Kenichi Somekawa

9-Hydroxymethylcyclopropylidenemethylenyladenine: The design, facile synthesis, isomer separation and anti-HIV-1 activities

Abstract 9-Hydroxymethylcyclopropylidenemethylenyladenine was designed based on the analysis of the structure-activity relationship and synthesized by coupling reaction of a vicinal dibromocyclopropane derivative with adenine. The cis/trans isomers and an enantiomer of the cis-isomer of the cyclic α, β-unsaturated nucleosides derived by reduction were separated by reverse phase HPLC and chiral HPLC, respectively. The cis-isomer was effective against HIV-1 and the (−)cis-isomer was highly effective with EC50 13 μM.

Remarkable interaction effects of molecular packing on site- and stereoselectivity in photocycloaddition of 2-pyrones with maleimide in the solid state

Abstract Solid-state photoirradiation of 1:1 complex crystals of 4-[ω-(2-furyl)alkyloxy]-6-methyl-2-pyrones 1b, 1c or 4-(ω-arylalkyloxy)-6-methyl-2-pyrones 1d–j with maleimide 2 gave [2+2]cycloadducts 3b–f, 3i, 3j with exclusive stereoselectivity. The high reaction selectivity was confirmed by X-ray structure analyses and MO method of the complex crystals, which were composed of two sets of a 1:1 complex between 1 and 2, arising from an CH–π interaction between 2 and the aromatic rings of 1, and/or π–π stacking between the aromatic rings in addition to four kinds of hydrogen bonding between the ground state 2-pyrone moieties and 2.

Reactions of methylenecyclopropanes with a diethylzinc-bromoform system, and the utilization for synthesis of a novel cyclopropylidene-nucleoside

Abstract The reactions of substituted methylenecyclopropane with diethylzinc-bromoform gave bromospiro[2.2]pentane derivatives, bromoform-addition compounds, an oxabicyclo-compound and adjacent dibromo-compound, and the last product was derived to a novel α,β-unsaturated nucloside.

SUBSTITUENT EFFECTS ON THE REGIOCHEMISTRY OF ENONE-ALKENE 2+2-PHOTOCYCLOADDITIONS. EXPERIMENTAL RESULTS AND FMO ANALYSIS

Abstract The regiochemical selectivities (i. e., head-to-head (hh) and head-to-tail (ht)) of 2+2-photocycloaddition reactions of cyclic α,β-unsaturated carbonyl compounds (1, 2, 5, 8, 9) with substituted alkenes have been determined experimentally. The observed preferences, associated with a two-step mechanism via biradical intermediates for addition of ground state alkenes to triplet enones. were analyzed by use of frontier molecular orbital (FMO) methods using molecular orbital energies and coefficients of corresponding species calculated by the PM3-CI method. Regiochemical selectivities for the two-step 2+2-photocycloadditions were then analyzed in terms of two-center HSOMO-LUMO and LSOMO-HOMO interaction factors Srl corresponding to bonding between the enone triplet and alkene leading to formation of biradical precursors of the respective head-to-head and head-to-tail adducts. In addition, intramolecular interaction factors Sr2, corresponding to cyclization of the biradical intermediates were also determined. Good correlations were seen between the calculated interaction factor differences(e.g. Srl3β-Srl2β) and logarithims of the experimentally determined adduct ratios (e.g. log hh/ht). This observation suggests that the excited state 2+2-cycloaddition regioselectivities are mainly determined in the initial biradical producing step of this process but that they can be altered by partitioning of the biradical intermediates to product vs. ground state reactants.

X-Ray and MO analysis of highly stereoselective solid-state photocycloadditions of 2-pyrones with maleimide

Abstract Photoirradiations of grinding mixtures of 4-(ω-arylalkyloxy)-6-methyl-2-pyrones 1i–1o and maleimide 2 in the solid state quantitatively gave only a [2+2] cycloadduct 3j with high stereoselectivity. The 1:1 complex crystals 1j · 2 , and 1a · 2 , 1b · 2 , 1c · 2 , 1d · 2 , 1g · 2 , 1h · 2 from another 2-pyrones with 2 , were characterized by powder X-ray diffraction technique. The crystal formation was remarkably affected by polar and bulky nature of the substituents at the aryl groups. Four kinds of hydrogen bondings by two ground state species for the crystals were quantitatively estimated, and the photoreaction mechanism was analyzed to proceed via some interactions of the singlet excited state of 1 with ground state of 2 by MO transition state calculation.

