Photodynamic inactivation (PDI) has received considerable attention as a methodology leading to the medical applications such as photodynamic therapy (PDT) for tumor cells. Porphyrin derivatives are attractive singlet-oxygen sensitizers for PDT because of their strong absorption band in the visible-light region. In general, free-base porphyrins comprise four Q-bands regions near 515, 550, 590, and 645 nm; these band regions have wider and longer wavelengths in comparison with that of the Q-bands of metalloporphyrins (560-610 nm). Therefore, most sensitizers for PDT are based on free-base porphyrins or chlorins (i.e. photofrin and laserphyrin). We have been interested in the use of phosphorus porphyrins (P-porphyrins) as photosensitizer. It is advantageous in P-porphyrins that water-solubilization is easily achieved through the modification of the axial ligands and the presence of these axial ligands also prevents the formation of porphyrin-ring aggregates. The aggregation may lower the water solubility of the porphyrins and retard the incorporation of the porphyrins into the target cell. This review is focused on the phosphorus porphyrin (1 and 2) modified by axial ligands such as -(CH₂CH₂O)_m(CH₂)_nH and alkylpyridinium (APy) group, respectively. The PDI activities of 1 and 2 for Saccharomyces cerevisiae, Escherichia coli, and a human biliary cancer cell line (NOZ) have been evaluated using the half-life (T_1/2 in min) of bacteria and the minimum effective concentrations ([P]) of the sensitizers. As the results, the [P] values for the PDI of S. cerevisiae was optimized to be 5 nM for 1e (m=2, n=6) and 1f (m=1, n=6). In the case of the PDI of NOZ cell, the IC₅₀ for 1e was determined to be 37.6 nM which were one hundredth the IC₅₀ (7.57 µM) for mono-l-aspartyl chlorin e6 (laserphyrin). The [P] values for S. cerevisiae were optimized to be 40 nM at 2h (alkyl=hexyl). In the case of the PDI of E. coli using 2, the PDI activity depends on the alkyl chain length of Apy. The [P] value for E. coli was optimized to be 250 nM (2b, alkyl=ethyl). Thus the P-porphyrins are applicable to the PDI of bacteria and cancer cells in low concentrations.

Amide C-N bond in 2,6-di-tert-butylanilides has a high rotational barrier and the individual amide rotational isomers can be isolated at ambient temperature. These anilides have been reported by Chupp et al. in 1967, but no systematic study with anilide substrates other than α-haloacetoanilides, or the stereoselective synthesis of anilide rotamers have been reported. In addition, the structural properties of these anilides have not been investigated in detail. We succeeded in the highly selective stereodivergent synthesis of Z- and E-rotamers of various N-allyl-2,4,6-tri-tert-butylanilides through Pd(0) and Pd(II) catalyzed N-allylation of O-allyl-N-(2,4,6-tri-tert-butylphenyl)imidates. Moreover, the relative thermodynamic stabilities of the obtained anilide rotamers were clarified. Specific reactivity of 2,4,6-tri-tert-butylanilide derivatives was also found. For examples, in intramolecular Diels-Alder reaction of N-ally 2-furoyl amides, 2,4,6-tri-tert-butylphenyl group on the nitrogen atom remarkably accelerated the reaction. Although the reaction of ordinal anilide anion with alkyl halide gives N-alkylation product, the alkylation with 2,4,6-tri-tert-butylanilide anion preferentially proceeded on the oxygen atom to give O-alkyl imidate. O-Benzyl imidate, which was obtained by the reaction with benzyl bromide, was used as bezylation reagent of alcohols and carboxylic acids. In contrast to rotational rigidity of 2,4,6-tri-tert-butylanilide, in the anilide enolates, interconversion between the rotamers readily occurs at ambient temperature, and their reaction with electrophiles gave rotamer mixtures of the products in a ratio that depends on the reactivity of the electrophiles. Furthermore, as an application of this isomerization reaction, switching between the anilide rotamers was achieved.

Functional group having two adjacent heteroatoms exhibits unique characteristic features such as relatively higher nucleophilicity. In this account, transition metal-catalyzed intramolecular nucleophilic addition reaction of imines and amides bearing the alkoxy group on the nitrogen atom onto alkyne for the synthesis of a variety of heterocycles was described. The cyclization of N-alkoxyalkynylimines and subsequent rearrangement of the substituent on the oxygen atom provided trisubstituted isoxazoles in a highly atom-economical manner. In addition, gold-catalyzed cascade reaction of N-allyoxyalkynylimines involving cyclization and subsequent [3+2]/retro-[3+2]/[3+2]cycloaddition reactions via generation of N-allyloxyazomethine ylide gave fused and bridged isoxazolidines. Reagent-controlled regiodivergent cyclization of Weireb amide, prepared from o-alkynyl benzoic acid, furnished isobenzofuranone and isoquinolinoes. Sequential reaction involving cyclization and rearrangement of N-allyloxypropiolamide for the preparation of 3-hydroxyisoxazoles also described.

