Tetsuro Shimo

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).

Solid-State Photocycloaddition Reactions of Tri-2-Pyrones with Benzophenone

Solid-state photocycloaddition reactions between tri-2-pyrones (1a,1b) with benzophenone (2) gave the corresponding oxetane derivatives (3a:3a′=1:1 and 3b:3b′=1:1, 1:2 adducts) with high site- and regioselectivity across the C5-C6 , C5′-C6′ and C5′′-C6′′ double bonds in 1 via the triplet excited state of 2. The site- and regioselectivities were explained by MO calculations. The hydrogen-bonding interaction between 2 and 1a, 1b and the triplet reaction mechanism were also explained by the IR analyses and the quenching experiments, respectively.

Solid-State Photocycloaddition Reactions between Di-2-Pyrones Tethered by Arylalkyl Chain and Benzophenones

Solid-state photocycloaddition reactions between di-2-pyrones (1a-d) with benzophenone (2a) gave the corresponding oxetane derivatives (3a-d; 1:2 adducts) with high site- and regioselectivity across the C5-C6 and C5′-C6′ double bonds in 1 via the triplet excited state of 2a. The reactions were inferred by MO methods to be initiated by electrostatic interaction between the C6 position of 1a-d and the carbonyl oxygen of 2a at their ground states, and the solid-state interaction may be enhanced by electron density at carbonyl oxygen of the triplet 2a. The transition state (TS) analysis of the [2+2] cycloaddition reactions also suggested some triplet complex, and the high regioselectivity. The hydrogen-bonding interaction between 2a and 1a-d and the triplet reaction mechanism were also explained by the IR analyses and the quenching experiments, respectively.