Synthesis of a suite of click-compatible sugar analogs for probing carbohydrate metabolism

Metabolic labeling based on the click chemistry between alkynyl and azido groups offers a powerful tool to study the function of carbohydrates in living systems, including plants. Herein, we describe the chemical synthesis of six alkynyl-modified sugars designed as analogs to D-glucose, D-mannose, L-rhamnose and sucrose present in plant cell walls. Among these new alkynyl probes, four of them are the 6-deoxy-alkynyl analogs of the corresponding sugars and do not possess any 6-OH groups. The other two are based on a new structural design, in which an ethynyl group is incorporated at the C-6 position of the sugar and the 6-OH group remains. The synthetic routes for both types of probes share common aldehyde intermediates, which are derived from the corresponding 6-OH precursor with other hydroxy groups protected. The overall synthesis sequence of these probes is efficient, concise, and scalable.