The structure-activity relationship of aryloxyacetylthioureas for the inhibition of Orobanche minor radicle elongation.

Orobanchaceae root parasitic weeds cause significant damage to agriculture and become threats to global food security. Integrated pest management is a key concept in modern agriculture and requires chemicals with various modes of action. Planteose accumulates as a storage carbohydrate in the dry seeds of root parasitic weeds. In Orobanche minor seeds, planteose is hydrolyzed by an α-galactosidase, OmAGAL2, during germination. It was found that the OmAGAL2 inhibitor, PI-28, suppressed the radicle elongation of germinating O. minor seeds. This inhibitory activity against O. minor radicle elongation was evaluated for a series of aryloxyacetylthioureas synthesized based on the structure of PI-28. Compounds with a 3-Cl or 4-Cl substituent on the benzene ring in the phenoxy moiety in PI-28 exhibited more potent activity than the parent PI-28. This is the first report on the effect of aryloxyacetylthioureas on a root parasitic weed and will contribute to the development of control reagents for root parasitic weeds.

Access to γ-Carbolines: Synthesis of Isocryptolepine.

A new method to synthesize γ-carboline derivatives has been developed starting from 3,5-dibromo-4-pyridinamine by monoarylation using the Suzuki-Miyaura cross-coupling reaction followed by the base-mediated ring closure to pyrrole formation. Synthesis of a series of γ-carboline derivations from the 4-brominated γ-carboline 4a has been achieved by employing various coupling reactions and N-alkylations. This method has been applied for the synthesis of the antimalarial and anticancer natural product isocryptolepine. The photophysical properties of novel γ-carboline derivations are also reported.

Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1.

Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1) has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2)c cells by measuring HIF response element (HRE) promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity.

Palladium-Catalyzed Cyanothiolation of Internal Alkynes Using Organic Disulfides and tert-Butyl Isocyanide.

Despite the availability of selective synthetic approaches to multifunctionalized substituted olefins, the cyanothiolation of internal alkynes has been much less explored. Herein, we show that nonactivated internal alkynes can be successfully cyanothiolated with diaryl disulfides and tert-butyl isocyanide in the presence of a Pd catalyst (e.g., Pd(PPh3)4) with the release of isobutene and arenethiol to afford ß-thiolated alkenyl cyanides in yields of 34-89%.

A Benzoyl Peroxide/Diphenyl Diselenide Binary System for Functionalization of Alkynes Leading to Alkenyl and Alkynyl Selenides.

Binary systems consisting of benzoyl peroxide (BPO) and diorganyl diselenide are effective in the selective benzoyloxyselenation of internal alkynes to afford the corresponding ß-(benzoyloxy)alkenyl selenides in good yields. In contrast to internal alkynes, terminal alkynes undergo a novel C(sp)-H substitution with the phenylseleno group of the BPO/(PhSe)2 system, providing alkynyl selenides in good yields. Both selenation reactions might proceed via benzoyloxy selenide (PhC(O)O-SeAr) as a key intermediate for electrophilic addition to alkynes. The products alkenyl and alkynyl selenides are expected to be useful synthetic intermediates in organic synthesis.

Sequential Synthesis, Olfactory Properties, and Biological Activity of Quinoxaline Derivatives.

A simple, practical, and rapid access to quinoxalin-2-ones 1, 1,2,3,4-tetrahydroquinoxalines 2, quinoxalines 3, and quinoxalin-2(1H)-ones 4 has been achieved, based on the copper-catalyzed quinoxalinone formation of 2-haloanilines and amino acids followed by their reduction and oxidation. The olfactory properties and lipid accumulation inhibitory activity in cultured hepatocytes of the quinoxaline derivatives were also evaluated.

A facile and rapid access to resveratrol derivatives and their radioprotective activity.

A facile and rapid access to resveratrol derivatives has been achieved based on palladium-catalyzed oxidative Heck reaction of aryl boronic acids with styrenes followed by demethylation in moderate to good yields. A series of resveratrol derivatives with various functional groups has been synthesized easily. The radioprotective activity of synthesized compounds has also been evaluated using rat thymocytes. The results revealed that some resveratrol derivatives efficiently protected the thymocytes from radiation-induced apoptosis.

Proline-Mediated Transition Metal-Free Access to 1H-Indazolones from 2-Halobenzohydrazides.

Transition metal-free access to 1H-indazolones 1 has been achieved on the basis of base-mediated intramolecular C-N bond formation. Reactions of 2-halobenzohydrazides 2 with potassium tert-butoxide in the presence of catalytic proline provided indazolones 1 in moderate to good yields. This transformation may proceed primarily via the radical pathway according to the control experiment with a radical scavenger.

Molecular propellers that consist of dehydrobenzo[14]annulene blades.

