Phenethylisoquinoline alkaloids colchicine

Phenethylisoquinoline alkaloids are classified into six major alkaloid groups based on structural differences, namely, simple 1-phenethyliso-quinoline (1), homomorphinandienone (2), bisphenethylisoquinoline (3), homoproaporphine (4), homoaporphine (5), and homoerythrina alkaloids (6). These alkaloids are related to the benzylisoquinoline alkaloids such as morphinandienone, bisbenzylisoquinoline, proaporphine, apor-phine, and erythrina alkaloids. Although colchicine and its derivatives also belong to the phenethylisoquinoline alkaloids group, these alkaloids are not included in this review as they have been reviewed earlier 1). 

Alkaloids are not limited to those natural products which are basic in character. For example, colchicine isolated from Colchicum autumnale (Ldiaceae) and used for the treatment of gout, etc. is not basic because the nitrogen atom in the molecule is present in a neutral amide group. However, the biosynthetic precursor of colchicine is autumnaline, a typical, basic phenethylisoquinoline alkaloid. Therefore any compound derived from such an intermediate should be classified as an alkaloid. 

Autumnaline is a phenethylisoquinoline alkaloid, and possesses an additional Cj unit compared with the benzylisoquinoline alkaloids. Autumnaline, postulated to be the biosynthetic precursor of colchicine, was isolated from Colchicum cornigerutn (Colchicaceae) [4]. O-methylandrocymbine is formed through the intramolecular -oxidative phenolic coupling... 

Phenethylisoquinoline alkaloids constitute another important group of tyrosine-derived secondary metabolites. This class of natural products with colchicine (54) as most prominent member is obtained when aldehyde 43 is employed in a condensation reaction with dopamine, followed by a Pictet-Spengler cyclization reaction. The difference to benzyltetrahydroisoquinoline alkaloids is an additional carbon between the tetrahydroisoquinoline core and the aromatic ring. As outlined in Scheme 12.9, aldehyde 43 is derived from phenylalanine (42) via intermediary formation of 4-hydroxycinnamaldehyde. The formation of the tetrahydroisoquinoline system 44 from dopamine (4) and 4-hydroxydihydrocinnamaldehyde (43) is followed... 

Several genera of the Liliaceae plant family have been identified to produce the secondary metabolite autumnaline (45), which also serves as key intermediate in the biosynthesis of a variety of phenethylisoquinoline alkaloids (see Schemes 12.9 and 12.10). Colchicine (54), derived from autumnaline (45) via a remarkable ring-expanding rearrangement, is the most prominent member of this class of tyrosine-derived alkaloids. 

Fig. 2. Battersby, A. R.. et al. Reproduced from Alkaloid biosynthesis. Part XVIII. Biosynthesis of colchicine from the 1-Phenethylisoquinoline system. J. C. S. Perkin Trans. I, 1741 (1972), by kind permission of the Editor...

Alkaloid anti-inflammatory agent autumnaline colchicine Colchicum double haploid elicitors in vitro culture phenethylisoquinoline polyploid... 

Of singular value in unravelling the biosynthesis of colchicine (77) was the idea that this alkaloid could be derived from the androcymbine skeleton and was therefore a modified phenethylisoquinoline. A reasonable way of transforming the androcymbine skeleton into that of colchicine would be to begin by forming the hydroxy-derivative (82). Homoallylic ring expansion and subsequent minor modification would yield colchicine (77) (Fig. 13). 

Battersby AR, Herbert RB, McDonald E, Ramage R, Qements JH (1972b) Alkaloid biosynthesis, part XVni. Biosynthesis of colchicine from the 1-phenethylisoquinoline system. J Chem Soc Perkin Trans 1 1741-1746... 

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