Mitomycins and Related Natural Products

Another alkylating drug in clinical use is mitomycin C. As a natural product isolated from Stremtomyces lavendulae, mytomycin C is an aziridine compound, which is closely related to nitrogen mustards. This compound is best known to the DNA repair field as a DNA interstrand crosslinking agent. Mytomycin C has been used to treat breast cancer and cancers of the gastrointestinal tract. 

Ciufolini and co-workers demonstrated the use of 1,3-dipolar azide-olefin cycloaddition reactions in the total synthesis of ( )-FR66979 (52) [25], an antitiunor agent which is structurally related to the mitomycins [26]. Thus, the triazoline 50 was obtained as a single diastereomer by smooth cycloaddition of the activated double bond and the dipole in 49 by heating in toluene. Brief photolysis of 50 provided aziridine 51, which fragmented to 52 (Scheme 8B). Other intramolecular azide-alkene cycloaddition in natural product synthesis is illustrated by a munber of examples [27-32]. 

Related Reagents. Several other 2-trialkylsilyloxyfurans have served as building blocks for the synthesis of natural products and analogs. The commercially available (4-methoxy-2-(trime-thylsilyloxy)furan (3) is especially useful for preparing 5-substit-uted methyl tetronates. 5-Ethylthio-2-(trimethylsilyloxy)furan (4)2ia employed for the synthesis of mitomycins. The... 

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