Tyrosine phenethylisoquinoline

Lilaceae also contain 1-phenethylisoquinoline alkaloids, it was suggested [82) that the homoerythrina derivatives are biosynthesized along a pathway analogous to that followed by the Erythrina alkaloids themselves (Scheme 35). Some preliminary results from feeding experiments (121) support this view ( )-[2-14C]tyrosine causes specific labeling of C-8 in 77a. 

Cephalotaxus Alkaloids.—Preliminary results indicate that the homo-Erythrina alkaloid schelhammeridine (52) derives from phenylalanine and tyrosine by way of a phenethylisoquinoline precursor [as (53)].52 Previous evidence for the biosynthesis of the related alkaloid cephalotaxine (54), obtained with tyrosine labelled in the side-chain, has indicated a different pathway which involves two molecules of this amino-acid.53 Recently, however, tyrosine labelled in the aromatic ring was examined as a cephalotaxine precursor and was found54 to label ring A of (54) almost exclusively, i.e. only one unit of tyrosine is used for biosynthesis. This is obviously inconsistent with the previous evidence and the early incorporations are... 

Tyrosine was indeed found to be a precursor for cephalotaxine (122) but the labelling pattern precluded a phenethylisoquinoline intermediate. Thus [3- C]tyrosine gave cephalotaxine with 68% of the activity at C-16 and 32% at C-9 (Scheme 14), whereas [2- C]tyrosine labelled C-17 to the extent of 37% with no label at C-2 or C-3. It is to be noted that both samples of tyrosine were incorporated to similar extents and yet the expected correlation of activity between C-16 and C-17 is poor. This was attributed to some scatter of the label from C-2 of tyrosine. [l- CjTyrosine was only incorporated at a very low level and the activity appeared to be scattered. The results clearly implicate two molecules of tyrosine with loss of the carboxy-functions in a novel pathway to cephalotaxine. A scheme which is consistent with these results has been tentatively advanced (Scheme 15). This hypothesis is capable of further testing, which is in progress. 

Biosynthesis The concomitant occurrence of C. a. and homoerythrina alkaloids indicates a common biosynthesis. Both types of alkaloids are derived from 1-phenethylisoquinoline with (see phenethyltetrahydroi-soquinoline alkaloids) ring A originating from tyrosine and ring B from phenylalanine. The acid components, e. g., harringtonic, isoharringtonic, and deoxyharring-tonic acids are derived from leucine. 

The steps which lie between phenylalanine and tyrosine on the one hand and the first identified phenethylisoquinoline (81) are not completely understood but dopamine (4) is an intermediate derived from tyrosine, and cinnamic acid is an intermedi-... 

The manifold possibilities for the elaboration of structurally intriguing natural products via the aforementioned oxidative aryl-aryl coupling reactions emphasize the importance of phenolic coupling reactions in the biosynthesis of tyrosine-derived alkaloids. This important reaction not only plays a significant role in the biosynthesis of benzyltetrahydroisoquinoline alkaloids but also for the construction of phenethylisoquinoline alkaloids and Amaryllidaceae constituents, discussed in the following sections. 

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. 

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