Arisawa Mitsuhiro
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Chem Pharm Bull (Tokyo). 2007 Aug;55(8):1099-118. doi: 10.1248/cpb.55.1099.
We have developed a novel organometallic catalysis and applied it to drug discovery. Two new catalysts were found, ruthenium hydride with a nitrogen-containing heterocyclic carbene (A) and an organopalladium catalyst supported on a sulfur-terminated semiconductor, gallium arsenide (001) (B). Both catalysts are environmentally benign, because A can yield indole derivatives with good atom economy, and B can catalyze the Mizoroki-Heck reaction more than 10 times with only trace amounts of leached palladium (ppb level). We also describe our synthetic study of nitrogen-containing heterocycles using ring-closing metathesis (RCM), such as chiral bicyclic lactams, azacycloundecenes, axially chiral macrolactams, 1,2-dihydroquinolines and indoles, including the development of silyl-enol ether ene metathesis, selective isomerization of terminal olefin, enamide metathesis and cycloisomerization and its application to the syntheis of 4 natural products, (-)-coniceine, (S)-pyrrolam A, angustureine, and fistulosin.
我们开发了一种新型有机金属催化方法并将其应用于药物发现。发现了两种新催化剂，含氮杂环卡宾氢化钌（A）和负载在硫封端半导体砷化镓（001）上的有机钯催化剂（B）。两种催化剂对环境都无害，因为A能以良好的原子经济性生成吲哚衍生物，而B仅用痕量浸出钯（ppb水平）就能催化Mizoroki-Heck反应十多次。我们还描述了我们使用闭环复分解反应（RCM）对含氮杂环的合成研究，如手性双环内酰胺、氮杂环十一碳烯、轴手性大环内酰胺、1,2-二氢喹啉和吲哚，包括硅烯醇醚烯复分解反应的开发、末端烯烃的选择性异构化、烯酰胺复分解反应和环异构化及其在4种天然产物（-）-coniine、（S）-pyrrolam A、angustureine和fistulosin合成中的应用。
