Synthesis of Eupolauramine via an Intramolecular Kondrat'eva Pyridine Synthesis

A strategy has been tested for synthesis of annulated pyridines which involves the intramolecular Diels-Alder cycloaddition of an oxazole with an alkene. Oxazole 21 was prepared in four steps from (o-methoxyphenyl)oxazoline 16. Upon heating, 21 produced mixtures of two tricyclic hydroxypyridines 23 and 24 in good total yield. Thermolysis of 21 in the presence of DBN changed the course of the reaction, leading to the desired tricyclic pyridine 25. Two short routes have been developed for conversion of 25 to the structurally unique azaphenanthrene alkaloid eupolauramine (6a). The first sequence involved intermediate azaphenanthrene-o-quinone 30 and hydroxy lactam 31 (Scheme IV). A more efficient route from 25 utilized the azaarene epoxide 33, which was converted via lactam alcohol 34a to eupolauramine.