Phenethylisoquinoline - derived alkaloids and related systems

The phenethylisoquinoline alkaloids comprise a relatively new class of alkaloids. They are structurally related to the very vast group of alkaloids based on the 1-benzylisoquinoline skeleton. Most of these alkaloids follow a biosynthetic pathway analogous to the benzylisoquinoline series. That is, they are biosynthesized from the 1-phenethylisoquinoline autumnaline (Table 1, A-1) and its relatives by phenolic oxidative coupling and subsequent reactions. At present, nine groups of alkaloids are identified as of the phenethylisoquinoline type (Scheme 1). This includes the simple 1-phenethylisoquinoline (1), homomorphinane (2), colchicine (3), homoproaporphine (4), homoaporphine (5), bisphenethylisoquinoline (6), dibenz[d,fJazecine (7), homoerythrina (8), and cephalotaxine (9) groups. The bold lines in Scheme 1 represent biosynthetic pathways indicated by tracer studies. No tracer studies have been done on those shown with dotted lines. One can see in the Scheme that, biosynthetically, homoerythrina and cephalotaxinemay be related by a common precursor, the dibenz[d,fJazecine-type alkaloid (7). Colchicine on the other hand is derived biosynthetically from a homomorphinane (2), specifically Q-methylandrocymbine (Table 1, C-2). The homoprotoberberine-type alkaloid skeleton (10), which may also be biosynthetically derived from a 1-phenethylisoquinoline precursor by a Mannich-type reaction, and which was anticipated by Battersby to occur in plants, has not yet been isolated. However, a homoprotoberberine (11) was isolated from Berberis acticantha but differs from (10) in the ring C structure. That is, nitrogen and ring D are joined together by an ethylene group in (11) instead of a methylene group as in (10), the latter being characteristic of a Mannich-type ring closure. A complete list of the phenethyli soquinoline-derived alkaloids from plants, their sources, and their physical properties is given in Table 1 and summarised in Table 2. All the isolated alkaloids presented in Kamentani's review are included in Table 1 to provide a better view of the alkaloid profile.