Efficient 2-amino-2-thiazolin-4-ones or 2-iminothiazolidin-4-ones formation from thioureas and maleimides under solvent-free conditions

A facile method for the construction of 2-thiazolin-4-one or thiazolidin-4-one structure is described. Condensation reactions of thiourea (la) and maleimides (2) under solvent-free conditions gave 2-amino-2-thiazolin-4-ones (3) via Michael-type reaction, while similar reactions of N-substituted thioureas (1b-d) with 2 afforded 2-iminothiazolidin-4-ones (4). Since the solvent-free reactions of 1 with 2a afforded 3 in good yields, the synthetic method was found to be effective from the viewpoint of green chemistry.

Efficient Photochemical Oxetane Formation from 2-Pyrones and Benzophenones in the Solid State

Solid-state photocycloaddition reactions of 2-pyrones (1, 4) with benzophenone derivatives (2a-c, f) afforded highly site- and regioselective oxetanes (3a, 3b, 3c, 3f, 5a, 5b, 5c, 5f) across the C5-C6 double bond in 1 or 4 via the triplet excited state of 2. The site- and regioselectivities were explained by MO calculations.

One-pot synthesis of macrocyclic dioxatetralactones from the sequential inter- and intramolecular [2+2] photocycloaddition reactions

Sensitized photocycloaddition reactions of polymethylenedioxy-di-2-pyrones (1 - 3) with ethylene diacrylate (4a) afforded macrocyclic dioxatetralactones (6a - 8a) having sixteen- to eighteen-membered rings. Similar reaction of 1 with ethylene dimethacrylate (4b) afforded similar lactones (6b) and (9). The stereochemical features of 6a and 7a depending on the chain length elucidated by the X-Ray crystal analysis are figured by MOPAC conformational analysis of the reactants (1, 2 and 4a).

1H NMR spectra of 1-alkyl-1,2,3,4-tetrahydro-2-oxo-3-azocine-carboxylic acid derivatives and their analogues

1H NMR spectra of 1-alkyl-1,2,3,4-tetrahydro-2-oxo-3-azocinecarboxylates and -carbonitriles indicated that the geminal protons at the 1-α-position were located in noneqnivalent magnetic environments. The difference in the chemical shifts amounted to as much as 0.73 ppm in the case of methyl 1-ethyl-1,2,3,4-tetrahydro-2-oxo-3-azocinecarboxylate at 26°, and the free energy of activation for the coalescence was estimated to be larger than 23 kcalmol. The same type of nonequivalence and coalescence phenomena were also observed even with dimethyl protons at the 1-γ-position of 1-isobutyl-1,2,3,4-tetrahydro-2-oxo-3-azocinecarboxylate (ΔG≠c = 19 kcalmol). The situation was hardly affected by the reduction of the CC double bonds. The nonequivalence was not observed, however, if the substituent at the 3-position was absent. Therefore, these novel 1H NMR spectra of 1-alkyl protons in the title compounds were concluded to be due to strong coupling between the restricted rotation around N(1)—C(α) bond and inversion of the 2-oxoazocine ring which required high energy of activation.

Special articles on zeolite chemistry and technology. Synthesis of pure zeolites by dilute alkaline hydrothermal treatments of Shirasu.

シラスのアルカリ水熱処理でP型ゼオライトを晶出させた後に得られる炉液(P型源液)は, シリカ分が多く, アルミナと鉄分が非常に少ない。このP型濾液にアルミン酸ナトリウムを添加して鉄分を含まない高純度A型およびP型ゼオライトを合成した。その合成条件はA型でほ浴温100℃で, SiO2/Al203 モル比2付近であり, P型では120℃でその比の53付近と大きい条件であた。X型は単一相としては得られ難い。P型濾液からの各ゼオライトの生成過程を固相および液相の分析を行ない解析した。まず室温での組成調製および熟成過程で, 固体で加えたアルミン酸ナトリウムが液栢中のシリカと接触してSiO2/Al203モル比の小さいゲル状沈殿物を生じる。これが加熱により, ゼオライト核となり, 結晶化が起こったと推定された。したがってSiO2/Al203 モル比の小さいA型は常に初めに生成し, もっとも合成されやすいことになる。P型は耐アルカリ性が高いため, 3M程度のアルカリ条件下の高温域 (120℃) で得られたと判断される。合成したゼオライトの化学組成, 比表面積, 熱的変化, 水分吸着能も調べた。