Desulfohaplosamate, a new phosphate-containing steroid from Dasychalina sp., is a selective cannabinoid CB2 receptor ligand

From the polar organic extract of the Indonesian sponge Dasychalina sp. we have isolated haplosamate A (1), a unique C-28 sterol containing a sulfate group at C-3 and a methyl phosphate at C-15, along with its new desulfo analogue 2, whose structure has been secured by detailed NMR investigation. Compounds 1 and 2, as well as their semi-synthetic analogues 3-5, have been evaluated for interaction with CB1 and CB2 receptors through a binding test. Desulfohaplosamate (2) showed a selective affinity for CB2 receptors in the low mu M range, while a semi-synthetic derivative with cleaved ring B showed a complete loss of affinity for both receptors, highlighting the importance of an intact steroid nucleus. To our knowledge, haplosamate derivatives represent the first CB receptor ligands belonging to the class of steroids. (C) 2011 Elsevier Inc. All rights reserved.