Chemo-enzymatic synthesis of benzoylated hexapyranosides and derivatives

Conjugation of glucuronic acid to polar anchor groups such as hydroxy- and amino-groups are considered as a fundamental mechanism in nature for detoxifying and elimination lipophilic waste chemicals from the body (1). The most versatile synthetic route to glycosylation products is still the classical Koenigs-Knorr reaction (2) and is extensively used for O-glucuronidation. However, synthesis N+- glucuronides, is generally more difficult. Using the antiepileptic drug lamotrigine, we have demonstrated a new synthetic route to N+-glucuronides in previously unprecedented yields. In order to produce a range of different uronic acids, access to partially acylated pyranosides with a free C6 hydroxy group was needed. This was achieved in good yields by regioselective hydrolysis of the corresponding tetrabenzoyl pyranosides using Candida rugosa lipase. On the course to fluorinated analytical standards, the deprotected benzoyl pyranosides was subjected to fluorinating agents (DAST and BAST), producing a range of fluorinated pyranosides.