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 C28 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 μM 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.

Figure optionsDownload as PowerPoint slideHighlights
► Desulfohaplosamate (2), the fourth member of the haplosamate group of phosphate-containing steroids, was isolated from Dasychalina sp.
► Desulfohaplosamate showed a selective affinity for CB2 receptors.
► The semisynthetic dialdehyde derivative 3 showed a complete loss of affinity for CB1 and CB2, highlighting the importance of an intact steroid nucleus.
► Haplosamate derivatives are the first CB agonists belonging to the class of steroids.