Nobuya Nagashima

Highly diastereoselective aldol reaction of fluoroalkyl aryl ketones with methyl isocyanoacetate catalyzed by silver(I)/triethylamine

Abstract Transition metal-catalyzed aldol reaction of aryl fluoroalkyl ketones with methyl isocyanoacetate was found to proceed with high diastereoselectivity that is in sharp contrast to the very poor diastereoselectivity in the similar reaction of nonfluorinated ketones. The superiority of AgClO4/NEt3 as a homogeneous catalyst (1 mol %) for these reactions was disclosed.

Effects of additives on the growth of L-glutamic acid crystals (β-form)

Abstract To elucidate the mechanism of polymorph-selective crystallization of L-glutamic acid (L-Glu) crystals by the additives, the effects of various L-amino acids, carboxylic acids, and a di-peptide, γ-L-glutamyl-L-glutamic acid (γ-Glu-Glu) on the growth of the {1 0 1 }, {0 1 0}, and {0 0 1}, three dominant faces of the β-form of L-Glu crystals have been investigated experimentally and structurally. γ-Glu-Glu and L-phenylalanine (L-Phe) showed nearly the same strong inhibitory effects on the three faces of the β-form in contrast to their different behavior on the two dominant faces of the α-form of L-Glu. These phenomena were explained in terms of the characteristics of the hydrogen bonds of each face and it was found that the β-form has less discriminating capacity than the α-form for the recognition of the molecules. Finally, the cause of the polymorph-selective crystallization by the additives in the L-Glu is attributed mainly to the difference in the inhibitory effects of the additives on the two dominant faces of the α-form.

Studies of hydration by broad-line pulsed NMR

Abstract Water molecules are distributed among a great variety of materials: organic and inorganic crystals, gels and sols of natural products with mineralogical, botanical, and zoological origins, as well as industrial products. The water molecules in living cells and their constituents are essential, not only as a solvent or a supporting medium, but also as an indispensable component. One of the effective methods of characterizing such water molecules is a proton magnetic resonance measurement. Kuntz et al. [l] once observed that frozen protein and nucleic acid solutions at −35°C show relatively narrow (100 milligauss) proton magnetic resonance signals. They showed that this signaI is assignable to water of hydration. Thus, at this temperature (−35°C), the regular solvent water is frozen, and practically all the protons in the macromolecules are immobilized, so that only the water of hydration is sufficiently mobile in the given system to reduce the dipolar broadening and to give a signal. On the basis ...

The effects of additives on the crystal habit of monosodium L-glutamate monohydrate

The effects of various amino acids and organic acids on the habit of MSG crystals have been investigated. The addition of L-alanine (L-Ala) and L-lysine (L-Lys) made the MSG crystals short and thick, but D-glutamic acid (D-Glu), γ-amino butylic acid (γ-ABA) and L-pyrrolidone carboxylic acid (L-PCA) made the crystals long and thin. HPLC analysis of the end and the side faces of the MSG crystals grown with the additives revealed that the concentrations of L-Lys and L-Ala were higher at the end faces than at the side faces; but those of D-Glu, γ-ABA and L-PCA were higher at the side faces than at the end faces. The facts indicate that habit modifications of the MSG crystals, brought about in the presence of these additives, are due to stereo-selective adsorption of the additives on the crystal faces. Finally, the cause leading to the differences in adsorption of the additives on the crystal faces of MSG is discussed in relation to the stacking density of L-Glu molecules and Na ions on each face using the results of the X-ray structure analysis.

Effects of L-glutamyl peptides on the growth of L-glutamic acid crystals (α-form)

Abstract The effects of five γ-L-glutamyl peptides, two α-L-glutamyl peptides, and L-phenylalanine (L-Phe) on the growth of {111} and {001} faces of the α-form of L-glutaminic acid (L-Glu) crystals were investigated. All the γ-L-glutamyl and α-L-glutamyl peptides and L-Phe had inhibitory effects on the growth of the {111} face, but γ-Glu-Glu, γ-Glu-ϵ-Lys, and Glu-Glu suppressed not only the {111} faces but also the {001} faces. Thus, the distribution of additives on the {111} and {001} faces of L-Glu crystals was analyzed. Results showed that the {001} face of L-Glu crystals had higher concentrations of γ-Glu-Glu, γ-Glu-ϵ-Lys, and Glu-Glu than other peptides. The effect of γ-Glu-Glu on inducing the β-form is considered to be closely related to its specific character of inhibiting the growth of both the {111} and {001} faces of the α-form. These phenomena are discussed on the basis of the crystal structure.

