Mitosene analogs

Edstrom has utilized the carbonylation variation to engineer new routes to 3-substituted 4-hydroxyindoles, indolequinones, and mitosene analogs [113, 114]. For example, triflate 155 is converted to methyl ester 156 in high yield [114]. Subsequent oxidation affords indole 157. 

It has been known for sometime that 2-(2-bromoanilino)enones undergo Heck-type cyclizations to form indoles and carbazoles. Thus, Kibayashi reported the synthesis of 4-keto-l,2,3,4-tetrahydrocarbazoles in this manner [362], and Rapoport employed this reaction (296 to 297) to achieve an improved synthesis of 7-methoxymitosene [363]. A series of related mitosene analogs has been crafted using Pd chemistry by Michael and co-workers [364], They found that P(o-tol)3 was far superior to PPh3 in conjunction with Pd(OAc)2. 

Alkylation reactions by the iminium methide species are well known in the mitomycin and mitosene literature 4,49,51-53 and are largely responsible for the cytotoxicity/antitumor activity of these compounds. As illustrated in Scheme 7.8, the electron-rich hydroquinone intermediate can also be attacked by the iminium ion resulting in either head-to-head or head-to-tail coupling. The head-to-head coupling illustrated in Scheme 7.8 is followed by a loss of formaldehyde to afford the coupled hydroquinone species that oxidizes to the head-to-head dimer upon aerobic workup. Analogous dimerization processes have been documented in the indole literature, 54-56 while the head-to-tail mechanism is unreported. In order to... 

Several extended pyrazoloquinones were prepared either as analogs of mitosenes (84LA1711) or from studies of various sydnones and quinones (65JCS5871). 

The syntheses described below afforded pyrrolo[l,2-a]indoles that are not direct precursors to mitosenes. Nevertheless, they are important because they contain strategies or techniques that might be valuable to subsequent preparations of mitomycin analogs. 

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