A new class of propel- ler-shaped compound (4), which consisted of dehydrobenzo[14]annulene ([14]DBA) blades, as well as its naphtho homologues (5 and 6), have been prepared. Although NMR studies of compound 4 did not provide useful information regarding its conformation in solution, DFT calculations with different functionals and the 6-31G* basis set all indicated that the D(3)-symmetric structure was energetically more favorable than the C(2) conformer. From X-ray crystallographic analysis, it appeared that compound 4 adopted a propeller-shaped-, approximately D(3)-symmetric structure in the solid state, in which the [14]DBA blades were twisted substantially owing to steric repulsion between the neighboring benzene rings. On the contrary, in the case of compound 6, although the DFT calculations with the B3LYP functional predicted that the D(3)-symmetric conformation was more stable, calculations with the M05 and M05-2X functionals indicated that the C(2) conformer was more favorable because of π-π interactions between the naphthalene units of a pair of neighboring blades. Indeed, X-ray analysis of compound 6 showed that it adopted an approximately C(2)-symmetric conformation. Moreover, on the basis of variable-temperature (1)H NMR measurements, we found that compound 6 adopted a C(2) conformation and the barrier for interconversion between the C(2)-C(2) conformers was estimated to be 16.2 kcal mol(-1); however, no indication of the presence of the D(3) isomer was obtained. The relatively small energy barriers to interconversion, despite the large overlapping of neighboring blades, was ascribed to the flexibility of the acetylene linkages, which could be deformed substantially in the transition state of the ring-flip.

Highly regioselective simultaneous introduction of phosphino and seleno groups into unsaturated bonds by the novel combination of (Ph2P)2 and (PhSe)2 upon photoirradiation.

A novel combination of tetraphenyldiphosphine and diphenyl diselenide under photoirradiation conditions attains simultaneous introduction of diphenylphosphino and phenylseleno groups into carbon-carbon unsaturated bonds such as terminal alkynes or allenes, regioselectively.

Donors and acceptors based on triangular dehydrobenzo[12]annulenes: formation of a triple-layered rosette structure by a charge-transfer complex.

We present here the results of studies of the synthesis and properties of donors and acceptors based on triangular dehydrobenzo[12]annulene ([12]DBA) system as a pi core. These studies were aimed at controlling the supramolecular crystal structure. Toward this end, the tricyano[12]DBA 2 and dodecafluoro[12]DBA ( 3) were synthesized as acceptors (A) and the tris(dialkylamino)[12]DBAs 4a-d as donors (D), and their electronic properties were determined by electronic absorption spectroscopy and electrochemical measurements. The main focus, though, was the formation of supramolecular structures in crystals. These compounds form distinct packing patterns as a result of the different intermolecular interactions. Tricyano[12]DBA 2 forms a two-dimensional (2D) sheet structure via hydrogen-bonding interactions, whereas a tilted-stack structure was found for 3 because of the lack of significant intermolecular interactions. Tris(dibutylamino)[12]DBA 4b exhibits a ladder-type 2D structure, probably because of van der Waals interactions between the butyl groups. The most significant finding is that charge-transfer interactions between donor 4a and acceptor 3 combined with their triangular molecular shapes and lateral CH...F hydrogen bonding result in the formation of a 2D rosette structure consisting of two different trimeric (DAD- and ADA-type) sandwich structures with 1:2 and 2:1 A/D ratios, respectively.

A highly regioselective palladium-catalyzed hydrophosphination of alkynes using a diphosphine-hydrosilane binary system.

A novel transition-metal-catalyzed hydrophosphination of terminal alkynes using a diphosphine-hydrosilane binary system takes place regioselectively to provide vinylic phosphines, which undergo air oxidation during workup, affording the corresponding vinylphosphine oxides in good yields. In this hydrophosphination, hydrosilanes act as a useful hydrogen source, and furthermore, small amounts of oxygen is required to accomplish the reaction efficiently.

Site-selective guest inclusion in molecular networks of butadiyne-bridged pyridino and benzeno square macrocycles on a surface.

We present here the formation of a modular 2D molecular network composed of two different types of square-shaped butadiyne-bridged macrocycles, having intrinsic molecular voids, aligned alternately at the solid-liquid interface. Site-selective inclusion of a guest cation took place at every other molecular void in the molecular network with two different recognition sites.

Two-photon absorption properties of Dehydrobenzo[12]annulenes and hexakis(phenylethynyl)benzenes: effect of edge-linkage.

Two-photon absorption (TPA) properties of two trefoil-shaped compounds with different edge linkages--tris(hexadehydrotribenzo[12]annulene) and tris(tetradehydrotribenzo[12]annulene)--and three asterisk-shaped compounds having no edge-linkage--hexakis(phenylethynyl)benzenes--are investigated experimentally by the open-aperture Z-scan and TPA-induced fluorescence methods with wavelength tuneable femtosecond pulses. The compound with ethynylene edge-linkage exhibits the most intense TPA (the maximal TPA cross section is 1300+/-170 GM at 572 nm where 1 GM=10(-50) cm(4) s molecule(-1) photon(-1)). The TPA activity of the compounds is primarily explained in terms of the planarity of the molecules in relation with the type of edge-linkage.

Synthesis of dehydrobenzo[18]annulene derivatives and formation of self-assembled monolayers: implications of core size on alkyl chain interdigitation.

