Mitosene, synthesis

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. 

Michael et al. <2001TL7513> described a Heck cyclization of 154 to form functionalized mitosene 155 which was further transformed into tetracyclic compound (route b). Also Lee et al. <1999JOC4224> described a synthesis in... 

Scheme 13. Indole radical intermediacy in the total synthesis of a mitosene...

An efficient and economical new approach toward the synthesis of 7-aminoaziridinomitosenes, as represented by compound 96, has been developed in less than 15 total operations from commercially available chemicals. Overall our scheme represents the second total synthesis of a fully functionalized aziridinomitosene. At one stage, new insights into the mechanistic details involving the reaction of l,2-epoxypyrrolo[l,2-c]indoles with nucleophiles are provided. Notably, the route presented has the advantage of accessing both the aziridine and 7-amino substituents in deprotected form. Further application of this synthetic approach to additional C-9-substituted mitosenes can be anticipated. 

Intramolecular radical addition to isolated unsaturated bonds in the synthesis of pyrroloindoles - a ring system found in the biologically active mitosenes has been studied in detail (95TL4857), (98T2149) (Scheme 25). 

Jones GB, Moody CJ (1989) Structurally modified antitumor agents. Part 1. Synthesis of cyclopropapyrrolo[l,2-a]indoles related to mitosenes by intramolecular cycloaddition. J Chem Soc Perkin Trans 1 2449-2454... 

Kusama H, Miyashita Y et al (2006) Pt(II)- or Au(III)-catalyzed [3+2] cycloaddition of metal-containing azomethine ylides highly efficient synthesis of the mitosene skeleton. Org Lett 8 289-292... 

Orlemans EOM (1988) Synthesis of Mitosenes and Isomitosanes, Dissertation, Twente Univ of Technology, Enschede, The Netherlands... 

Iwasima and colleagues engineered the Pt-catalyzed [3h-2] cycloaddition of A-(<9-alkynylphenyl)imines with activated alkenes into a synthesis of the mitosene skeleton (Scheme 2, equation 1) [6]. The gold catalyst, AuBrj, is equally effective. Nakamura s group described a novel Pt-catalyzed dehydroalkoxylation/cyclization cascade process... 

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