Enzymatic Synthesis of a Series of Thioglycosides: Analogs of Arbutin with Efficient Antipigmentation Properties

Arbutin, a natural glycoside, is well known as a commercial tyrosinase inhibitor, and thus, to prevent pigmentary disorders of skin. In fact, tyrosinase is involved in the biosynthesis of melanin, the skin main pigment. However, arbutin is subject to hydrolysis, which limits its bioactivity. In general, thioglycosides are known to be very resistant to both chemical and enzymatic hydrolysis, which increases the interaction time with their biological targets. A biocatalytic approach allowed us to access to thioglycosidic analogs of arbutin in a green approach with good to excellent yields. Such compounds have then been tested as tyrosinase inhibitors as well as inhibitors of melanin transfer from melanocytes to keratinocytes. This latter mechanism takes place via lectin (or lectin-like) receptors present on the cells surface. p-Aminophenyl beta-D-thiogalactopyranoside appears to be an excellent candidate thanks to its tyrosinase inhibitory activity comparable to arbutin, while having the ability to interact with glycan receptors allowing to reduce melanin transfer.