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

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.