PHOTOPHYSICS AND IONIC PHOTODISSOCIATION OF POLYESTERS WITH PENDANT 1-PYRENYL GROUPS IN SOLUTION

Primary photoprocesses of polyesters with pendant pyrenyl groups in solution were studied by means of nanosecond laser flash photolysis method. The intrapolymer process of the S_l S_l annihilation was observed. Intense laser excitation brings about dense population of several fluorescent states in a polymer chain, and their mutual interaction leads to efficient deactivation. This process is confirmed by excitation intensity dependence of fluorescence spectra and fluorescence intensity. It was also confirmed that the T-T absorption intensity decreases as the degree of polymerization increases. This low formation yield of the triplet state in the polyesters is ascribed mainly to the above S_l S_l interaction. In addition the polymer effect on the ionic photodissociation yield of the polyester-electron acceptor was investigated. The yield decreases as the degree of polymerization increases. This effect is due to slow solvation processes, which may be due to low micropolarity and high microviscosily around the polymer chain.     

Development of a catalytic electron transfer system mediated by transition metal ate complexes: applicability and tunability of electron-releasing potential for organic transformations

We have developed a catalytic electron transfer (ET) system composed of a transition metal ate complex (Me3M(II)Li; M = Co(II), Mn(II), Fe(II)) and magnesium. This system (catalytic Me3M(II)Li/Mg) turned out to be effective for various ET reactions, such as the desulfonylation of N-phenylsulfonyl amides, and others (the chemoselective cleavage of O-allyl groups, the reduction of nitro groups, the partial reduction of diketones, and the reductive coupling of diphenyliodonium salt). The ET ability of this system can be tuned by changing the ligands of the ate complexes. This tunability was experimentally and electrochemically demonstrated: alkoxy-ligated and dianion-type ET ate complexes showed attenuated and enhanced reducing abilities, respectively. The modification of the ET abilities was evaluated by means of electrochemical measurements and chemical reactions. These results provide a basis for the design of various tailor-made ET ate complexes.     

A note on maximality of analytic crossed products

Let G be a compact abelian group with the totally ordered dual group which admits the positive semigroup . Let N be a von Neumann algebra and be an automorphism group of on N. We denote to the analytic crossed product determined by N and α. We show that if is a maximal σ-weakly closed subalgebra of , then induces an archimedean order in .     

Protonation Switching to the Least‐Basic Heteroatom of Carbamate through Cationic Hydrogen Bonding Promotes the Formation of Isocyanate Cations

We found that phenethylcarbamates that bear ortho‐salicylate as an ether group (carbamoyl salicylates) dramatically accelerate O?C bond dissociation in strong acid to facilitate generation of isocyanate cation (N‐protonated isocyanates), which undergo subsequent intramolecular aromatic electrophilic cyclization to give dihydroisoquinolones. To generate isocyanate cations from carbamates in acidic media as electrophiles for aromatic substitution, protonation at the ether oxygen, the least basic heteroatom, is essential to promote C?O bond cleavage. However, the carbonyl oxygen of carbamates, the most basic site, is protonated exclusively in strong acids. We found that the protonation site can be shifted to an alternative basic atom by linking methyl salicylate to the ether oxygen of carbamate. The methyl ester oxygen ortho to the phenolic (ether) oxygen of salicylate is as basic as the carbamate carbonyl oxygen, and we found that monoprotonation at the methyl ester oxygen in strong acid resulted in the formation of an intramolecular cationic hydrogen bond (>C?O⁺?H???O<) with the phenolic ether oxygen. This facilitates O?C bond dissociation of phenethylcarbamates, thereby promoting isocyanate cation formation. In contrast, superacid‐mediated diprotonation at the methyl ester oxygen of the salicylate and the carbonyl oxygen of the carbamate afforded a rather stable dication, which did not readily undergo C?O bond dissociation. This is an unprecedented and unknown case in which the monocation has greater reactivity than the dication.     

Stereoselectivity of superacid-catalyzed Pictet-Spengler cyclization reactions

[reaction: see text] High stereoselectivities were found in a wide range of superacid-catalyzed Pictet-Spengler cyclization reactions. Particularly in the cases of 2-alkyl-N-benzylidene-2-phenethylamines, an enhanced stereoselectivity was observed under the superacid conditions as compared with the corresponding weak acid (TFA)-catalyzed (monocationic) cyclization reaction of the N-benzylidene-2-(3',4'-dimethoxy)phenethylamines that bear electron-donating groups on the cyclizing aromatic ring. The computational study also supported the energetic favorability of the cyclization of the N,N-diprotonated imine and revealed a significantly early transition-state structure.     

