Studies toward the Synthesis of Chartelline C.

Chartelline C, a marine alkaloid, possesses a unique core scaffold including indolenine β-lactam and imidazole moieties linked by an unsaturated 10-membered ring. A new synthetic approach for the construction of the indolenine β-lactam was planned, based on the inherent reactivity of chartelline A with NaOMe, triggered by bromination of bromoenamide, and proceeding through an -acyl imine. However, the -acyl imine intermediate was not observed.

Inhibition of veratridine-induced delayed inactivation of the voltage-sensitive sodium channel by synthetic analogs of crambescin B.

Crambescin B carboxylic acid, a synthetic analog of crambescin B, was recently found to inhibit the voltage-sensitive sodium channels (VSSC) in a cell-based assay using neuroblastoma Neuro 2A cells. In the present study, whole-cell patch-clamp recordings were conducted with three heterologously expressed VSSC subtypes, Na1.2, Na1.

Asymmetric synthesis of crambescin A-C carboxylic acids and their inhibitory activity on voltage-gated sodium channels.

Synthesis of both enantiomers of crambescin B carboxylic acid is described. A cis-enyne starting material was epoxidized under the conditions of Katsuki asymmetric epoxidation to give 95% ee of the epoxide, which was transformed to crambescin B carboxylic acid via bromocation-triggered cascade cyclization as the key step. Enantiomerically pure crambescin A and C carboxylic acids were also synthesized from the product of the cascade reaction.