Bis-benzyltetrahydroisoquinoline

The intermolecular coupling of phenols is used extensively in what are believed to be biomimetic alkaloid syntheses. Aqueous solutions of iron(lll) salts are most frequently used as the oxidising agent and the dimerization process must involve phenoxy radicals. Examples are the dimerization of orcinol 21 [114] and the formation of bis-benzyltetrahydroisoquinolines 22 [115],... 

The alkaloid content of curare is from 4% to 7%. The most important constituent in menispermaceous curare is the bis-benzyltetrahydroisoquinoline alkaloid (+)-tubocurarine (Figure 6.48). This is a monoquaternary ammonium salt, and is water soluble. Other main alkaloids include non-quaternary dimeric structures, e.g. isochondrodendrine and curine (bebeerine) (Figure 6.48), which appear to be derived from two molecules of (R)-N-methylcoclaurine, with the former also displaying a different coupling mode. The constituents in loganiaceous curare (from calabash curare, i.e. Strychnos toxifera) are even more complex, and a series of 12 quaternary dimeric strychnine-like alkaloids has been identified, e.g. C-toxiferine (toxiferine-1) (see page 359). 

The above-ground parts of C. olivascens Bameby et Krukoff have yielded the bis-benzyltetrahydroisoquinolines (—)-2-norlimacine (20a), a new base (—)-caryolivine (20c), and l,2-dehydro-2-norlimacusine (21a) as the principal components of the alkaloid mixture (412). On the other hand, the fruits have furnished eight non-quaternary bases, including (H-)-coclaurine (26a), (—)-stepharine (27b), the protoberberine (+)-pseudopalmatine (34f), and a series of 2,3,10,11-tetra-substituted tetrahydroprotoberberines (34a-e). Bis-benzyltetrahydroisoquinoline alkaloids appear to be absent from the fruit (413). 

Only bis-tertiary and -quaternary dimeric indole alkaloids have so far been isolated from Strychnos materials, but the former should, just like the bis-benzyltetrahydroisoquinoline bases already discussed, quatemize on treatment with methyl iodide. The fact that there was no increased toxicity in the experiments by Marini-Bettolo et al. suggests that dimeric tertiary alkaloids were also absent from their Strychnos material, so that there was no opportunity for AT-methylation and hence for an increase in curarizing activity. But here again, the point needs more detailed study. 

The neuromuscular blocking potencies of various d- and l-NN-dialkyltetrahydropapaverinium iodides and of NN -decamethylene-bis-tetrahydropapaverinium compounds like (56) have been examined. Several compounds like (57) and (58) have been prepared and their sympathomimetic activities compared with that of the phenolic benzyltetrahydroisoquinoline to which they bear the closest resemblance. The synthesis and pharmacological properties of... 

In accord with the greater range of menispermaceous genera that are utilized as components of curares, chemical studies have shown that they contain a wide variety of isoquinoline and related alkaloids bis-benzyltetrahydroiso-quinolines, benzyltetrahydroisoquinolines, proaporphines, aporphines, oxo-aporphines, azailuoranthenes, tropoloisoquinolines, and isoquinolobenzaze-... 

The alkaloids occurring in Chondrodendron species have long been recognized as benzyltetrahydroisoquinoline derivatives. A variety of bis- and monoquaternary and bis-tertiary bases has been found, in which the two halves are joined head-to-tail through two ether linkages in the curine skeleton between 8-12 and 11-7 (cf. 18a) and in the isochondrodendrine skeleton between 8-12 and 12-8 (19a). It is the quaternary alkaloids that are the main active principles. 

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