Hayato Ichikawa

Facile and efficient synthesis of naturally occurring carbasugars (+)-pericosines A and C.

An efficient synthesis of antitumor marine natural product (+)-pericosine A was achieved from (-)-quinic acid in 11.7% overall yield, which is 20 times better than our previously reported synthesis. The crucial steps of this synthesis include the regio- and stereoselective bromohydrination of an unstable diene and the ring opening of an epoxide. This synthetic route was applicable to a synthesis of (+)-pericosine C and also to a synthesis of (-)-pericosine C.

Design and synthesis of regioisomerically pure unsymmetrical xanthene derivatives for staining live cells and their photochemical properties

We have demonstrated the synthesis of regioisomerically pure unsymmetrical xanthene derivatives consisting of three units which can be independently modified to control their physical properties. The photochemical properties of the synthetic unsymmetrical xanthene derivatives were investigated in solution by UV-vis absorption and fluorescence measurements, and their cell imaging properties were examined by confocal laser-scanning microscopy.

Microwave-assisted selective synthesis of 2H-indazoles via double Sonogashira coupling of 3,4-diiodopyrazoles and Bergman-Masamune cycloaromatization

The microwave-assisted double Sonogashira coupling of 3,4-diiodo-1-trityl and 1-phenylpyrazole with terminal acetylene took only three minutes. Dialkynylpyrazoles, the coupling products, were heated at 240 °C in the presence of 1,4-cyclohexadiene to obtain 2H-2-trityl and 2-phenylindazoles, respectively. This synthetic route to 2H-indazole, which was achieved via cyclization to form the 6-membered ring of dialkynylpyrazole, is a novel procedure.

Remarkable catalytic activity of Me3Ga in the alkylation of hetero-substituted epoxides with alkynyllithiums

Abstract Regio- and stereoselective ring-opening reaction of hetero-substituted epoxides with alkynyllithiums can be catalyzed by Me3Ga with remarkable efficiency at 0∼20 °C via pentacoordinate chelate-type complex.

Synthesis of 4-aryl-1H-pyrazoles by Suzuki-Miyaura cross coupling reaction between 4-bromo-1H-1-tritylpyrazole and arylboronic acids

A general procedure for the synthesis of 4-aryl-1H-pyrazoles by the Suzuki-Miyaura cross coupling reaction between 4-bromo-1H-1-tritylpyrazole and commercially available arylboronic acids was developed. Using this procedure, a direct synthesis of 4-aryl-1H-pyrazoles possessing functional groups, such as hydroxyl, nitro, and amino groups, on the aryl ring was realized. Those molecules could not be prepared by our previous synthesis of 4-aryl-1H-pyrazoles via the Kumada cross coupling reaction.

Preparation and structure determination of 28-membered and 42-membered cyclic molecules linked with two or three disulfide bonds

4,7-Diethylbenzo[1,2,3]trithioles (1a–1c), 4,8-diethylbenzo[1,2-d:4,5-d′]bis[1,2,3]trithiole (1d), and 6, 10-diethyl[1,2,3]trithiolo[h]benzopentathiepin (1d′) were treated with sodium borohydride and 0.5 equiv. of p-xylylene dibromide to produce bridged molecules 2a–2d with two thiol groups. On oxidation of 2a with iodine in the presence of triethylamine, 28-membered macrocycle 3a, linked with two disulfide bonds, was obtained via a dimeric cyclization reaction, instead of a monomeric 14-membered macrocycle. Compounds 2b–2d were similarly treated with iodine and triethylamine to give 28-membered macrocycles 3b–3d. In the case of the reaction of 2c, a trimeric reaction occurred to produce 42-membered macrocycle 4 together with 3c. The structures of the cyclic molecules were determined by NMR and mass spectrometry, which was further supported by X-ray crystallographic analysis.

Synthesis of aryltetralin type 2-azalignans using Schollkopf's bislactim-ether methodology

Synthesis of (1S,3R)-2-aza-4-deoxypodophyllotoxin has been accomplished in 6 steps using Schollkopfs bislactim-ether methodology in 12% total yield. Bislactim-ether, which was originally prepared from commercially available L -valine and glycine, was used as the starting material. Our synthetic route was allied to easy access to aryltetralin type 2-azalignan analogues. Synthesized 2-azalignans were tested for in vitro anticancer activity using a panel of human cancer cell lines. Both of two (1S)-diastereomers (9a and 9b) of 2-aza-4-deoxypodophyllotoxin showed significant activity against human cancer cell lines: A-549 (lung), HTC-8 (ileocecal), and MCF-7 (breast cancer).