A simple polar deacetylated caloporoside derivative is a positive modulator of the GABAA chloride channel complex in cortical mammalian neurones

Synthesis of octyl-O-β- -mannopyranoside, a caloporoside analogue was achieved by the activation of 2,3,4,6-tetra-O-benzyl-1-O-1′,3′2′-dioxaphosphacyclohexane-α,β- -mannopyranosyl-2-oxide with TMSOTf (Trimethyl silyl triflate) and subsequent debenzylation. At 100 μM the molecule significantly and reversibly increased the magnitude of GABAA currents evoked in cultured rat pyramidal neurones whilst concomitantly reducing the incidence of spontaneous synaptic activity. These results contradict earlier proposals that such molecules bind to the TBPS (tert-Butylbicyclophosphorothionate) site to block the chloride channel.