Hiromi Nishioka

Novel Synthesis of Benzoxazoles from O-Nitrophenols and Amines

o-Nitrophenols and o-nitroaniline were reacted with amines at 210-215°C to produce the corresponding benzoxazoles and benzimidazoles, respectively, in moderate yields. The reactions between o-nitrophenols containing a CO 2 Me or OMe group on their benzene rings and N,N-diethylaniline were examined to investigate the effects of the position and electronic character of these substituents on the formation of the oxazole ring.

Intramolecular Pd-catalyzed biaryl coupling reaction of N-aryl-2-triflyloxybenzamides using Pd(OAc)2, 1,3-bis[diphenylphosphino]propane, Bu3P, and DBU

Intramolecular Pd-catalyzed coupling reactions of N-aryl-2-triflyloxybenzamides were examined. The procedure using DBU as a base was effective for even in the reaction of oxygen-substituted benzamides.

Synthesis of febrifugine derivatives and a solution to the puzzle of the structural determination of febrifugine

The stereo-structure of piperidine lactone (3), a synthetic intermediate of the antimalarial agent febrifugine ((+)-1) with a piperidine ring in the trans relative configuration, was re-revised to the cis-form. We determined that isomerization to the trans-form from the cis-form occurred in the stage (6 from 5) of deprotection in Bakers synthesis.

Structure-activity relationship of indoloquinoline analogs anti-MRSA.

Indolo[3,2-b]quinoline analogs (3a-3s), 4-(acridin-9-ylamino) phenol hydrochloride (4), benzofuro[3,2-b]quinoline (3t), indeno[1,2-b]quinolines (3u and 3v) have been synthesized. Those compounds were found to exhibit anti-bacterial activity towards Methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship studies were conducted that indoloquinoline ring, benzofuroquinoline ring and 4-aminophenol group are essential structure for anti-MRSA activity.

Synthesis of 11C-Labeled RXR Partial Agonist 1-[(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic Acid (CBt-PMN) by Direct [11C]Carbon Dioxide Fixation via Organolithiation of Trialkyltin Precursor and PET Imaging Thereof

The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimers and Parkinsons diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([11C]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1. We found that 11CO2 fixation after tin-lithium exchange at -20 °C afforded [11C]1. This methodology may also be useful for synthesizing 11CO2H-PET tracer derivatives of other compounds bearing π-rich heterocyclic rings. A PET/CT imaging study of [11C]1 in mice indicated 1 is distributed to the brain and is thus a candidate for treatment of CNS diseases.