Continuous synthesis of pyridocarbazoles and initial photophysical and bioprobe characterization

Pyridocarbazoles when ligated to transition metals yield high affinity kinase inhibitors. While batch photocyclizations enable the synthesis of these heterocycles, the non-oxidative Mallory reaction only provides modest yields and difficult to purify mixtures. We demonstrate here that a flow-based Mallory cyclization provides superior results and enables observation of a clear isobestic point. The flow method allowed us to rapidly synthesize ten pyridocarbazoles and for the first time to document their interesting photophysical attributes. Preliminary characterization reveals that these molecules might be a new class of fluorescent bioprobe

光と酸素或いは過酸化水素を用いる酸化反応の開発に関する研究

酸化反応は有機合成上有用な反応であるが、従来の手法では毒性の高い重金属酸化剤や原子効率の低い複雑な有機分子が必要であった。一方、分子状酸素や過酸化水素を末端酸化剤とする手法は、原子効率が高く、廃棄物として理論上水のみを排出する、グリーンケミストリーの概念に合致した酸化法である。筆者らは最終酸化剤としての「過酸化水素」ならびに「分子状酸素」を利用した環境負荷低減を指向した酸化反応の開発を行った。その結果、ハロゲンソース存在下、スチレン類の光酸素酸化により、対応するフェナシルハライド類を合成することに成功した。また、光酸素酸化反応の後に単体ヨウ素を触媒とする反応をワンポットで行うことにより、スチレン類からアセトフェノン類を、ベンジルアルコール類からビスインドリルメタン類をそれぞれ合成することに成功した。さらに、単体ヨウ素存在下、酸化剤として過酸化水素或いは分子上酸素を用いることにより、三級アミン類と炭素求核剤の酸化的カップリング反応にも成功した。Oxidation is one of the most important reactions in organic synthesis; however, classical methods require toxic heavymetal reagents or complex organic molecules. On the other hand, oxidation using oxygen or hydrogen peroxide has received muchattention in organic synthesis recently since these reagents are effective oxidants of larger atom efficiency and theoretically produceonly water as the end product. With this perspective, we have studied oxidation using oxygen or hydrogen peroxide as a terminaloxidant. As a result, we found that styrenes can be oxidized to corresponding phenacylhalides under aerobic photo-oxidativeconditions in the presence of halogen sources. We also developed one-pot synthesis of acetophenones and bis-indolylmethanes fromstyrenes and benzylalcohols, which includes aerobic photo-oxidation followed by iodine catalyzed reaction, respectively.Furthermore, we developed a cross-dehydrogenative coupling reaction between tertiary amines and carbon nucleophiles usinghydrogen peroxide or oxygen as a terminal oxidant in the presence of catalytic iodine

Molecular Iodine Catalyzed Cross-Dehydrogenative Coupling Reaction between Two sp³ C–H Bonds Using Hydrogen Peroxide

A useful method for molecular iodine catalyzed oxidative C–C bond formation between tertiary amines and a carbon nucleophile using hydrogen peroxide as the terminal oxidant is reported. This is the first report of a molecular iodine catalyzed cross-dehydrogenative coupling (CDC) reaction between two sp³ C–H bonds

Ambient Temperature Is Correlated With the Severity of Neonatal Hypoxic-Ischemic Brain Injury via Microglial Accumulation in Mice.

Background:The pathophysiology of neonatal hypoxic-ischemic encephalopathy (HIE) has been studied in several rodent models to develop novel treatments. Although it is well known that high ambient temperature results in severe HIE, the effect of subtle changes in ambient temperature during a hypoxic-ischemic (HI) insult has not been studied. Therefore, in order to clarify the difference of pathophysiological change among the HIE models due to the influence of small changes in chamber temperature, three-step gradual change of 0.5°C each were prepared in ambient temperature during hypoxic exposure.Methods:Blood flow in the left common carotid artery (CCA) of neonatal mice was interrupted using bipolar electronic forceps under general and local anesthesia. The mice were subsequently subjected to 10% hypoxic exposure for 50 min at 36.0, 36.5, or 37.0°C. A control group was also included in the study. The size of the striatum and hippocampus and the volume reduction rate of the hemisphere in the section containing them on the ischemic side were evaluated using microtubule associated protein 2 (MAP2) immunostaining. The accumulation of Iba1-positive cells was investigated to assess inflammation. Additionally, rotarod and open-field tests were performed 2 weeks after HI insult to assess its effect on physiological conditions.Results:MAP2 staining revealed that the higher the temperature during hypoxia, the more severe the volume reduction rate in the hemisphere, striatum, and hippocampus. The number of Iba1-positive cells in the ipsilateral lesion gradually increased with increasing temperature, and there was a significant difference in motor function in the 36.5 and 37.0°C groups compared with the sham group. In the open-field tests, there was a significant decrease in performance in the 37.0°C groups compared with the 36.0°C and sham groups.Conclusions:Even a small gradual change of 0.5°C produced a significant difference in pathological and behavioral changes and contributed to the accumulation of Iba1-positive cells. The arrangement of ambient temperature is useful for creating a rodent model with the appropriate severity of the targeted neuropsychological symptoms to establish a novel therapy for HIE