Pyridocarbazole alkaloids

A further extension of this strategy has been employed as a route to carbazoles, as illustrated by the synthesis of the system 116 from the 2-nitrobiphenyl derivative 117 (Equation 30) <20040L533>. A substituted 2-nitrobiphenyl derivative has been cyclized to a carbazole using P(OEt)3 en route to the pyridocarbazole alkaloid ellipticine <2006HCA111>. It should also be mentioned that annulation of o-(alkynyl)nitrobenzene precursors with TBAF or pyridine gave access to indol-3-one-l-oxides (isatogens) <2003T2497>. 

Kozikowski and Hasan (77JOC2039) used an intermolecular Diels-Alder reaction for the synthesis of the pyridocarbazole alkaloid ellipticine (456) (Scheme 57). Reaction of oxazolediene 454 with excess acetic acid at 145°C gave the pyridine 455 in 16% yield. Addition of methyllithium to cyanopy-ridine 455 followed by hydrolysis and cyclization with acetic acid afforded ellipticine (456). 

Carbon-carbon bond formation by intramolecular cyclization of conjugated iminium ions is also possible, as illustrated by the transformation of amine oxide (36) to (37), a key intermediate in the synthesis of the pyridocarbazole alkaloid ellipticine (38 Scheme 7). ... 

Joule and co-workers ° have described the synthesis of the pyridocarbazole (192) and derivatives containing a partially-reduced ring d, which are potential intermediates in the synthesis of the rare alkaloid subincanine, whose structure has not yet been unambiguously defined. 

It has been reported that the furoindole (361) underwent Diels-Alder reactions with DMAD, N-phenylmaleimide and benzyne to give the expected products <84JOC45l8>. Treatment of 3-chloro-4-iodo-pyridine with t-butyllithium followed by addition of (361) led to a mixture of the isomeric Diels-Alder adducts (362) and (363) in 15% yield. Deoxygenation and desulfonylation of (362) and (363), gave a readily separable mixture of the pyridocarbazole alkaloids ellipticine (364), and isoellipticine (365), respectively (Scheme 14) <84JOC45l8,83TL5435>. 

Details of the synthesis of ellipticine and related pyridocarbazole alkaloids by Gilbert et al. have now been published. "... 

Pyridocarbazole alkaloids, 21 Pyridon, 109, 127 Pyridone, 142, 143 Pyridon quinolizidine alkaloids, 141 Pyridostigmine, 158 Pyridoxal phosphate, 116 Pyriferines A-C, 65-67 Pyrolidines, 8... 

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