Heteronuclear diatomic force constants clarified through perturbation theory II

A simple relationship between the heteronuclear diatomic force constant (K(AB)) and the homonuclear diatomic force constants (K(AA), K(BB)), which was proposed in a previous report, has been improved through the second-order perturbation theory as K(AB) = zeta3(K(AA) x K(BB))(1/2); zeta = (R(AA) x R(BB))(1/2)/R(AB) where zeta denotes the correction factor in which R(AB), R(AA), and R(BB) are the equilibrium internuclear distances of diatomic molecules AB, AA, and BB, respectively. To test the above expression, a large number of heteronuclear diatomic force constants have been calculated and compared with those obtained from normal coordinate analyses as well as ab initio quantum mechanical methods (Gaussian 98W). We have found that the above modified expression better reproduces the force constants of most heteronuclear diatomic molecules than the previous expression. It is therefore expected that the expression may also be applied to the prediction of stretching force constants between heteronuclear diatomics in various polyatomic molecules.     

Force constants of angle deformation in triatomic molecules

An expression for the angle deformation force constant of a polyatomic molecule has been derived on the basis of electrostatic theorem. By testing this expression with a number of triatomic molecules, it has been shown that the expression is useful for predicting the force constant of angle deformation in triatomic molecules.     

Retro-Diels-Alder reaction of 4H-1,2-benzoxazines to generate o-quinone methides: involvement of highly polarized transition states

Here, we describe mechanistic studies of the retro-Diels-Alder reaction of 4H-1,2-benzoxazines bearing various substituents on the benzene ring. 4H-1,2-Benzoxazines are very simple, but quite new, heterocyclic compounds that afford substituted o-quinone methides (o-QMs) through retro-Diels-Alder reaction under mild thermal conditions. The resultant o-QMs undergo Diels-Alder reaction in situ with dienophiles to give phenol and chroman derivatives. The mechanism of the generation of o-QMs has been little studied. Our experimental and density functional theory (DFT) studies have yielded the following results. (1) The generation of o-QMs, i.e., the retro-hetero-Diels-Alder reaction of 4H-1,2-benzoxazines, is rate determining, rather than the subsequent Diels-Alder reaction of the resultant o-QM with dienophiles. (2) The reaction rate is strongly influenced by the electronic features of substituents and the polarity of the solvent. The reaction proceeds faster in a polar solvent such as dimethyl sulfoxide, probably because of stabilization of the electronically polarized TS structure. (3) The reactions show characteristic positional effects of substitution on the benzene ring. While an electron-withdrawing group such as CF3 at C5, C6, or C7 positions decelerates the reaction, the same substituent at C8 accelerates the reaction, compared with the reaction of unsubstituted 4H-1,2-benzoxazine. In particular, substitution at C5 significantly decelerates the reaction as compared with the unsubstituted case. This is due to the difference in the inductive effect of CF3 at the different positions. Similar positional effects occur with a halogen (Cl) and a nitro group. All these data support the involvement of polarized TS structures, in which the O-N bond cleavage precedes the C-C bond cleavage.     

Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors

Lung cancer has a high prevalence, with a growing number of new cases and mortality every year. Furthermore, the survival rate of patients with non-small-cell lung carcinoma (NSCLC) is still quite low in the majority of cases. Despite the use of conventional therapy such as tyrosine kinase inhibitor for Epidermal Growth Factor Receptor (EGFR), which is highly expressed in most NSCLC cases, there was still no substantial improvement in patient survival. This is due to the drug’s ineffectiveness and high rate of resistance among individuals with mutant EGFR. Therefore, the development of new inhibitors is urgently needed. Understanding the EGFR structure, including its kinase domain and other parts of the protein, and its activation mechanism can accelerate the discovery of novel compounds targeting this protein. This study described the structure of the extracellular, transmembrane, and intracellular domains of EGFR. This was carried out along with identifying the binding pose of commercially available inhibitors in the ATP-binding and allosteric sites, thereby clarifying the research gaps that can be filled. The binding mechanism of inhibitors that have been used clinically was also explained, thereby aiding the structure-based development of new drugs.     

Exploiting a C–N Bond Forming Cytochrome P450 Monooxygenase for C–S Bond Formation

C–S bond formation reactions are widely distributed in the biosynthesis of biologically active molecules, and thus have received much attention over the past decades. Herein, we report intramolecular C–S bond formation by a P450 monooxygenase, TleB, which normally catalyzes a C?N bond formation in teleocidin biosynthesis. Based on the proposed reaction mechanism of TleB, a thiol‐substituted substrate analogue was synthesized and tested in the enzyme reaction, which afforded the unprecedented sulfur‐containing thio‐indolactam V, in addition to an unusual indole‐fused 6/5/8‐tricyclic product whose structure was determined by the crystalline sponge method. Interestingly, conformational analysis revealed that the SOFA conformation is stable in thio‐indolactam V, in sharp contrast to the major TWIST form in indolactam V, resulting in differences in their biological activities.