Synthetic study of highly strained anti-cancer natural products by way of umpolung strategy using reactive chemical species

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K17856
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Synthetic chemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Tanimoto Hiroki 奈良先端科学技術大学院大学, 物質創成科学研究科, 助教 (00581331)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ニトロソ / 極性転換 / アレン / 環化反応 / ニトロン / オキシム

Outline of Final Research Achievements

First synthesis of nitrosoallenes showing highly strong reactivity was accomplished, and their characters on the reactions with various nucleophiles were also researched. These reactive species achieved umpolung substitutions compared to general chemical characters, which gave unsaturated oximes with alpha-substitution with nucleophiles. These reactions accepted various nucleophiles such as amines, alcohols, thiols, and carbon nucleophiles like enolates and cyanide. With enolates, highly complexed cyclic nitrones were produced. Toward application to synthesis of anti-cancer natural products, intramolecular cyclization reactions were also examined. Not only C-N bond, but also C-S, C-O, and C-C bond formations were successfully achieved to afford cyclic enoximes with formation of all-carbon quaternary centers. Our results revealed the efficiency of the nitrosoallene species in endo-type cyclizations to form hetero- and carbocycles toward strain skeletons in bioactive natural products.

Free Research Field

有機合成化学