Ergot alkaloids utilization

Swiss workers have utilized this methodology for the synthesis of several ergot alkaloids (69HCA1549 70HCA1278). 

Ergot Alkaloids.—4-(yy-Dimethylallyl)tryptophan (122) is the first intermediate beyond tryptophan in ergot alkaloid biosynthesis. Chanoclavine-I (127) is the first tricyclic base (cf. Vol. 10, p. 26, and ref. 2). Recently, (124 labels as shown) has been found to be a very efficient and intact precursor for elymoclavine (128).45 The high level of incorporation indicates that (123) is a probable intermediate situated between (122) and (127). The decarboxylation product (125) was not utilized for biosynthesis, so, although decarboxylation of (123) is required for the conversion of (123) into (127), either it is intimately associated with ring-closure or an imine that is related to (126) is involved. 

Protoplasts of C. purpurea have been prepared which are able to synthesize the peptidic ergot alkaloids ergotamine (69) and ergocryptine de novo.63 Various radioactive amino-acids were incorporated into the alkaloids, and D-lysergic acid (70) stimulated their utilization. It was the only precursor to stimulate the synthesis of alkaloids, and the proposal was made that the concentration of (70) in the cells is a rate-limiting factor in alkaloid synthesis. 

All ergot alkaloids which have so far been used therapeutically are lysergic acid derivatives. Representatives of the second main group, the clavine alkaloids, have also been found to be pharmacodynamically active, but as yet, none has been found to exert effects that can be utilized in therapy. The uterotonic and sympatholytic actions are less prominent in their pharmacological spectra of activity but, for example, elymoclavine and agroclavine have a pronounced central excitatory action which is attributed to their stimulation of sympathetic centers (172). 

There are approximately 20 natural ergot alkaloids. A few of these, plus some derivatives, are used pharmacologically. Several act via 5HT receptors, but a- and D2 receptors are also utilized. The clinical uses and properties of specific ergots are indicated. 

The utilization of various nitrogen sources in the production of ergot alkaloids in C. purpurea cultures has received detailed investigation.The relationship between the amount of cell-pool tryptophan, time, and the synthesis of ergot alkaloids in Aspergillus fumigatus has been noted. 

The clinical utility of natural EA like 3 and 4 was a prelude to broader and more precise clinical applications of semisynthetic derivatives of 1 and ergopeptines. Mukherjee and Menge (103) provide a detailed review of ergot-alkaloid modifications and the effects on their pharmacological activities. 

Schmauder, H.-P. (1982) Ergot. Saprophytic production of ergot alkaloids. In Atal, C.K. and Kapur, B.M. (eds.) Cultivation and Utilization of Medicinal Plants. Council of Sci. and Ind. Res., Jammu-Tawi, India. 

Evers, N. (1927) A colour test for ergot alkaloids. Pharm. J. Pharmacist, 25, 721-723. Ezan, E., Ardouin, T., Delhotal Landes, B., Flouvat, B., Hanslik, T., Legeai, J.M. and Grognet, J.-M. (1996) Bioequivalence study of a-dihydroergocryptine utility of metabolite evaluation. Int. J. Clin. Pharmacol. Ther., 34, 32-37. 

Kyhal, J., Svohoda, E. and Kleinerova, E. (1978) Utilization of malic acid and its importance for the biosynthesis of peptide ergot alkaloids. Abstract Book, 14th Ann. Meet, of Czechoslov. Soc. Microbiol., Prague, Czechoslovakia, October 17-19,1978. 

The variety of applications of ion-pair chromatography illustrates the versatility of this technique in separation science. Early applications utilized a normal-phase solid support and explored the resolution of amines and alkyl ammonium ions with an anionic counter ion such as picrate or naphthalene 2-sulfonate (41, 42, 89, 90, 219). These results prompted investigations into the suitability of ion-pair chromatography as a technique for use in pharmaceutical analysis such as the determination of ergot alkaloids (333). 

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