Microflow synthesis of saccharide nucleoside diphosphate with cross-coupling reactions of monophosphate components

The advantageous features of a split-and-recombination (SAR) microreactor for organic synthesis of labile bioactive compounds are demonstrated with rapid and efficient cross-coupling reactions of two monophosphate components to form a saccharide-nucleoside diphosphate. With this microreactor possessing the SAR mechanism that dramatically enlarges the material interface to promote the fluidic mixing, 85% conversion of a cross-coupling reaction (GlcNAc monophosphate reacting with UMP-morpholidate) to the diphosphate (acetylated UDP-GlcNAc) was achieved in 10 s, which is a small fraction of the two days for 80% conversion with a conventional batch reactor; the duration of reaction is hence decreased 105 fold. Diphosphate from another cross-coupling reaction (GIcNAc monophosphate reacting with phosphoro-p-anisidate) was prepared in 94% yield (HPLC analysis) over a reaction duration 90 s with this microreactor; furthermore, 1 mg of the resulting compound was obtained in similar to 20 min. An abbreviated duration and satisfactory output are expected to be realized when several SAR microreactors are applied in parallel. By means of this microreactor technique, a synthesis with burdensome and protracted procedures becomes facile to generate products with great efficiency. (C) 2012 Elsevier B.V. All rights reserved.