Design and Synthesis of C-1 Methoxycarbonyl Derivative of Narciclasine and Its Biological Activity
Lihi Habaz1, Korey Bedard1, Mitchell Smith2
1Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON L2S 3A1, Canada.
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.
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