Novel click chemistries for chemical biology researches

2014 Fiscal Year Final Research Report

• Project/Area Number: 24310164
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HOSOYA Takamitsu 東京医科歯科大学, 生体材料工学研究所, 教授 (60273124)
• Co-Investigator(Renkei-kenkyūsha): KII Isao 京都大学, 大学院医学研究科, 特定助教 (80401561)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 化学プローブ / アジド / クリック反応 / アルキン / 化学修飾

Outline of Final Research Achievements

We have developed efficient methods to conjugate functional molecules by sequential triazole formations. One is a modular synthetic method for bis- and tris-1,2,3-triazoles that include a benzotriazole structure, which was developed on the basis of sequential azide-aryne and azide-alkyne cycloadditions. The key to success was efficient halogen-metal exchange reaction-mediated generation of aryne from ortho-iodoaryl triflates bearing a base-sensitive terminal alkyne moiety, which was achieved using trimethylsilylmethyl Grignard reagent. Another is a transient protection method of cyclooctynes from click reaction with an azide through 1:1 complexation with a cationic copper(I) salt. The application of the method to a cyclooctyne bearing a terminal alkyne enabled the selective copper-catalyzed click conjugation with an azide at the terminal alkyne moiety, which made cyclooctyne derivatives readily accessible.

Free Research Field

複合領域