In-situ observation of the concentration gradient layer around a growing crystal of leucine complex

Abstract The concentration gradient layer around a growing crystal of L-leucine complex was observed using a Michelson interferometer. From the interferograms and growth-rate measurements in the stagnant solution, we could estimate the growth mode and the diffusion coefficient of the complex of L-leucine (L-leu) and 3,4-dimethylbenzenesulfonic acid (o-DMBS). Growth rate versus surface supersaturation could be shown as R ( σ ) = 2.35 × 10 −7 σ 1.65 , and the diffusion coefficient was estimated to be 7.2 × 10 −10 m 2 /s. The estimated Stokes radius coincided with the size of each molecule of L-leu and o-DMBS.

Characterization of organic crystal products

The characterization of organic crystal products, based on internal structure using powder X-ray diffraction, was investigated with two substances. In the case of L-histidine α-ketoisocaproic acid complex ethanolate, the de-ethanolation rate increases when the crystal shows stronger intensities of (002) reflection. The difference of the intensities of the (002) reflection was found to be caused by the internal structure (i.e. degrees of crystallinity and preferred orientation). The layer structure of L-histidine α-ketoisocaproic acid complex ethanolate [1] could explain the crystal structure having the tendency to take a structure with preferred orientation. In the case of the α-form of L-aspartic acid, the degree of preferred orientation varies according to the crystallizing rates. Different crystal habits are noted among these samples. As a result of the simulation of a powder X-ray diffraction pattern from the crystal structure, the difference of the degree of preferred orientation is shown to reflect the global anisotropic displacement of molecules.

Structure of a DNA octamer, d(CCTTAAGG)2 obtained by restrained molecular dynamics based on Raman and NMR data

Abstract The structure of a DNA octamer, d(CCTTAAGG) 2 , was investigated in aqueous solution by Raman and NMR spectroscopies. Based on proton—proton distances and torsion angles obtained by NOESY and Raman experiments, respectively, restrained molecular dynamics calculations were carried out. These methods are complementary and allow an optimum structure, which is independent of the initial structures used in the calculations, to be derived. By combining both sets of data, some ambiguities in the potential energy calculations and in the estimation of the distances from NOE experiments are removed. The reconstructed structure indicates that the octamer bends towards the major groove at the TA step, showing a relatively large dynamic motion at this junction. This bending is caused by hydrophobic interaction between the methyl groups of the four thymidine residues located in the centre of the duplex.

Desolvation of L-Histidine and cr-Ketoisocaproic Acid Complex from Ethanolate Crystals Under Humidified Conditions and Influence of Crystallinity on Its Desolvation.

エタノール-水混合溶媒中での晶析によりエタノール和物結晶を形成する, ヒスチジン・ケトイソカプロン酸塩について, 工業的な製法開発を前提とした脱エタノール法の検討を行った.ヒスチジン・ケトイソカプロン酸塩のエタノール和物結晶は, 高湿度条件下 (例えば313K, 60%相対湿度) で, 結晶転移を伴って速やかにエタノールが離脱し, 無溶媒和型の結晶となった.なお, エタノール和物結晶において, 粉末X線回折の2θ= 9.0° (CuKα) のピーク高さが比較的高い場合には, 高湿度条件下において結晶転移終了と同時に脱エタノールが完了したが, このピークが低い場合には転移終了後も1wt%程度のエタノールが残留し, 以降緩慢な低下傾向を示した.脱エタノール性に優れる, 結晶性の高い結晶を再現性良く得るためには, 晶析時にエタノール添加によって大過飽和を急激に生成するよりも, 冷却操作によって過飽和生成速度を緩やかに制御することがより効果的であることを見いだした.