The trimethylsilyl trifluommethanesulfonate accelerated Diels-Alder reaction between 1,3-dimethyl-4-(phenylsulfonyl)-4H-foro[3,4-b]indole (3) and 5,6-dihydropyridones (10) shows high regioselectivity, yielding carbazole 17 upon hydrolytic workup. Carbazole 77b has been successfully converted to the pyridocarbazole alkaloid ellipticine (1).
The pyrido[4,3-blcarbazole alkaloid ellipticine (1) exhibits pronounced anticancer activity in several animal and human systems2 and a derivative, 2-methyl-9-hydroxyellipticinium acetate ("elliptinium", 2). is a clinically proven drug for the treatment of metastatic breast cancer, myeloblastic leukemia, and some solid tumors.3
Because of its great biological activity, ellipticine has been the target of many synthetic endeavors.4
In 1984. we reported a novel synthesis of ellipticine via a Diels-Alder reaction between 1.3~dimethyl-4-(phenylsulfonyl)-4H-furo[3,4-blindole (3) and 3,4-pyridyne (4).5 Unfortunately, this reaction showed little or no regioselectivity and thus "isoellipticine" (5) was also a major product. Moody has also shown that pyridyne 4 undergoes a nonregioselective cycloaddition reaction with 1,4-dimethylpyrano[3,Cb]indole, producing a 1:l mixture of 1 and 5 in 40% combined yield.6