We have studied for the total synthesis of asperterrestide A, which is a cyclic tetrapeptide natural product reported to be composed of D-alanine, anthranilic acid, (2R,3S)-3-hydroxy-N-methylphenylalanine, and D-isoleucine or D-allo-isoleucine. We initially performed the total synthesis of the reported structure of asperterrestide A via solid-phase peptide synthesis and macrocyclization in solution. However, the spectral data of the synthetic (9R,25R)-derivative did not match those of the natural product. Then, we considered the true structure should be the (9S,25S)-stereoisomer because all NOE correlations predicted from its three-dimensional structures obtained by theoretical calculations were consistent with those observed in the natural product. Thus, the (9S,25S)-stereoisomer was synthesized through solution-phase synthesis because N-acylation of a polymer-supported (2S,3S)-3-hydroxy-N-methylphenylalanine derivative resulted in low yield. The (9S,25S)-stereoisomer was successfully synthesized and was found to be identical to the natural product. Therefore, the stereochemical configuration of asperterrestide A was corrected from (9R,25R) to (9S,25S). We also tested whether the DFT calculation of carbon chemical shifts can discriminate stereoisomers of cyclic tetrapeptides. After conformational analysis of four possible stereoisomers of asperterrestide A, Boltzmann-weighted carbon chemical shifts based on DFT calculations using Spartan’20 revealed a DP4 accuracy of 96%, which is sufficient to determine the stereochemical configuration among the stereoisomers. In addition, three 9-deoxy derivatives were synthesized and the cell growth inhibitory activity of the five synthetic compounds against human cancer cells (U937, MOLT-4, and A549) was evaluated. The results showed that the (9S,25S)-stereoisomer is as potent as asperterrestide A, whereas the (9R,25R)-derivative is not. The (9S,25S)-3-deoxy analogs were found to be equipotent to the natural product although the activity of the (9S,25R)-deoxy analog was lost.

Furoxan (1,2,5-oxadiazole-2-oxide), categorized into a heteroaromatic compound, is a potentially useful drug-like molecule. However, due to the vulnerability of furoxan rings to ring-opening under various reaction conditions, there have been sporadic reports on its efficient synthesis; therefore, applied research on furoxan is relatively unexplored. We report herein our recent contribution to this research area. The unique photo-induced nitric oxide donors based on furoxan architecture are also represented.

In this paper, a nonstoichiometric Migita-Kosugi-Stille coupling polycondensation based on intramolecular catalyst transfer systems has been reviewed. The achievement of those systems is significant from the viewpoints of (1) acquisition of new knowledge in the synthesis of semiconducting polymer materials, (2) unnecessary strict control in monomer feed ratios generally required for a single-phased solution polycondensation, (3) possible improvement of the monomer reactivity by varying feed ratios, and (4) possibility of controlled chain end groups and extension to the synthesis of all-conjugated block copolymers. In practice, naphthalene-diimide-, phthalimide-, and terephthalate-based π-conjugated polymers have been synthesized under imbalanced stoichiometric conditions, possessing much higher molecular weights than those based on Carothers/Flory’s theory. The results of various model reactions and DFT calculations have revealed that the origin of the intramolecular catalyst transfer phenomenon is related to the existence of carbonyl groups introduced at the ortho-position of dibromo aryl monomers used in excess as well as types of palladium catalysts/precatalysts. In the near future, the proposed nonstoichiometric Migita-Kosugi-Stille coupling polycondensation will be established by extending the adaptable monomers and further optimizing catalysts/precatalysts.

Direct transformation of unactivated bond such as C-H bond is an important transformation. Because of its high utility from the viewpoints of atom economy and step economy, much effort has been devoted to the development of novel and more efficient strategies. Most of the reported processes have been relied on the use of active, transition metal (TM) catalysts. Unfortunately, this chemistry is hounded by the problem that stoichiometric amounts of oxidants, which become waste after the reaction, are required for the regeneration of the active oxidation state of TM. Needless to say, the use of toxic TM catalysts is also negative point from the economic and practical points of view. We have developed a novel type of C(sp³)-H bond functionalization without external oxidants, and, in some cases, TM catalysts. The key of this reaction is an intramolecular redox process, which is induced by intramolecular hydride shift. This reaction has several useful features: (1) the reaction proceeds via internal redox process, and hence, external oxidants are not required, (2) functionalization of the most tough C-H bond, C(sp³)-H bond, is involved, (3) three dimensional cyclic structures containing chiral centers are produced from non-chiral, linear substrates, (4) functionalization of remote C-H bond (more than five-atoms apart) is achieved. In this article, we want to describe the details of our endeavors to develop the target reactions, and its application to the construction of various useful fused-cycles which are otherwise difficult to achieve by the conventional methods.

Substituted polyacetylene derivatives are promising π-conjugated materials, which can be synthesized by polymerization of the corresponding substituted acetylenes by transition metal catalysis. Rhodium(I) complexes have been widely used for the polymerization of monosubstituted acetylenes such as phenylacetylene derivatives because they are functional group tolerant and provide cis-stereoregular polymers. There are some examples of well-controlled polymerization of phenylacetylene derivatives using well-defined rhodium(I) complexes as initiators. However, versatile design of polymer end structures is difficult in such known methods because initiators having various functional groups are not easily available. To overcome such a problem, we have developed a new method for well-controlled polymerization of phenylacetylene derivatives using a multicomponent catalytic system composed of bicyclo[2.2.1]hepta-2,5-diene-rhodium(I) chloride dimer [Rh(nbd)Cl]₂, arylboronic acids, diphenylacetylene and 50% aqueous solution of KOH. This polymerization method showed a typical living nature, and structures derived from aryl boronic acids and diphenylacetylene were introduced to the initiating end of the obtained polymers. Moreover, functionalization of the polymer terminal end could be achieved by reactions of the living polymer terminus with α,β-unsaturated carbonyl compounds such as acrylates, and various telechelic poly(phenylacetylene)s were obtained. Novel 1,3,5-hexatrienylrhodium(I) complexes were isolated from the present multicomponent catalytic system, and their structures were identified. When [Rh(nbd)Cl]₂ was replaced with hydroxy(1,5-cyclooctadiene) rhodium(I) dimer ([Rh(cod)OH]₂) in the present catalytic system, cyclobutenylrhodium(I) complexes were exclusively obtained. These complexes provided insights into the initiation mechanism in the living polymerization. The present catalytic system was applied to the living polymerization of water-soluble phenylacetylene derivatives and non-conjugated monosubstituted acetylenes such as N-propargylamides.

Aromaticity is an important concept that controls the stability, electronic property and reactivity of π-conjugated compounds. The conventional understanding of aromaticity, however, often fails to explain the behavior of compounds with highly complicated networks. This review highlights the recent development of syntheses of 3D π-conjugated macrocycles and discussions about aromaticity in 3D π-conjugated systems.