First Total Synthesis of a Fluorinated Calystegin

Calystegins [1] are bicyclic alkaloids that hold structural features derived from the nortropane skeleton; they are poly-hydroxylated and represent a group of plant secondary metabolites with structural closeness to sugars. Like iminosugars they display strong and/or specific competitive inhibitory activity [2 – 4], and they have been suggested as chemotherapeutic drugs to treat viral diseases [5, 6] and metabolic disorders [7, 8] (e. g. diabetes); quite recently, they have been suggested [9] as pharmacoperones for the treatment of protein folding disorders. Naturally occurring calystegins have been obtained from their natural sources [1] by more or less tedious extraction processes; only a few of them have become available by total synthesis [10 – 22]. No functional derivatives of calystegins have been prepared so far.