The first total synthesis of dendrochrysanene (1) was achieved. The key reaction for the construction of dendrochrysanene was an oxidative frame rearrangement reaction from a phenanthrene dimer to a spiro-lactone skeleton, which we serendipitously identified. Owing to the steric hindrance of the substituent on the peri position of the phenanthrene dimer, high-temperature conditions were required for the rearrangement reaction; however, at such temperatures, the substrate decomposed. To address this issue, we added phenylethylamine or benzylamine to the reaction system. We assumed that the amine trapped generated hydrochloric acid and acted as a ligand for iron, helping to maintain an appropriate redox potential. The total synthesis of dendrochrysanene, involving this rearrangement reaction, is an important sequence interlinking phenanthrene derivatives, phenanthrene dimers, and spiro-lactone compounds, which are frequently isolated from plants of Orchidaceae.

A [12]Cyclo-p-phenylene 9 composed of dinaphthofuran units and biphenyl units was synthesized through reductive elimination of the corresponding trinuclear complex by applying Yamago’s method. The X-ray crystallographic analyses of 9 revealed that it adopts a zigzag conformation in the solid state. The UV–vis and fluorescence measurements of compound 9 indicated that it also preferentially took a zigzag conformation in the solution state.

New V-shaped xanthene dyes 3–6 containing piperidino groups at the resonance sites on their skeletons were constructed as second-generation V-shaped dyes and their functions were investigated. The non-symmetric compound 5 had higher solubility and gave a higher fluorescence quantum yield and longer emission wavelength compared with those of previously reported V-shaped xanthene dyes with hydroxyl groups 1 and 2. Furthermore, compound 5 stained living cells, enabling bright fluorescence imaging.Download high-res image (298KB)Download full-size image

exo-Alkylidene xanthenes were easily excited by irradiation with white light to generate their lowest-energy triplet state via intersystem crossing from the lowest-energy singlet state. Ground-state oxygen was then transformed by the lowest-energy triplet state of the xanthene to active singlet oxygen. The singlet oxygen reacted with the exo-alkylidene xanthene to afford the corresponding xanthone. During the transformation, the exo-alkylidene xanthenes acted as an effective photosensitizer as well as a substrate of singlet oxygen.

Unexpected dimerization of a methoxymethyl-protected xanthone occurred upon treatment with an aryl lithium reagent generated from 2-bromo-1,3-dimethylbenzene and n-butyllithium. The hydrogen between two directing ethereal oxygen atoms was not abstracted, but that adjacent to the carbonyl group was removed to afford a dimeric compound containing two directly connected fluorescent xanthone and xanthene units. Starting from this discovery, three dimeric dyes were constructed, and their optical properties were examined. Although the two fluorescent units were orthogonal in each dye, efficient energy transfer was observed in dimeric dye 16 in three solvent systems. In contrast, solvent-dependent energy transfer was detected for another dimeric dye, 5. After close investigation, we found that the orientation factor (κ) is the main factor influencing Förster resonance energy transfer in these dyes.

The construction of dinaphtho[2,1-b;2′,3′-d]furan-6-ol was developed via a dehydration reaction involving two molecules of 2,3-dihydroxynaphthalene in the presence of a strong acid. Starting from the dinaphthofuran, a variety of butterfly shaped derivatives were synthesized. The optical properties of these compounds were investigated with special attention to the dihedral angle formed by adjacent dinaphthofuran rings and/or the sizes of the fused aromatic rings.

Naphthofluorescein and/or seminaphthofluorescein derivatives possessing the additional benzene units to one or both sides of fluorescein were exhaustively constructed through Friedel–Crafts type reactions between corresponding aroylbenzoic acids and dihydroxynaphthalenes. Compound 4 works as a one-dye pH indicator, which shows red in strong acid condition and blue in basic solution. Compound 23 (diacetate of compound 4) shows good transitivity to the HEK 293 cells and acts as a fluorescent pigment for the living cell imaging. Compounds 5, 6, and 9 show fluorescent emission in the NIR region (>700 nm) and imply the potentialities of NIR fluorescent probes.

Three types of dimeric naphthoquinones, which possess structurally diverse skeletons, can be prepared in one step from 2-bromo-3-methyl-1,4-naphthoquinones. 2,2′-Dimeric naphthoquinones were prepared by a one-pot Stille-type reaction via vinylstannanes. Oxepines are formed by unexpected domino reactions via 1,4-dihydroxynaphthalene species. Epoxides are formed by a Michael/Darzens reaction via the o-quinone methides.

A highly efficient oxidative coupling of 2-naphthols and a rearrangement tandem reaction to afford unique spiro compounds in the presence of FeCl3·6H2O in up to 88% yield have been developed.

Ten vitamin K3 derivatives were synthesized and screened for anti-angiogenic activity. Results indicated that amine derivatives (1a–d) exerted a stronger inhibition effect on angiogenesis compared to alkyl derivatives (2a–d). In addition to being the most potent inhibitor, 1b also suppressed human umbilical vein endothelial cell tube formation and proliferation. These results suggest that vitamin K3 amine derivatives with shorter alkyl chains, such as 1b, could be useful for developing anti-angiogenic agents.Among the vitamin K derivatives synthesized, 1b showed the strongest anti-angiogenic effect under both ex vivo and in vitro conditions. Longer alkyl chains weaken anti-angiogenic activity.

To establish an effective and concise procedure for determining the concentrations of spermidine and spermine, several functional molecules based on phenolphthalein and two crown loops were constructed. Host 5 with a dimethylamino group showed excellent selectivity for spermidine and spermine among other biogenic amines and high sensitivity compared with basic host 1.

(S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S,S)-dotriacontanaphthalenes 32A−E alternately possessing butoxy and methoxy side chains were precisely constructed through a bottom-up synthesis, and their absolute configurations and fluorescence quantum yields were determined.

To establish an effective and concise procedure for determining the concentrations of spermidine and spermine, several functional molecules based on phenolphthalein and two crown loops were constructed. Host 5 with a dimethylamino group showed excellent selectivity for spermidine and spermine among other biogenic amines and high sensitivity compared with basic host 1.

Two new types of V-shaped dimeric xanthene fluorescent dyes were synthesized and evaluated in terms of their optical properties. Based on differences in their resonance forms, these V-shaped dyes were able to adopt four different protonation states (i.e., cationic, neutral, monoanionic and dianionic states) depending on their external environment. Notably, these compounds allowed for the bright fluorescent imaging of NIH3T3 cells when they were applied to cells as the corresponding diacetylated materials.