Establishment of novel synthetic strategy utilizing two types of photo-induced direct C(sp3)-H functionalization.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860009
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: NAGATOMO MASANORI 東京大学, 薬学研究科(研究院), 助教 (70634161)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 直截的変換反応 / 全合成 / 光化学反応 / 不斉アルキニル化反応 / ラクタシスチン / 20Sプロテアソーム阻害活性 / ザラゴジン酸C / 高脂血症治療薬

Outline of Final Research Achievements

Development of direct transformations of C-H bonds has attracted intense attention from chemical community. We particularly focus on C(sp3)-H bond oxidations and functionalizations of multiply substituted carboskeletons.
This time we have achieved the following three research results. 　1) Enantioselective alkynylation of C(sp3)-H bonds adjacent to a nitrogen atom has been achieved using only chiral p-tolyl tert-butyldimethylsilylethynyl sulfoximine and benzophenone under photo-irradiation conditions. 2) Total synthesis of (+)-lactacystin, a potent inhibitor of the 20S proteasome has been achieved using the chemo- and stereoselective photoinduced intermolecular C(sp3)-H alkynylation and intramolecular C(sp3)-H acylation. 3) Total synthesis of (+)-zaragozic acid C, having inhibitory activity of mammalian squalene synthase, has been achieved using the chemo- and stereoselective photoinduced intramolecular C(sp3)-H acylation.

Free Research Field

天然物合成化学