Benzyltetrahydroisoquinoline alkaloids biosynthesis

Bisbenzylisoquinoline alkaloids are dimeric benzyltetrahydroisoquinoline alkaloids that are known for their pharmacological activities. A well-described example is the muscle relaxant (+)-tubocurarine, which in crude form serves as an arrow poison for South American Indian tribes. In the biosynthesis of this broad class of dimeric alkaloids, it has been postulated that the mechanism of phenol coupling proceeds by generation of phenolate radicals followed by radical pairing to form either an inter- or intramolecular C - O or C - C bond. Enzyme studies on the formation of bisbenzylisoquinoline alkaloids indicated that a cytochrome P-450-dependent oxidase catalyzes C - O bound formation in the biosynthesis of berbamunine in Berberis cell suspension culture.15 This enzyme, berbamunine synthase (CYP80A1), is one of the few cytochromes P-450 that can be purified to... 

Oxidative phenol coupling (4, 499-500). Schwartz and Mami have effected oxidative para-ortho coupling of the benzyltetrahydroisoquinoline alkaloid (1) to (2) with TTFA in CH2CI2 ("78 to 20°, overnight) in 23% yield. This oxidative coupling is involved in the biosynthesis of morphine alkaloids, but it has... 

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. 

The biosynthesis of benzyltetrahydroisoquinoline alkaloids has been thoroughly studied—mainly because of the medicinal and commercial importance of opium alkaloids— and commences with the preparation of (5)-reticuline (19). Reticuline then presents a point of divergence and as starting point for the biosynthesis of the previously named tyrosine-derived alkaloids with different skeletal structures [14-16]. The route to (5)-reticuline is outlined in Scheme 12.3. Both reaction partners for the condensation reaction and formation of (S)-norcoclaurine (16) are derived from tyrosine. The aromatic portions in (S)-reticuline (19) possess an ortho-dihydroxylation pattern as present in dopamine (4). However, only the northern portion in 19 is derived from dopamine, and the second hydroxyl functionality in the southern part is introduced after the formation of the tetrahydroisoquinoline ring system. The synthesis of the southern portion in... 

The biosynthesis of the aporphine alkaloids in P. sommferum has been studied (258, 259, 456, 465). In 1911, Gadamer postulated that the biosynthesis of the aporphine alkaloid glaucine (24h) proceeds via the simple benzyltetrahydroisoquinolines (466). Later, this hypothesis was experimentally confirmed, but some of the problems remained unresolved owing to the inadequate technique employed then. Recently, some authors have returned to this problem (152,258,259,467). By addition of N—CH3 labeled reticuline to a nutrient solution it was shown that, from the thus... 

Barton DHR, Potter CJ, Widdowson DA (1974) Phenol Oxidation and Biosynthesis. Part XXIII. On the Benzyltetrahydroisoquinoline Origins of the Erythrina Alkaloids. I Chem Soc Perkin Trans 1 346... 

Barton, D.H.R. Potter, C.J. Widdowson, D.A. Phenol oxidation and biosynthesis Part XXIII. On the benzyltetrahydroisoquinoline origins of the Erytrina alkaloids. J. Chem. 

The 1-benzyltetrahydroisoquinoline skeleton is a very important one in the field of plant alkaloids and is the subject of various, interesting modifications. Indeed, with the exception of terpenoid indole alkaloids, no other skeleton is so diversely modified. In this family of benzylisoquinolines, reticuline (25) is preeminent, being a key intermediate in the biosynthesis of many alkaloids. 

Martin RO, Warren ME Jr, Rapoport H (1967) The biosynthesis of opium alkaloids. Reticuline as the benzyltetrahydroisoquinoline precursor of thebaine in biosynthesis with carbon-14 dioxide. Biochemistry 6 2355-2363... 

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