Eiji Ochiai

Mechanism of oxidative coupling reaction catalysed by cuprous chloride-amine complex

Abstract A study has been made on the mechanism of catalysis of cuprous chloride-amine complexes in the oxidative coupling reaction of 2,6-di(t-butyl)phenol to form 3,3′,5,5′-tetra(t-butyl) diphenoquinone. It was concluded that copper acts through the cycle of oxidation and reduction and that O 2− , which is formed by the reduction of O 2 by CU + or OH − which is added as KOH, plays an important role, perhaps, as the acceptor of proton from the phenol.

Mechanism of catalysis by metal complexes in autoxidation of an olefin

Abstract A preliminary study in the autoxidation of cyclohexene has been made of the mechanism of catalysis by transition metal stearates and phthalocyanines. A study of the working state of catalysts by absorption spectra and ESR spectral measurements during reaction has led to the conclusion that metal stearates participate in the autoxidation by the Haber-Weiss mechanism and that metal ions in two different valence states are associated, bringing about interaction absorption and ESR broadening. It is suggested that metallophthalocyanines participate in the autoxidation in several ways depending on the central metal ion.

Synthesis of 2α-heteroarylalkyl active vitamin d3 with therapeutic effect on enhancing bone mineral density in vivo.

2α-Heteroarylethyl-1α,25-dihydroxyvitamin D3 analogues, which were designed to form a hydrogen bond between Arg274 of human vitamin D receptor (hVDR) and a nitrogen atom of the heteroaromatic ring at the 2α-position, were synthesized. Among them, 2α-[2-(tetrazol-2-yl)ethyl]-1α,25-dihydroxyvitamin D3 showed higher osteocalcin promoter transactivation activity in human osteosarcoma (HOS) cells and a greater therapeutic effect in ovariectomized (OVX) rats, osteoporosis model animals, on enhancing bone mineral density than those of active vitamin D3. X-ray cocrystallographic analysis of the hVDR-ligand complex confirms that the new hydrogen bond formation stabilized the complex.

Design, synthesis and X-ray crystallographic study of new nonsecosteroidal vitamin D receptor ligands

We designed and synthesized nonsecosteroidal vitamin D receptor (VDR) ligands that formed H-bonds with six amino acid residues (Tyr143, Ser233, Arg270, Ser274, His301 and His393) of the VDR ligand-binding domain. The ligand YR335 exhibited potent transcriptional activity, which was comparable to those of 1α,25-dihydroxyvitamin D(3) and YR301. The crystal structure of the complex formed between YR335 and the VDR ligand-binding domain was solved, which revealed that YR335 formed H-bonds with the six amino acid residues mentioned above.

Development of 14-epi-19-nortachysterol and its unprecedented binding configuration for the human vitamin D receptor

In the study of the synthesis of 14-epi-19-norprevitamin D(3), we found 14-epi-19-nortachysterol derivatives through C6,7-cis/trans isomerization. We also succeeded in their chemical synthesis and revealed their marked stability and potent VDR binding affinity. To the best of our knowledge, this is the first isolation of stable tachysterol analogues. Surprisingly, 14-epi-19-nortachysterol derivatives exhibited an unprecedented binding configurations for the ligand binding pocket in hVDR, C5,6-s-trans and C7,8-s-trans triene configurations, which were opposite the natural C7,8-ene-configuration of 1α,25(OH)(2)D(3).

Synthese von derivaten der cinchona-alkaloide—XXXII : Synthese von dihydrocorynanthean und 3-epidihydrocorynanthean aus cinchonin

Abstract Starting from cinchonine, 3-epidihydrocorynantheane was synthesized through 2′-oxohexahydrocinchonine. Quinine was transformed into 10-methoxydihydrocorynantheane by the same reaction steps. In both cases, it was found that Oppenauer oxidation of the secondary hydroxyl group at quinine-numbering C-9 was accompanied with no configurational change at the neighboring C-atom, which originated from C-8 in quinuclidine moiety. 3-Epidihydrocorynantheane was converted to dihydrocorynantheane by oxidation with mercuric acetate and then sodium borohydride reduction.

New C15-Substituted Active Vitamin D3

C15-Substituted 1α,25-dihydroxyvitamin D(3) analogs were synthesized for the first time to investigate the effects of the modified CD-ring on biological activity concerning the agonistic positioning of helix-3 and helix-12 of the vitamin D receptor (VDR). X-ray cocrystallographic analysis proved that 0.6 Å shifts of the CD-ring and shrinking of the side chain were necessary to maintain the position of the 25-hydroxy group for proper interaction with helix-12. The 15-hydroxy-16-ene derivative showed higher binding affinity for hVDR than the natural hormone.

CDP/cut is an osteoblastic coactivator of the vitamin D receptor (VDR).

Retraction: The following article from the Journal of Bone and Mineral Research, “CDP/Cut Is an Osteoblastic Coactivator of the Vitamin D Receptor (VDR)” by Eiji Ochiai, Hirochika Kitagawa, Ichiro Takada, Sally Fujiyama, Shun Sawatsubashi, Mi‐sun Kim,Yoshihiro Mezaki, Yu Tsushima, Ken‐ichiro Takagi, Yoshiaki Azuma, Ken‐ichi Takeyama, Kazuyoshi Yamaoka, Shigeaki Kato, Takashi Kamimura, published online on December 11, 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Thomas Clemens, the American Society for Bone and Mineral Research and Wiley Periodicals, Inc. The authors have requested the retraction based on their acknowledgement that several of the figures did not reflect the observations presented.

Synthesis of 2α-substituted-14-epi-previtamin D3 and its genomic activity

We synthesized and isolated 2 alpha-substituted analogs of 14-epi-previtamin D3 after thermal isomerization at 80 degrees C for the first time. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the 2 alpha-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D3.

Synthesis of 2β-substituted-14-epi-previtamin D3 and testing of its genomic activity ☆

2beta-substituted analogs of 14-epi-previtamin D(3) were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1 nM for transactivation activity, than 14-epi-previtamin D3 with 0.5% (VDR) and EC50 0.46 nM, respectively.