The synthesis of a series of dodecadehydrotribenzo[18]annulene ([18]DBA) derivatives is reported, together with their steady-state absorption and fluorescence properties. The main focus, though, is on the self-assembly of these compounds at the liquid-solid interface as investigated with scanning tunneling microscopy (STM), highlighting the effect of alkyl chain orientation and alkyl chain length on the molecular ordering. Owing to the large triangular pi-electron system of the [18]DBAs, two different types of alkyl chain orientation are observed. The observed changes in the monolayer networks upon elongation of the alkyl chains are attributed to the increased van der Waals interactions between molecules and substrate. The effect of the core size on the alkyl chain orientation and, as a result, the monolayer structure is discussed in relation to the results obtained previously for triangularly-shaped dehydrobenzo [12]annulene ([12]DBA) derivatives and triphenylene derivatives. A guideline for substituent spacing allowing control of molecular alignment for large planar pi-electron systems utilizing directional alkyl chain interdigitation is also discussed.

Theoretical studies on graphyne substructures: geometry, aromaticity, and electronic properties of the multiply fused dehydrobenzo[12]annulenes.

The geometries of multiply fused dehydrobenzo[12]annulenes [12]DBAs 2-7 with various topologies, which are considered as graphyne fragments, have been optimized at the B3LYP/6-31G* level of theory. Most of the optimized geometries of fused DBAs have planar structures excluding a boomerang-shaped bisDBA 4, a trefoil-shaped trisDBA 6, and a wheel-shaped DBA 7. For the boomerang-shaped bisDBA 4 and the trefoil-shaped trisDBA 6, distortions originate from the steric repulsion between hydrogen atoms attached to adjacent benzene rings. The harmonic oscillator model of aromaticity (HOMA) values at the central benzene ring of multiply fused DBAs decrease as the number of fused 12-membered rings increases except for the closely related structures 4 and 5 and 6 and 7, because of bond length elongation due to conjugation with the phenylethynyl groups. Nucleus-independent chemical shifts (NICS) were computed at the individual ring centers of the fused DBAs. The fusion of the antiaromatic 12-membered rings results in increasing (more positive) NICS values at the central benzene ring, indicating the decrease of diatropic ring currents. Furthermore, HOMO-LUMO gaps of the DBAs 2-7 are strongly influenced by the molecular topology. The para-conjugation pathway of the bis(phenylethynyl)benzene unit plays a more important role in the determination of the electronic properties of multiply fused DBAs than the meta- and ortho-conjugation pathways.

Two-dimensional porous molecular networks of dehydrobenzo[12]annulene derivatives via alkyl chain interdigitation.

The self-assembly of a series of hexadehydrotribenzo[12]annulene (DBA) derivatives has been scrutinized by scanning tunneling microscopy (STM) at the liquid-solid interface. First, the influence of core symmetry on the network structure was investigated by comparing the two-dimensional (2D) ordering of rhombic bisDBA 1a and triangular DBA 2a (Figure 1). BisDBA 1a forms a Kagomé network upon physisorption from 1,2,4-trichlorobenzene (TCB) onto highly oriented pyrolytic graphite (HOPG). Under similar experimental conditions, DBA 2a shows the formation of a honeycomb network. The core symmetry and location of alkyl substituents determine the network structure. The most remarkable feature of the DBA networks is the interdigitation of the nonpolar alkyl chains: they connect the pi-conjugated cores and direct their orientation. As a result, 2D open networks with voids are formed. Second, the effect of alkyl chain length on the structure of DBA patterns was investigated. Upon increasing the length of the alkyl chains (DBAs 3c-e) a transition from honeycomb networks to linear networks was observed in TCB, an observation attributed to stronger molecule-substrate interactions. Third, the effect of solvent on the structure of the nonpolar DBA networks was investigated in four different solvents: TCB as a polar aromatic solvent, 1-phenyloctane as a solvent having both aromatic and aliphatic moieties, n-tetradecane as an aliphatic solvent, and octanoic acid as a polar alkylated solvent. The solvent dramatically changes the structure of the DBA networks. The solvent effects are discussed in terms of factors that influence the mobility of molecules at the liquid-solid interface such as solvation.

Synthesis and properties of trefoil-shaped tris(hexadehydrotribenzo[12]annulene) and tris(tetradehydrotribenzo[12]annulene).

[reaction: see text] Trefoil-shaped tris(hexadehydrotribenzo[12]annulene) possessing a substructure of the ultimate two-dimensional C(sp)-C(sp(2)) network, graphyne, and the related tris(tetradehydrotribenzo[12]annulene) were synthesized, and their ground- and excited-state properties were investigated.

Novel synthesis of bridged phenylthienylethenes and dithienylethenes via Pd-catalyzed double-cyclization reactions of diarylhexadienynes.

[reaction: see text] Bridged phenylthienylethenes and dithienylethenes were synthesized via Pd-catalyzed double-cyclization reactions of (Z,Z)-1,6-diaryl-1,5-hexadien-3-ynes. Pd-catalyzed as well as photoinduced Z/E isomerization of the products were also investigated.