Practical syntheses of 4-fluoroprolines

4-Fluoroprolines are among the most useful nonnatural amino acids in chemical biology. Here, practical routes are reported for the synthesis of the 2S,4R, 2S,4S, and 2R,4S diastereomers of 4-fluoroproline. Each route starts with (2S,4R)-4-hydroxyproline, which is a prevalent component of collagen and hence readily available, and uses a fluoride salt to install the fluoro group. Hence, the routes provide process-scale access to these useful nonnatural amino acids.

Graphical abstractRoutes have been developed for the economical, process-scale synthesis of the 2S,4R, 2S,4S, and 2R,4S diastereomers of 4-fluoroproline.Figure optionsDownload full-size imageDownload as PowerPoint slide