A methods development approach towards the Galanthan skeleton starting with isoquinoline

Abstract

The preparation of the galanthan skeleton was achieved in 7 steps with a 35% overall yield from isocarbostyril. The crucial step in this process involved the first reported intramolecular de Mayo reaction of an isocarbostyril substrate. The first intermolecular de Mayo reaction of an isocarbostyril is also depicted. A simple and inexpensive method for the preparation of isocarbostyril from isoquinoline was developed. This method utilized the straightforward and efficient cleavage of the N-vinyl amide group with a relatively mild acidic solution at ambient temperature. A brief examination of the reactivity of isocarbostyril substrates in the intramolecular Diels-Alder reaction is also reported. Work utilizing this method as the key step in producing the galanthan skeleton proved unsuccessful but inspired a number of intriguing questions and established the basis for a number of interesting research projects.