Optical Activity and Optical Anisotropy in Photomechanical Crystals of Chiral Salicylidenephenylethylamines.

Introducing chirality into photomechanical crystals is beneficial for the diversification of mechanical motion. Measurement of the chiroptical and optical anisotropic properties of chiral crystals is indispensable for evaluating photomechanical crystals. The platelike crystals of S- and R-enantiomers of photochromic N-3,5-di-tert-butylsalicylidene-1-phenylethylamine in enol form (enol-(S)-1 and enol-(R)-1) caused bending motion with twisting upon ultraviolet (UV) light irradiation, due to shrinkage along the length and width directions of the irradiated surface, based on the optimized crystal structure of the photoisomerized trans-keto-(S)-1. By employing the generalized high-accuracy universal polarimeter (G-HAUP), optical anisotropic (linear birefringence, LB; linear dichroism, LD) as well as chiroptical (circular birefringence, CB; circular dichroism, CD) spectra of both the enantiomeric crystals on the (001) face were simultaneously measured before and under continuous UV irradiation. The LD peak was observed at 330 nm in the negative sign, derived from the π-π* transition of the intramolecularly hydrogen-bonded salicylidenimino moiety. The CD spectra of the S and R crystals revealed the negative and positive Cotton effect at 330 nm, respectively, and new peaks appeared at 460 nm under UV light irradiation due to photoisomerization to the S and R trans-keto isomers at around 10% conversion. The CB and CD spectra evaluated by the HAUP measurement were opposite to those measured in the hexane solution, as well as those simulated by quantum chemical calculation. The dissymmetry parameter, g, of the enol-(S)-1 crystal along the c axis (0.013) was approximately 10 times larger than the g values in the solution (0.0010) and by calculation (0.0016).

The Design, Synthesis, and Evaluation of 1,5,7-Trisubstituted-3-Pyridyl-Xanthones for Use as Insecticides Starting from Pyripyropene†A.

A readily accessible template of 1,5,7-trisubstituted-3-pyridyl-xanthones was designed starting from naturally occurring pyripyropene A for agrichemical development. Our originally developed Ag2 CO3 -mediated oxidative cyclization enabled ready access to the key scaffold, 1,5,7-trihydroxy-3-chloro-xanthone. The chemo- and regioselective sequential introduction of four substituents to the scaffold rapidly afforded the desired, structurally diverse 1,5,7-trisubstituted-3-pyridyl-xanthones. An evaluation of insecticidal activity revealed that one of the synthesized compounds retained insecticidal activity against vetch aphid and green peach aphid. The observed insecticidal spectrum was similar to that of pyripyropene A. The developed template could be a valuable aid for future agrichemical development.

Self-Assembly of Nanometer-Sized Boroxine Cages from Diboronic Acids.

By use of the reversible trimerization of boronic acids, the series of boroxine cages 3-mer, 6-mer, and 12-mer were constructed from rationally designed diboronic acids whose bond angles between two C-B bonds are 60°, 84°, and 117°, respectively. Boroxine cages 6-mer and 12-mer have 1.5 and 2.5 nm sized cavities, respectively.

Directing/protecting-group-free synthesis of tetraaryl-substituted pyrazoles through four direct arylations on an unsubstituted pyrazole scaffold.

A directing/protecting-group-free synthesis of 1,3,4,5-tetraaryl-substituted pyrazoles was achieved through four transition metal-catalyzed direct arylations. Various pyrazoles with four different aryl rings were obtained using readily available reagents from an unsubstituted pyrazole. Two aryl-substituted pyrazoles showed intense violet fluorescence, high quantum yields (Φf =0.68, 0.64), and large Stokes shifts (19000, 15200 cm(-1) ).

Concise Synthesis and Facile Nanotube Assembly of a Symmetrically Multifunctionalized Cycloparaphenylene.

The concise synthesis of C3-symmetrical [12]CPP-hexacarboxylate has been achieved through macrocyclization by the rhodium-catalyzed intermolecular cross-cyclotrimerization and subsequent reductive aromatization. C3-Symmetrical functionalization of CPP with highly polar alkoxycarbonyl groups enabled the structurally uniform nanotube assembly in the crystalline state through multiple hydrogen-bonding interactions giving a dimer followed by one-dimensional stacking.

Asymmetric Total Synthesis of ent-Pyripyropene†A.

An asymmetric total synthesis of ent-pyripyropene A was achieved by a convergent synthetic route. We used our originally developed Ti(III) -catalyzed radical cyclization to construct an AB-ring portion that consisted of a trans-decalin skeleton with five contiguous stereogenic centers. The coupling between the AB-ring and the DE-ring portions, and a subsequent C-ring cyclization, led to the total synthesis of ent-pyripyropene A. An evaluation of the insecticidal activity of ent-pyripyropene A against two aphid species revealed that ent-pyripyropene A was 35-175 times less active than naturally occurring pyripyropene A. This result indicated that the biological target of pyripyropene A recognizes the absolute configuration of pyripyropene A.

Transient protection of strained alkynes from click reaction via complexation with copper.

