A new precursor to 3,4-didehydropyridine, and its use in the synthesis of the antitumour alkaloid ellipticine

Abstract

A concise synthesis of the antitumour alkaloid ellipticine (1) is reported. The route involves a Diels-Alder reaction between 1,4-dimethylpyrano[3,4-b] indol-3-one (3), easily prepared in two steps from indole, and 3,4-didehydropyridine (4), and for its successful execution required the development of a new thermal, reagent-free precursor to the aryne. This precursor, 3-(3,3-dimethyltriazen-1-yl)pyridine-4-carboxylic acid (10a), prepared from 3-aminopyridine-4-carboxylic acid, decomposes in boiling acetonitrile to generate 3,4-didehydropyridine which can be intercepted in Diels-Alder reactions with tetraphenylcyclopentadienone, furan, and 2,5-dimethylfuran. The triazenes (10b) and (10c) can be prepared and decomposed similarly. The key Diels-Alder reaction between the pyranoindolone (3) and 3,4-didehydropyridine (4) gives ellipticine (1) in 20% yield, together with an equal amount of isoellipticine (14).