Calabash curare alkaloids

For characterization purposes, the Rf values of the alkaloids are given as Rc values, which are displacements calculated with respect to C-curarine, the most abundant and one of the most stable of the calabash curare alkaloids. Thus ... 

Quite early in the chemical studies of Wieland and King, evidence accumulated that the calabash curare alkaloids are indole derivatives, and with present knowledge it is possible to correlate the UV-spectra of many of them with one or another of the following related chromo-phores formally derived from the indole nucleus by oxidation, reduction, and substitution, or combinations of these processes. They are the indoline (II), 2-hydroxyindoline and the derived ethers (III), iV-hydroxy-alkylindoline and its ethers (IV), 2-methyleneindoline or 1-vinylindoline (Va or Vb, respectively), indole (VI), oxindole or 1-acylindoline (Vila or Vllb, respectively), -indoxyl (VIII), and /J-carbolinium (IX) systems it is not possible to distinguish with certainty by spectroscopic methods between the chromophores III and IV, between Va and Vb, or between Vila and Vllb. 

Indeed, all the calabash curare alkaloids with high curarizing activity are now known to possess C40 molecules. The converse, however, is not true, for caracurine V dimethochloride (Section III, C) has the molecular formula yet has a surprisingly low physio-... 

Tubocurarine (I) and the various synthetic curarizing agents such as succinylcholine (LXII) have two quaternary nitrogen atoms set some distance apart. The foregoing experiments allow the calabash curare alkaloids to be placed in the same class of compounds. 

C-Curarine, C40H44N4O++, yields a picrate of mp 306°-307°, and, like C-calebassine, is one of the more frequent and abundant constituents of calabash curare. It was the first crystalline calabash curare alkaloid to be isolated (10). As mentioned earlier, C-curarine is formed from C-dihydrotoxiferine I by photooxidation and is converted into C-fluoro-curarine by the action of concentrated hydrochloric or hydrobromic acid. 

The chemistry of C-curarine has been studied probably more extensively than any other calabash curare alkaloid, and a large number of transformation products, many of unknown structure, have been obtained, e.g., the ultracurines A and B (135). Several further substances have been obtained (132) from some of the reduction products described earlier in the chapter. To avoid confusion, these have not been described in the foregoing account, which includes all the reactions and spectroscopic studies required to establish the structure of C-curarine. 

Streptomyces distallicus the structure elucidation and synthesis have also been made by them.165 A wide variety of porphyrins which are derivatives of porphin (125 R = H) occur in nature and exert three biological functions (a) oxygen storage and transport, as in hemoglobin, (b) cellular respiration as in the cytochromes, and (c) photosynthesis, as in the chlorophylls for detailed discussion of structures and synthesis of naturally occurring porphyrins, see references.166 Recent developments in the chemistry of polypyrrolic compounds have been reviewed.167 Several naturally occurring indole alkaloids have dimeric structures of type B,168 an example of which is c-toxiferine-I, a calabash curare alkaloid found in South American species of Strychnos.169... 

The presentation here has been primarily concerned with the synthetic relationships between the dimeric calabash-curare alkaloids. Literature is only cited when it is not contained in the recently published review articles. In these works all the arguments leading to the structural classification of the alkaloids are fully discussed and the important contributions of the schools of H. Wieland and P. Karrer indicated. 

Acid-catalysed Isomerisations of Calabash-curare Alkaloids.— As has been described, C-toxiferine (38), C-dihydrotoxiferine (46), and C-alkaloid H (49), under the influence of aqueous acid, are readily cleaved via a retro-aldehyde-ammonia addition, into their two halves . This ready cleavage was a key reaction for the elucidation of the structures of these alkaloids. In contrast, the more highly oxidised forms [caracurine II dimetho-salt (50) and C-alkaloid D... 

In continued studies73 of the dimerization of tetrahydrocarbazole derivatives to give the central chromophoric section of the calabash curare alkaloids, it has been shown that the presence of an ethylamino-side-chain can be tolerated thus (83a) gives (84a) and (83b) gives (84b) (Scheme 30). 

Melinonine A. 16,17- Didehydro-16-( methoxycar-bonyl)-4,16a -dimethyloxayohimbanium. [C,jHj7N203] + Calabash-curare alkaloid from Strychnos meltnoniana Bail-lon, Loganiaceae. Isoln and structure Sc blit tier, Hohl. 

The mechanism of the paralysis by the calabash curare alkaloids appears to be truly curariform. Van Maanen (81) showed that they act in the same manner as d-tubocurarine in antagonizing acetylcholine, and Paton and Perry (82) showed that muscles paralyzed by toxiferines respond to direct stimulations and give typical endplate potentials, all of which indicates true myoneural block. 

During the nineteen-fifties and early sixties, there was intense interest and activity in the study of calabash curare alkaloids. These researches led to structural solutions for all the major alkaloids and an impressive body of knowledge was gained concerning the chemistry of these fascinating and complex alkaloids. All this work was covered in Volume VIII. With the major problems solved, there has inevitably been less activity in the field the following sections outline new work published over the past three or four years. 

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