Asymmetric synthesis and biological activities of natural product (+)-balasubramide and its derivatives

Methyl (2S,3R)-(+)-3-phenyloxirane-2-carboxylate ( 1h ), the asymmetric synthesis of which was described in a previous paper, was selected as the starting material. Compounds 3a–3j were evaluated for their neuroprotective, antioxidative, and anti-neuroinflammatory effects.

(+)-Balasubramide and its derivatives with different electronegative groups in the 6-phenyl ring produced little neuroprotection and antioxidation, but induced potent anti-neuroinflammatory effects in BV-2 microglial cells (with the exception of 3g) . Compound 3c , with a trifluoromethyl group in its 6-phenyl ring, was a particularly potent anti-neuroinflammatory agent. These results demonstrated that the electronegativity of the 6-phenyl ring of (+)-balasubramide is an important determinant of its inhibitory effect on neuroinflammation.