The synthesis of complex carbohydrates still remains a challenge, despite the enormous progresses achieved in synthetic organic chemistry during the last two decades. The general efficiency of saccharide blocks assembly depends indeed on different parameters. First, the monosaccharide residues needed for the preparation of larger saccharide structures often require multistep synthesis with laborious protecting groups manipulations. In addition, a general experimental protocol able to ensure high-yielding and stereoselective glycosylations using diverse glycosyl donors and acceptors is still missing. The identification of the most suitable reaction conditions is time-consuming and may lead to massive waste of precious synthetic intermediates. Last but not least, optimization and subsequent scale-up pose an additional hurdle. Continous-flow microfluidic devices offer a well-engineered approach to meet some of these challenges, especially in terms of fine tuning of the reaction parameters.
Quite surprisingly, glycosylation reactions have been still little explored under continous-flow conditions, and only few examples of this chemistry are reported in literature.1
In this communication we report our investigation on the use of microfluidic reactor in carbohydrate chemistry area, with particular emphasis on the glycosylation reactions.
Initially, a panel of glycosyl acceptors and two of the most used glycosyl donors with non participating neighbouring groups at C-2 were synthesized to be employed in glycosylation reactions (Scheme 1).
Noteworthy, glycosylations performed under flow conditions proceeded smoothly at room temperature and with no need of inert atmosphere nor molecular sieves, giving good results in terms of yield (up to 99%) and without significant changes of stereoselectivity in comparison to traditional conditions.
Finally, the first example of two-consecutive steps (donor synthesis and subsequent glycosylation) performed into a microreactor will be described.
1 (a) Chem. Comm. 2005, 578; (b) Helv. Chim. Acta 2007, 90, 395; (c) Beilstein Journal of Organic Chemistry 2009, 5, 40
