Bisbenzylisoquinoline

In addition to the foregoing benzylwoquinoline alkaloids all derived from Papauer spp, two other members of the group, coclaurine and iso-coclaurine are described in the bisbenzylisoquinoline group (p. 349) with which they are naturally associated. 

Coclaurine is of special interest since worcoclaurine (I MeO HO) can be regarded as the parent substance from which by ether formation the series of bisbenzylisoquinoline alkaloids can arise. Thus, the dauricine type of alkaloid may be formed by a single ether linkage between the 4 -hydroxyl of one woreoclaurine molecule and a hydrogen atom ortho to the 4 -hydroxyl of a second molecule. 

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... 

Fig. 10.3 Reaction catalyzed by the cytochrome P-450-dependent oxidase berbamunine synthase (CYP80A1). This enzyme creates a branchpoint in the (5)-reticuline biosynthetic pathway to form the bisbenzylisoquinoline alkaloids.

Otshudi, A. L., Apers, S., Pieters, L., Claeys, M., Pannecouque, C., Clerq, E. de, Van Zeebroeck, A., Lauwers, S., Frdddrich, M. and Foriers, A. 2005. Biologically active bisbenzylisoquinoline alkaloids from the root bark of Epinetrum villosum. Journal of Ethnopharmacology, 102 89-94. 

Leclerq, J., Quetin, J., De Pauw-Gillet, M.-CL, Bassleer, R. and Angenot, L. 1987. Antimitotic and cytotoxic activities of guattegaumerine, a bisbenzylisoquinoline alkaloid. Planta Medica, 116-117. 

Kuroda, H., Nakazawa, S., Katagiri, K., Shiratori, O., Kozuka, M., Fujitani, K. and Tomita, M. 1976. Antitumor effects of bisbenzylisoquinoline alkaloids. Chemistry and Pharmacology Bulletin, 24 2413-2420. 

In the bisbenzylisoquinolines the size of the macrocyclic system affects the chemical shifts of some groupings of protons in a characteristic way. In certain conformations of the 21-membered ring in 5-7 ether linked systems the 2- and 6-substituents lie over aryl rings with a consequent shift to lower frequency. This is illustrated by the H NMR spectrum of thalictine [39] (38) which shows absorption for the 8-and 8 -protons to low frequency of the other aromatic protons. 

Although it is almost a cliche to point out the ever-accelerating pace of scientific development, since the last review on the bisbenzylisoquinoline alkaloids in... 

The format follows that of the earlier review. The subject of synthesis, however, which formerly constituted a separate chapter, is included in this work, and other coverage has been expanded, particularly in the areas of plant biochemistry and pharmacology. The tabulation of all known bisbenzylisoquinoline alkaloids has been revised and updated. A section listing other major review articles on these alkaloids is also included, and the reader may wish to consult some of these for extensive physical data. In keeping with the original purpose of this treatise, we have tried for a comprehensive overview, with strong emphasis on the specific chemistry of the bisbenzylisoquinoline alkaloids, rather than an exhaustively detailed presentation. 

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