Systematic Strategy for the Development of Glycosyltransferase Inhibitors: Diversity-Oriented Synthesis of FUT8 Inhibitors

Glycans control various biological processes, depending on their structures. Particularly, core fucose, formed by alpha 1,6-fucosyltrans-ferase (FUT8), has a substantial influence on multiple biological processes. In this study, we investigated the development of FUT8 inhibitors with structural elements encompassing both the glycosyl donor(GDP-fucose) and acceptor (N-glycan) of FUT8. To efficiently optimize the structure of FUT8 inhibitors, we employed a strategy involving frag-mentation of the target structure, followed by a structure optimization using a diversity-oriented synthesis approach. This study proposes an efficient strategy to accelerate the structural optimization of middle molecules.