ligand and its palladium(ii) complex

Abstract A new chiral bis-sulfoxide ligand (S,S)-1,2 bis(p-tolylsulfinyl)benzene (BTSB), which possesses S,S bidentate chelating donor atoms on an aromatic ring, was synthesized. Pd, Rh, and Ru readily gave adducts with this ligand. The crystal structure of PdCl2[btsb-S,S′]·2(C6H6) showed that this ligand had C2-symmetric S-coordination. Moderate asymmetric induction was observed in the Pd-catalyzed allylic substitution using BTSB as a ligand.

Enantioselective Cu-catalyzed 1,4-addition of Me3Al to a 4,4-disubstituted cyclohexa-2,5-dienone

Abstract A series of chiral enantiomerically pure 2-aryloxazolines was synthesized. (4 S )-2-(2′,6′-dimethoxyphenyl)-4-isopropyloxazoline proved to be an efficient chiral ligand for the Cu-catalyzed conjugate addition of Me 3 Al to cyclohexadienone, and by using 20mol% of this ligand, 1,4-adduct was obtained in 68% ee. In addition, TBDMSOTf is crucial for the asymmetric conjugate addition to proceed with good chemical yield and high ee.

Analysis of β-lactam antibiotics by high performance liquid chromatography–atmospheric pressure chemical ionization mass spectrometry using bromoform

The novel identification method for a heat-unstable antibiotic, FC/TA-891 and its active metabolite (FCE22101) by high-performance liquid chromatography (HPLC)-atmospheric pressure chemical ionization mass spectrometry (APCI-MS) employing bromoform as an ionization acceleration solvent, was applied to eight penicillins and 13 cephalosporins which are groups of beta-lactam antibiotics. The conditions of HPLC-APCI-MS were examined with ampicillin. Bromoform or chloroform was added to the mobile phase in HPLC to compare the difference between bromine and chlorine adducted ions. For all penicillins except sulbenicillin, both chlorine adducted and bromine adducted ions were observed with a flow injection method. The results indicated that the relative sensitivity ratios of bromine adducted ions to [M-H](-) were higher than those of chlorine adducted ions. These bromine adduct ions could be clearly distinguished from other ions due to its isotopical ratio (1:1), leading to an easy identification of the compounds. For 13 cephalosporins, bromine adducted ions were detected in nine compounds, and chlorine adducted ions were detected in four compounds. The separation of four antibiotics was investigated with an HPLC column to apply this technique to the actual analysis. The capability was equal as in the flow injection method and it found that this technique, i.e. APCI-MS with bromoform could be applicable in the separation analysis.

Thermodynamic study and separation mechanism of diltiazem optical isomers in packed-column supercritical fluid chromatography

Abstract Cellulose tris(4-chlorophenylcarbamate) coated on silica was used as a chiral stationary phase for the separation of diltiazem (a Ca-channel blocker) optical isomers in packed-column supercritical fluid chromatography. The effect of temperature on the separation of the cis- and trans-enantiomers was studied in detail. The Van’t Hoff plots for the retention were found to be curves, while those for the selectivity were found to be linear. The chiral separation of cis-enantiomers was improved with a decrease in temperature, whereas that of trans-enantiomers was improved with an increase in temperature. To obtain a better understanding of the difference in the separations of cis- and trans-enantiomers, the temperature dependence of enantioselectivities was studied to determine the thermodynamic parameters ΔΔH°, ΔΔS°, and Tiso. The thermodynamic parameters revealed that the separation of trans-enantiomers was entropy-controlled in the range of temperature examined, whereas enthalpy-controlled separation was observed for cis-enantiomers. The separations of both cis- and trans-enantiomers, however, were enthalpy-controlled in normal-phase HPLC. The separations of the related compounds, 3-hydroxy isomers, were compared with those of diltiazem isomers. In addition, the differences in separation mechanisms between cis- and trans-enantiomers of diltiazem optical isomers are discussed by means of three-dimensional structures.

Chiral resolution of four optical isomers of diltiazem hydrochloride on Chiralcel columns by packed-column supercritical fluid chromatography

The optical isomers of diltiazem hydrochloride Ca-channel blocker were separated by packed-column sub- and/or supercritical fluid chromatography (p-SubFC and/or p-SFC) on a column of modified cellulose coated onto silica, using a mixture of carbon dioxide with a polar modifier and additive. The effect of parameters (Chiralcel columns, modifiers, additive, pressure and temperature) was investigated systematically, and the interactions between the diltiazem optical isomers and chiral stationary phase were discussed. Four optical isomers of diltiazem hydrochloride were achieved with baseline resolution on the Chiralcel OD column within 8 min. To determine three optical impurities in diltiazem hydrochloride, the precision, accuracy, linearity and detection limit were investigated, and the results were sufficiently acceptable. In addition, the resolutions in p-SFC were compared with those in high-performance liquid chromatography.

Formation of three-membered rings from γ-lodoketones and γ-lodoesters via 1,3-elimination

γ-Iodoketones, prepared by ene–halogenocyclization of α-haloketones with Pd(PPh3)4, on treatment with diazabicyclo[5.4.0]undec-7-ene afford three-membered ring compounds in good yield via syn-1,3-elimination, presumably via W-shaped transition states.

Application of the remote photocyclization with a pair system of phthalimide and methylthio groups: A photochemical synthesis of macrolide models

Abstract Based on the regioselective remote photocyclization of a pair system consisting of a phthalimide group and a terminal sulfide group in their side chain, a variety of azathiacyclic compounds containing 9- to 27-membered rings were synthesized.

Hydroximate as a synthetically useful functional group: A novel synthesis of lactones using hydroximates as a tether

Abstract Hydroximate has proved to be a potential functional group by realizing the radical cyclization of the dienes connected with the hydroximates 4 and 10 followed by conversion of the resulting cyclic hydroximates 5, 6, 11 , and 12 to lactones 13 and 14 .

Highly selective iodine-induced lactam formation from γ,δ-unsaturated thioimidates. New entry to functionalized γ-lactams

Iodine-induced lactam formation from γ,δ-unsaturated thioimidates proceeds regio- and stereo-selectively, providing highly functionalized γ-lactams.

Racemic syntheses of agelasimine-A and agelasimine-B, bicyclic diterpenoids from the marine sponge Agelas mauritiana

Abstract The first racemic syntheses of agelasimines-A and -B, adenine-related bicyclic diterpenoids from the marine sponge Agelas mauritiana, have been accomplished by means of routes through the diol 10 as a key intermediate for their common diterpene portion. As a result, their structures and relative stereochemistries have been unequivocally established to be those represented by formulas (±)-1a and (±)-2a, respectively.