Bisbenzylisoquinoline alkaloids, biogenesis

All aporphine-benzylisoquinoline dimers so far isolated from Thalictrum species have identical configurations, suggesting common biogenesis (545). Rules for predicting the configurations of Thalictrum bisbenzylisoquinoline alkaloids have been derived the sole exception is isothalidezine (170), which may be formed by epimerization via an iminium salt of the major co-occurring alkaloid thalidezine (53) (538). 

Barton and Cohen 10) and Erdtman and Wachtmeister 11) have related the concept of free radical coupling of phenols to the biogenesis of natural products, and suggested that bisbenzylisoquinoline alkaloids are formed by this reaction from benzylisoquinoline units. The mechanism of the reaction consists of generation of the resonance-stabilized phenoxy free radical by one-electron oxidation of the phenoxy anion, followed by coupling and tautomerization to form hydroxylated diphenyls or diphenyl ethers. Intermolecular coupling may involve any... 

In order to elucidate the structure of micranthine Bick and Todd (113) subjected 0,0,Ar-trimethylmicranthine methine to ozonolysis and obtained two products. One proved to be 4, 5-diformyl-2-methoxydiphenyl ether (XXXIV). The other was an amino aldehyde which on further degradation (Hofmann) yielded a crystalline substance which from its analysis and properties appeared to be a diformyldimethoxydivinyldi-phenylene dioxide. Bick and Todd deduced the structure of micranthine by recourse to the Faltis theory of the biogenesis of bisbenzylisoquinoline alkaloids. 

Osomine is related to calafatine (Section II,C,9), chillanamine (Section II,C,12), and the seco bases curacautine (Section II,C,16) and talcamine (Section II,C, 105). The biogenesis of these alkaloids probably involves introduction of the C-10 oxygen into a precursor bisbenzylisoquinoline. As with all bisben-zylisoquinolines from the Berberidaceae, the two asymmetric centers are of opposite configuration (57). 

Bisbenzylisoquinolines received importance based on their presence in the pharmacologicaUy active arrow poisons of South American Indians. A recent review gives the chemistry, biogenesis and syntheses [92]. A comprehensive tabular review of over 400 of these phenylalanine-derived alkaloids was published by Guha [93] and Schiff [93]. 

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