Activation of boronic acids or related compounds by chiral organocatalysts has emerged as efficient methods for construction of optically active organic molecules. Although several effective organocatalysts such as 3,3’-disubstituted binaphthols or thiourea derivatives have been developed to promote 1,2- or 1,4-addition to (conjugated) carbonyl compounds or imines, such reports are still limited. It is known that α-hydroxycarboxylic acids smoothly react with boronic acids to generate dioxaborolanones having high Lewis acidity. We hypothesized that the dioxaborolanone formation would prompt the activation of B-C bonds and formation of new C-C bond, and found that O-monoacylated tartaric acids (MAT) effectively catalyze 1,4-additions of boronic acids or bis(neopentyl glycolato)diboron to α,β-unsaturated ketones (enones). This article describes development and application of MAT catalysts.

In this article, we have summarized our recent efforts to use chiral bidentate phosphoramidites for asymmetric hydroarylation. Asymmetric intramolecular hydroarylation of α-ketoamides gave various types of optically active 3-substituted 3-hydroxy-2-oxindoles in high yields with complete regioselectivity and high enantioselectivities (84—98% ee). This asymmetric hydroarylation was realized by the use of the cationic iridium complex [Ir(cod)₂](BAr^F₄) and the chiral O-linked bidentate phosphoramidite (R,R)-Me-BIPAM. A catalytic cycle involving C-H bond cleavage to give an Ar-[Ir]⁺ intermediate, insertion of a carbonyl group into the aryl-iridium bond, giving iridium alkoxide, and finally reductive elimination to reproduce active [Ir]⁺ species was proposed. The mechanistic insight for the iridium hydride species indicated that the C-H bond cleavage is caused in a reversible manner. Because the kinetic isotope effect was determined that k_H/k_D was 1.85, the C-H bond cleavage step was not included in the turnover-limiting step. In addition, Hammett studies of substrates (ρ=−0.99) demonstrated that electron-donating groups at the para position to the reactive C-H bond accelerate the reaction rate. This linear relationship obtained in the Hammett plot indicated that the nucleophilicity of the aryl-iridium intermediate is an important factor in this reaction. All of the data indicated that carbonyl insertion into aryl-iridium was included in the turnover-limiting step of the catalytic cycle. Meanwhile, highly enantioselective cationic iridium-catalyzed hydroarylation of bicycloalkenes, by carbonyl-directed C-H bond cleavage, was accomplished using a newly synthesized sulfur-linked bis(phosphoramidite) ligand (S-Me-BIPAM). The reaction provided alkylated acetophenone or benzamide derivatives in moderate to excellent yields and good to excellent enantioselectivities. Notably, the hydroarylation reaction of 2-norbornene with N,N-dialkylbenzamide proceeded with excellent enantioselectivity (up to 99% ee) and high selectivity for the mono-ortho-alkylation product. Deuterium incorporation experiments indicated that C-H bond cleavage occurs in a non-reversible manner prior to the alkene insertion. A kinetic isotope effect (KIE) of 2.08 indicated that the turnover-limiting step included the C-H bond cleavage step.

Developing new methodology of polypeptide synthesis has afforded well-defined polymer-polypeptide hybrid materials for various bio-applications. One of the most efficient routes is a ring-opening polymerization of α-amino acid N-carboxyanhydrides (NCAs), permitting the preparation of well-defined structures in terms of the molecular weight and terminal structures of the polypeptide. However, highly toxic phosgene derivatives are usually required for the synthesis of NCAs, and the susceptive nature of NCAs to moisture and heating are major obstacles for its practical and industrial-scale use. This article describes our recent works on phosgene-free synthesis of polypeptide by polycondensation of N-aryloxycarbonyl α-amino acids, where these activated urethane derivatives gives directly corresponding polypeptides by forming NCAs in situ and the polymerization with the elimination of phenol and CO₂. Due to the ease of handling and the simple procedure, this methodology for making a functionalized polypeptide is more useful and valuable than the conventional ring-opening polymerization of NCAs, and expected to be applied to designing the biocompatible and biodegradable biomaterials.

Acceptorless dehydrogenation (AD) reaction of alcohols are excellent atom-economical approach to yield carbonyl compounds without stoichiometric oxidants. Furthermore the liberated hydrogen can also be used in situ for hydrogenation of the unsaturated intermediates generated by the condensation reaction. Although the aforementioned reactions are based on precious novel-metal catalysts, nowadays several efficient catalysts composed of earth-abundant base metals (Mn, Fe, Co, Ni) have been developed. This review focuses on recent reports about manganese catalyzed C-N bond formation in combination with amines and methanol as a C1 source.

Nuphar alkaloids are a small family of bioactive terpene alkaloids with unusual bis(spirothiolane)structure. This review focused on dimeric Nuphar thioalkaloids containing hemiaminal moieties. Total syntheses of these alkaloids by Wu and Zakarian and bioorganic study by Shenvi are described.

This review highlights recent progress of metal-graphene conjugates which catalyze sophisticated conversion reactions by horseradish peroxidase(HRP). Hemin supported by graphene accelerates the oxidation of pyrogallol to purpurogallin with high catalytic activity. Copper(II) ions on graphene oxide promote the oxidation of dopamine to aminochrome. In these reactions, carbon nanomaterials are necessary and notably activate these metal ions.