In 1992 and 1993, (–)-conophylline and (–)-conophyllidine were isolated from Tabemaemontana divaricata in 0.065% and 0.0043% yield, respectively by Kam and coworkers. In 2010, (–)-melodinine K, which is in the same family (bis-aspidosperma alkaloids) and has similar structure to (–)-conophyllidine and (–)-conophylline, was isolated from Melodinus tenuicaudatus by Luo and coworkers (&lt;0.006%). These molecules have been shown to possess anti-cancer properties against several cancer cell lines. Especially, (–)-conophylline and (–)-conophyllidine are capable of inducing β-cell differentiation, a potential therapy for type 1 diabetes mellitus. Due to their biological importance and low yield by isolation, chemical syntheses of these molecules have been explored ever since. From a less complex scaffold (–)-melodinine K, novel chemistry methods can be applied to synthesize and investigate more biologically active and synthetically challenging analogs. The procedure of synthesizing the molecule included the critical Polonovski-Potier coupling of 16-allyloxytabersonine and N-troc pachysiphine. Both fragments were derived from (–)-tabersonine, which was isolated from Voacanga africana (ground beans found in Africa). (–)-Tabersonine was oxidized selectively at the 16th position to obtain 16-hydroxytabersonine fragment by exploiting the yeast strain Watt11 containing the plasmid pYeDP60, which has the gene tabersonine 16 hydroxylase (T16H2). The other fragment N-troc pachysiphine was prepared by chemical synthesis with (–)-tabersonine as the starting material. Recently, we have successfully synthesized (–)-melodinine K and been testing for its biological activity.

Semi-synthesis of (–)-melodinine K via chemical and biological routes

2019 Spring National Meeting

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