Natural products are a rich source of biologically active compounds that are frequently developed into pharmaceutical medicines. Synthetic organic chemistry has contributed to bridge medicinal and natural product chemistries by broadening the accessible chemical entities based on the structure of natural products. In this article, we describe our recent achievements in catalytic asymmetric total synthesis of biologically active natural products with structural complexity.
Caprazamycin B was discovered as an anti-tuberculosis antibiotic, and was developed to CPZEN-45, which exhibited activity toward extensively drug-resistant strains (XDR-TB). Leucinostatin A exhibited selective antiproliferative activity against tumor cells in the presence of the corresponding stromal cells, which can be recognized as an anti-cancer seed. To facilitate structure activity relationship studies, synthetic routes to both natural products were established using catalytic asymmetric reactions as key transformations to regulate the absolute configuration. A nitroaldol reaction using Nd/Na-amide complex or LLB*, a thioamide-aldol reaction with Cu(I) complexed with a chiral bidentate phosphine ligand, alcoholysis of 3-glutaric anhydride employing a Ni2-Schiff base complex, a Zn-linked BINOL-catalyzed aldol reaction, and a Strecker-type reaction were effectively applied to the syntheses. It is noteworthy that the present syntheses revised the reported stereochemistry of leucinostatin A.
In recent years, fluorescent nucleobase analogs have received a great deal of attention due to their unique photophysical properties as well as their potential usefulness as probes for the higher order structures of nucleic acids. One of the approach to develop fluorescent nucleobase is to directly attach a heteroaromatic group to a nucleobase. Because the heteroaromatic group introduced to the nucleobase can freely rotate, the photophysical properties of the fluorescent nucleobase, thus developed, can change depending on the environment or the interaction with other molecules which affect the rotation of the heteroaromatic group. Such environment sensitive fluorescent bases are called ‘molecular rotors’, and expected as the useful fluorescent probes for monitoring the nucleic acids-nucleic acids interactions or nucleic acids-protein interactions. This article describes the synthesis and photophysical properties of the ‘molecular rotor’ fluorescent nucleobases developed by us. Especially, the uracil derivatives bearing a benzofuran or a 3-methylbenzofuran ring at the position 5, and 7-deazaguanine derivative bearing a benzofuran ring at the position 7 are described. In addition, a unique fluorescent uracil derivative bearing 3-(4-hydroxybenzilidene)imidazolinone skeletones, which are mimic of chromophore of green fluorescent protein, at the position 5 is also described.
We describe the total synthesis of indolo[2,1-b]quinazoline alkaloids tryptanthrin (1a), candidine (2), phaitanthrins A (3), B (4), C (5), cruciferane (8), and cephalanthrin A (9) using oxidative cascade sequences as the key step. Phaitanthrin E (7a) was synthesized by a novel methodology that features a concise approach involving the intermolecular condensation and intramolecular aryl C-H amination mediated by Cu-complexes to construct the indolo[2,1-b]quinazoline core. Moreover, an acid catalyzed one-pot synthesis of phaitanthrin E (7a) via intermolecular amination/intramolecular cyclization cascade using NCS was also developed.
The desymmetrization of meso compounds is one of the most effective strategies for asymmetric synthesis. We introduce the current progress of this area, which covers the methods for (1) enzymatic acylation of meso-diols and the hydrolysis of meso-diesters, acylation, related reactions of meso-diols with organocatalysts and metal catalysts, (2) oxidation of meso-diols by enzymes, organocatalysts, and metal catalysts. The tandem reactions based on the desymmetrization of meso-diols is also included.
Azulene is a simple substance belonging to the class of compounds known as non-benzenoid aromatic hydrocarbons, and has attracted much attention because of its unusual properties, typified by large dipole moment and long-wavelength absorption properties. In this paper, we describe the synthesis, structures, properties, and organic field-effect transistor (OFET) characteristics of 2-azulenyl end-capped oligomers and 2,6-connected terazulene isomers. These compounds showed small transition energies due to their effective π-conjugation system, high-order orientations in the crystalline state, and typical OFET characteristics with high carrier mobilities. In particular, terazulene isomers reveal a unique π-conjugation system with an asymmetric distribution of molecular orbitals, which present an unconventional concept: polarity control of OFET achieved by molecular orbital distribution control. The molecular design, based on the 2,6-connected azulene-based π-conjugation, could be a key approach for constructing various semiconductor materials. Moreover, these findings provide a basis for accelerated development of the solid-state chemistry of azulene.
This review describes palladium-catalyzed reactions of allylic compounds via π-allyl-palladium intermediate using hydrazone ligand. Generally, phosphine-type ligands were utilized for palladium-catalyzed reaction of allylic compounds. We found that allylic arylation of allylic ester with aryl boronic acids proceeded smoothly at room temperature and afforded 1,3-diarylpropene derivatives using phosphine-free hydrazone-palladium catalyst system. Moreover, we demonstrated that allylic arylation of allylic aryl ether also proceeded smoothly using this catalyst system. Inspired from this reaction, we found hydrazone-palladium catalyzed one-molecular reaction of allyloxyphenylboronic acid derivatives bearing allylic aryl ether moiety and arylboronic acid moiety afforded the corresponding allylphenol derivatives. Furthermore, we demonstrated that hydrazone ligand was more effective than phosphine-type ligand for palladium-catalyzed annulation via coordinating of π-allyl-palladium intermediate to triple bond electrophilically.
Unlike classical polymers consisting of monomer units connected by a single covalent bond, ladder polymers having two covalent bonds between repeating units are considered to be new materials showing high thermal stability, and intrinsic porosity. In this mini-review, I focus recent synthetic/structural development of ladder polymers; 1. Pd catalyzed annulation reaction, 2. olefin metathesis reaction, and 3. a synthetic methodology for flexible ladder polymers. These developments will enable ladder polymers to apply for innovative porous materials, thin-film devices, and adhesive materials.
Forty years have passed since the first personal computers were commercially launched. The computation rate has tremendously increased; the present desktop computers perform calculations over two thousand times faster than those in the late 1970s for the CPU clockwise. Present desktop computers deal with 1,000 times larger data at once than those in the early desktops. In addition to those, the remarkable progress of molecular modeling methods involving density functional theory (DFT) has enabled us to estimate the NMR and CD spectra in very high quality. This lounge introduces the basic properties of DFT computation, the hardware required for the calculations, and the several points we need to be careful in focusing on structural elucidations of natural products. This lounge also demonstrates the applications of DFT calculations in the structural elucidations of neomacrophorin X and cyclohelminthol X as the examples.