Bisbenzylisoquinoline alkaloids analysis

Beside the use of chromatography in isolation of new alkaloids, several analytical chromatographic determinations of bisbenzylisoquinoline alkaloids have been reported. A TLC method for resolution of components of commercial curare is described an unidentified impurity ( 1%), prisms, mp 275°C (dec.) (MeOH), which interferes with crystallization of d-tubocurarine can be removed in this manner (597). Four TLC systems for evaluation of tubocurarine chloride preparations have been developed (598). TLC-UV methods for analysis of tetrandrine in extracts of Stephania tetrandra are described (599,600). 

H. Guinaudeau, A. J. Freyer, and M. Shamma, Nat. Prod. Rep. 3, 477 (1986). Spectroscopy of bisbenzylisoquinoline alkaloids. Tabulation and analysis of high resolution NMR spectra of over 100 bisbenzylisoquinoline alkaloids, arranged by structural types 27 references. 

AN ANALYSIS OF THE DISTRIBUTION OF THE BISBENZYLISOQUINOLINE ALKALOIDS BY STRUCTURAL TYPE 168... 

Volume 14 of this series presents three interesting reviews of research on alkaloids. Chapter I, by Paul L. Schiff, Jr. is a monumental effort, presenting a selective, comprehensive tabular review of research on the bisbenzylisoquinoline alkaloids, with an analysis of the respective alkaloid types. The chapter should serve as a very useful tool for the bench research scientist who is involved in the isolation and elucidation of structures of bisbenzylisoquinoline alkaloids. Moreover, the data in these tables provides the botanical distribution and occurrence (family, genus, species) of the various classes of these alkaloids. The alkaloids are also categorized by their molecular weights and structural types. 

Recently Kondo, Tomita, and Uyeo (55) applied the technique of chromatographic adsorption on alumina to the separation of the alkaloids of Cissampelos insularis Makino and Stephania cepharantha. By this means they isolated, in addition to those known, a new, crystalline, ether-soluble alkaloid whose analysis agreed with that of a bisbenzylisoquinoline alkaloid. This same alkaloid was also found in Chondodendron tomentosum (104) and Stephania capitata Spreng (121). Through a comparison of its properties and that of its derivatives with samples of isochondodendrine dimethyl ether and derivatives provided by Faltis, the Japanese workers (55) established the structure of the new alkaloid as being fully methylated isochondodendrine (LXI). They suggested the names methylisochondodendrine or cycleanine. An attempt to synthesize this alkaloid was not successful (130). Hovrever, by means of sodium and liquid ammonia the compound has been bisected into only one phenolic base whose structure proved to be M-(4 -hydroxybenzyl)-6,7-dimethoxy-iV-methyl-l,2,3,4-tetrahydroisoquinoline (134). This showed that cycleanine (methylisochondodendrine) has the structure (LXI) with both the asymmetric centers levorotatory. 

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. 

As described previously, the origins of the three types of curare are the extracts of Chondodendron (Menispermaceae) and/or Strychnos (Loganiaceae) plants. Among them, the toxic components of Strychnos plants are C-curarine and C-toxiferine I, etc.These constituents are alkaloids derived from tryptophan and are described in the next (Section 2.15).The C- is the initial of calabash. On the other hand, the toxic principle of tubocu-rare is d-tubocurarine, an alkaloid derived from phenylalanine. The alkaloid was first isolated as a hydrochloride from tubocurare and is preserved in the Museum of the British Society of Pharmacy [1]. The chemical structure of d-tubocurarine was first proposed as a bisbenzylisoquinoline with two quaternary ammonium moieties. This was revised in 1970 to be the structure with one tertiary and one quaternary amine after X-ray crystallographic analysis [2]. 

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