A transient protection method of cyclooctynes from a click reaction with an azide through 1:1 complexation with a cationic copper(I) salt is reported. The application of the method to a cyclooctyne bearing a terminal alkyne enabled the selective copper-catalyzed click conjugation with an azide at the terminal alkyne moiety, which made cyclooctyne derivatives readily accessible.

Inclusion of two different guest molecules within a rationally designed macrocyclic boronic ester in organic solvent.

The inclusion of two different guest molecules in a macrocyclic boronic ester in organic solvent utilizing only π-stacking interactions has been successfully realized. For this purpose, a new tetrol which has an appropriate distance between two 1,2-diol units for the inclusion of two aromatic molecules is designed and synthesized. Simple mixing of the new tetrol with 2,7-pyrenediboronic acid in the presence of pyrene-4,5-quinone efficiently affords the desired macrocyclic boronic ester, which is found by (1)H NMR spectroscopy, ESI-MS, and isothermal titration calorimetry studies to include one molecule each of a dinitronaphthalimide derivative and pyrene. Furthermore, inclusion of two planar molecules within the macrocyclic boronic ester is revealed by X-ray analysis.

Absolute asymmetric photocyclization of triisopropylbenzophenone derivatives in crystals and their morphological changes.

Although 4-(2,4,6-triisopropylbenzoyl)benzylbenzamide is an achiral molecule, chiral crystals can form through spontaneous crystallization in a methanol solution. In the M crystal, twofold helical hydrogen-bond chains form in a counterclockwise direction among the molecules along the a axis to generate crystal chirality. The solid-state circular dichroism spectra of the two enantiomorphous crystals as Nujol mulls show a good mirror-image relationship. UV irradiation of the M crystal at >290 nm caused highly enantioselective Norrish type II photocyclization to yield the (R)-cyclobutenol with 94% ee in 100% yield as the sole product, resulting in successful absolute asymmetric synthesis. In contrast, the (S)-cyclobutenol was obtained from the P crystal with 95% ee in 100% yield. The high enantiodifferentiation in the crystalline-state photocyclization is attributed to the shorter distance between the carbonyl oxygen atom and one of the methine γ-hydrogen atoms of the two o-isopropyl groups as well as the smooth transformation with minimum molecular motion because of the similar shapes of the reactant and product molecules. UV irradiation of the platelike crystals resulted in a crack in the direction perpendicular to the long axis (the a axis of the unit cell), likely because the hydrogen-bond chains were broken during the photocyclization.

Relation between photochromic properties and molecular structures in salicylideneaniline crystals.

The crystal structures of the salicylideneaniline derivatives N-salicylidene-4-tert-butyl-aniline (1), N-3,5-di-tert-butyl-salicylidene-3-methoxyaniline (2), N-3,5-di-tert-butyl-salicylidene-3-bromoaniline (3), N-3,5-di-tert-butyl-salicylidene-3-chloroaniline (4), N-3,5-di-tert-butyl-salicylidene-4-bromoaniline (5), N-3,5-di-tert-butyl-salicylidene-aniline (6), N-3,5-di-tert-butyl-salicylidene-4-carboxyaniline (7) and N-salicylidene-2-chloroaniline (8) were analyzed by X-ray diffraction analysis at ambient temperature to investigate the relationship between their photochromic properties and molecular structures. A clear correlation between photochromism and the dihedral angle of the two benzene rings in the salicylideneaniline derivatives was observed. Crystals with dihedral angles less than 20° were non-photochromic, whereas those with dihedral angles greater than 30° were photochromic. Crystals with dihedral angles between 20 and 30° could be either photochromic or non-photochromic. Inhibition of the pedal motion by intra- or intermolecular steric hindrance, however, can result in non-photochromic behaviour even if the dihedral angle is larger than 30°.

Synthesis of Dibenzofurans by Cu-Catalyzed Deborylative Ring Contraction of Dibenzoxaborins.

An efficient transformation of dibenzoxaborins to dibenzofurans by deborylative ring contraction was achieved under mild conditions using a copper catalyst. The method showed a broad substrate scope enabling the preparation of various dibenzofurans, including those bearing a functional group. The ready availability of various dibenzoxaborins enhances the utility of this method, as demonstrated by the regiodivergent synthesis of dibenzofurans.

Switching of the solid-state guest selectivity: solvent-dependent selective guest inclusion in a crystalline macrocyclic boronic ester.

Selective inclusion of each of bicyclic and tricyclic aromatic guest molecules was realized utilizing the self-assembly of a crystalline benzothiadiazole-type macrocyclic boronic ester. The complete switching of the guest selectivity was achieved simply by changing the cosolvent used in the formation of the crystalline host-guest complexes. Both the association free energy of host-guest complexes and the stability of packing structure were found to play important roles for the determination of the guest selectivity in this system, and the critical role of solvent molecules in the crystalline state for the switching phenomena was clarified.

Sequential S(N)Ar Reaction/Suzuki-Miyaura Coupling/C-H Direct Arylations Approach for the Rapid Synthesis of Tetraaryl-Substituted Pyrazoles.

