Pseudopterosin A

Due to their pronounced bioactivity and limited availability from natural resources, metabolites of the soft coral Pseudopterogorgia elisabethae, such as erogorgiaene and the pseudopterosines, represent important target molecules for chemical synthesis. We have now developed a particularly short and efficient route towards these marine diterpenes exploiting an operationally convenient enantioselective cobalt‐catalyzed hydrovinylation as the chirogenic step. Other noteworthy C−C bond forming transformations include diastereoselective Lewis acid‐mediated cyclizations, a Suzuki coupling and a carbonyl ene reaction. Starting from 4‐methyl‐styrene the anti‐tubercular agent (+)‐erogorgiaene (>98 % ee) was prepared in only 7 steps with 46 % overall yield. In addition, the synthesis of the pseudopterosin A aglycone was achieved in 12 steps with 30 % overall yield and, surprisingly, was found to exhibit a similar anti‐inflammatory activity (inhibition of LPS‐induced NF‐κB activation) as a natural mixture of pseudopterosins A−D or iso‐pseudopterosin A, prepared by β‐D‐xylosylation of the synthetic aglycone.

Brain injury caused by ischaemic stroke is a major cause of disability and death throughout the world. The present study evaluates the neuroprotective effect of pseudopterosin A (PtA) against ischaemia-induced brain injury.

Ischaemia was induced by pMCAO model, and rats were separated in to three groups. A control group; an ischemic group receiving saline solution; and a PtA group receiving PtA (5 mg/kg, i.p.) for the period of three days, i.e. two days before surgery and after the surgery. Effect of PtA was assessed by estimating the infract volume and neurological deficits. Level of oxidative stress, inflammatory mediators, and markers of apoptosis were estimated in the brain tissues. Western blot assay and immunohistochemistry was done for the assessment of expressions of protein.

Data from the study suggest that treatment with PtA significantly decreases the infracted volume and neurological deficit score compared to the ischaemic group. Treatments with PtA attenuate the activity of antioxidant enzyme, and the level of inflammatory mediators and markers of apoptosis in the brain tissues of ischaemia-induced brain injury. Phosphorylation of FKHR, Bad, and Akt were significantly reduced in the PtA-treated group compared to the ischaemic group.

The present study shows that pseudopterosin A attenuates neuronal injury in the pMCAO model by acting on the Akt signalling pathway.