Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity

Abstract

A 15-step chemoenzymatic total synthesis of C-1 methoxycarbonyl narciclasine (10) was accomplished. The synthesis began with the toluene dioxygenase-mediated dihydroxylation of ortho-dibromobenzene to provide the corresponding cis-dihydrodiol (12) as a single enantiomer. Further key steps included a nitroso Diels–Alder reaction and an intramolecular Heck cyclization. The C-1 homolog 10 was tested and evaluated for antiproliferative activity against natural narciclasine (1) as the positive control. Experimental and spectral data are reported for all novel compounds.

Keywords

• narciclasine
• chemoenzymatic
• synthesis
• enantioselective synthesis
• natural products
• toluene dioxygenase