A rapid synthesis of 1,3,4,5-tetraaryl-substituted pyrazoles has been achieved through a sequence of SN Ar reaction/Suzuki-Miyaura coupling/Pd-catalyzed direct arylations that used 3-iodo-1H-pyrazole as a scaffold. Pyrazoles with four different aryl groups were synthesized in a straightforward manner with no extra synthetic steps, such as protection/deprotection or the introduction of activating/directing groups, using readily available substrates and reagents. The developed synthetic approach enabled the structurally diverse synthesis of multiaryl-substituted pyrazoles without using a glovebox technique.

Solid-State Polycondensation via Ionic-to-Covalent Bond Transformation to Control Polymer Structure: Preparation of Porphyrin-Based Ladder Polymer.

The controlled formation and the regular arrangement of polymer chains have been performed by novel solid-state polycondensation including the ionic-to-covalent bond transformation in the ionic molecular crystals. The combination of the tetra-anion and -cation of tetraphenylporphyrin derivatives, tetrakis(benzylpyridinium carboxylate), was found to form layered crystal structures and underwent thermal solid-state polycondensation, thus, releasing the pyridine and forming the benzyl ester linkages. Powder X-ray diffraction, when compared to the monomer crystal structure data, suggested that the ladder polymer was produced with a layered structure.

Novel terpenes generated by heterologous expression of bacterial terpene synthase genes in an engineered Streptomyces host.

Mining of bacterial genome data has revealed numerous presumptive terpene synthases. Heterologous expression of several putative terpene synthase genes in an engineered Streptomyces host has revealed 13 newly discovered terpenes whose GC-MS and NMR data did not match with any known compounds in spectroscopic databases. Each of the genes encoding the corresponding terpene synthases were silent in their parent microorganisms. Heterologous expression and detailed NMR spectroscopic analysis allowed assignment of the structures of 13 new cyclic terpenes. Among these newly identified compounds, two were found to be linear triquinane sesquiterpenes that have never previously been isolated from bacteria or any other source. The remaining 11 new compounds were shown to be diterpene hydrocarbons and alcohol, including hydropyrene (1), hydropyrenol (2), tsukubadiene (11) and odyverdienes A (12) and B (13) each displaying a novel diterpene skeleton that had not previously been reported.

Procedure-dependent construction of two isomers of trimeric self-assembled boronic esters.

A procedure-dependent selective construction of two isomers of trimeric boronic esters was realized. A capsule-like trimeric boronic ester was constructed by the direct connection of two kinds of self-assembled boronic esters via [3+2] cycloaddition, while the tricyclic trimeric boronic ester was obtained by the self-assembly of pre-connected components.

Boron-selective biaryl coupling approach to versatile dibenzoxaborins and application to concise synthesis of defucogilvocarcin M.

An efficient synthetic method for versatile dibenzoxaborins based on boron-selective Suzuki-Miyaura cross-coupling between o-borylphenols and aryl halides or triflates bearing a 1,8-diaminonaphthalene-protected o-boryl group is reported. A short synthesis of defucogilvocarcin M was achieved using the proposed method in combination with several other boron-mediated transformations.

Design and synthesis of 2-phenyl-1,4-dioxa-spiro[4.5]deca-6,9-dien-8-ones as potential anticancer agents starting from cytotoxic spiromamakone A.

The spirocycle is a key structure found in many bioactive compounds. From the cytotoxic and spirocyclic natural product, spiromamakone A (1) and its analogues, a more synthetically accessible spiroacetal template 4 was designed based on structural similarity analysis. A total of 50 compounds were rapidly synthesized in only one or two synthetic steps from the starting compound, and their cytotoxicity was evaluated. As a result, (±)-(2R*,5R*)-2-(4-iodophenyl)-7-chloro-1,4-dioxa-spiro[4.5]deca-6,9-dien-8-one (7d-II) was discovered and found to be fifteen-fold more cytotoxic than 1. The easily accessible spiroacetal 7d-II appeared to act in a manner similar to the highly oxidized natural product, spiromamakone A (1).

Enhanced clickability of doubly sterically-hindered aryl azides.

Steric character is one of the most fundamental factors to determine the reactivity of the substrate in organic synthesis. In bimolecular reaction, the sterically-bulky group situated close to the reactive center generally prevents the approach of the reaction partner retarding the bond formation. This report describes, to the contrary, significantly enhanced reactivity of 2,6-disubstituted phenyl azides observed in catalyst-free 1,3-dipolar cycloaddition with alkynes, unexpectedly reacting faster than unsubstituted phenyl azide and even more faster than unhindered alkyl azide, despite the steric hindrance adjacent to the reactive azido group. Experimental and computational studies have indicated that the steric hindrance eliciting the inhibition of resonance between azido group and the aromatic ring is the primary cause of this apparently-paradoxical phenomenon. This is the first type of steric acceleration, indicating a possibility of designing a highly reactive functional group by strategically locating it in the sterically-congested environment.