Sulfur and azobenzenes, a profitable liaison: straightforward synthesis of photoswitchable thioglycosides with tunable properties

Azobenzene photoswitches are valuable tools for controlling properties of molecular systems with light. In particular, we have been investigating azobenzene glycoconjugates to probe carbohydrate-protein interactions and also to design photoresponsive glycomacrocycles with modulable chiroptical and physicochemical properties. To date, direct conjugation of glycosides to azobenzenes was performed by reactions providing target compounds in limited yields. We therefore sought for a more effective and reliable coupling method. In this paper, we report on a straightforward thioarylation of azobenzene derivatives with glycosyl thiols as well as other thiol substrates, increasing the scope of azobenzene conjugation. Importantly, red-shifted azoswitches that can be addressed with visible light were easily functionalized and challenging unsymmetrical conjugates were prepared in good yields via sequential or one pot procedures. In addition, we took advantage of the presence of the sulfide bridge to tune both photochromic and thermal relaxation properties of the core azobenzene via sulfur oxidation. Based on our photochemical investigations, we finally demonstrated orthogonal three-state photoswitching in mixtures containing two distinct azobenzene thioglycosides.