Derivatives of Ergot Alkaloids

The potent and versatile pharmacological activity of natural ergot alkaloids prompted investigations on the relationship between their chemical structure and physiological action. It also caused the natural alkaloids to be modified chemically and the resulting variations of pharmacological and therapeutic action to be studied. 

Lysergic Acid and Dihydrolysergic Acid Derivatives of the Acid Amide Type 

In the last few years, further processes for the partial synthesis of ergometrine and other lysergic acid derivatives of the amide type have been discovered. 

In accordance with the method of Garbrecht (144), the lithium salt of lysergic acid is converted in dimethylformamide solution with SO3 to form the mixed lysergic acid sulfuric acid anhydride which reacts with primary or secondary amines to give a good yield of the corresponding lysergic acid amides. 

Similarly, the process according to Pioch (145) is effected via a mixed anhydride, namely, via the mixed lysergic acid trifluoroacetic anhydride. In this case, however, the yields of lysergic acid amide are usually not as good as in the SO3 process. 

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Thus, our tungstate method is proved to be applicable even to ergot alkaloids. Synthesis of 316 and various 1-hydroxy derivatives of ergot alkaloids could be carried out in the near future. 

Table 2. Physico-chemical properties of 2-(2, 3 -dihydro-3 -oxo-r,2 -benzisothiazolyl-r,r dioxide) derivatives of ergot alkaloids U... 

Kfen, V. and Sedmera, P. (1996) N-l-Trimethylsilyl derivatives of ergot alkaloids. Collect. Czech. Chem. Commun., 61,1248-1253. 

Stoll, Hofmann and Petrzilka (1946) have also succeeded in obtaining dihydro-derivatives of this series (ergotinine type) of ergot alkaloids. Each of these bases yields two dihydro-derivatives, distinguished as isomerides I and II. Their chief characteristics are siunmarised in the following table —... 

Note It is possible to differentiate amino acids by color on the basis of the markedly different shades produced [2, 3]. Proline and hydroxyproline, that only react weakly with ninhydrin, also yield pink-red colored derivatives [2]. Ergot alkaloids and LSD are detected by spraying with 10% hydrochloric add and then heating to 110°C for 20 min after they have been treated with the reagent [9]. Ergot alkaloids and LSD yield red to purple zones when treated in this manner other alkaloids, e.g. reserpine, emetine, quinine, strychnine, pilocarpine, atropine, scopolamine, cocaine and opium alkaloids, do not give a reaction [9]. 

Hindmarch I, Parrott AC and Lanza M (1979). The effects of ergot alkaloid derivative (Hydergine) on aspects of psychomotor performance, arousal, and cognitive processing ability. Journal of Clinical Pharmacology, 19, 726-732. 

Ergot alkaloids were the first adrenoblockers to be studied. Despite the fact that the majority of ergot alkaloids exhibit a-adrenoblocking activity, their pharmacology is often different. In terms of chemistry, ergotamine and ergonovine are derivatives of lysergic acid. 

IX. The Pharmacology and Therapeutic Use of Ergot Alkaloids and Their Derivatives... 

Much more successful turned out to be the concept of chiral anion exchangers. So far, there are mainly two significant contributions reported (1) the use of cationic. selectors derived from cinchona alkaloids and (2) the use of cationic selectors derived from ergot alkaloids. 

Jolivet A, Robyn C, Huraux-Rendu C, Gautray JP. Effet de derives des alcaloides de I ergot de seigle sur la secretion lactee dans le post-partum immediat. [Effect of ergot alkaloid derivatives on milk secretion in the immediate postpartum period.] J Gynecol Obstet Biol Reprod (Paris) 1978 7(l) 129-34. 

Recently, a large series of glycosides of ergot alkaloids was prepared using both chemical and enzymatic methods [131,132,133,134]. Preliminary results obtained indicate that some of these derivatives could have very interesting activities compared to their aglycons. 

Derivation Alkaline hydrolysis of ergot alkaloids, organic synthesis. 

Cerletti, A. Doepfner, W. Comparative Study on the Serotonin Antagonism of Amide Derivatives of Lysergic Acid and of Ergot Alkaloids J. Pharmacol Exp. Then (1958) 122 124-136... 

Lefebvre, C.L. Ergot of Paspalum Phytopathology (1939) 29 365-367 Lehrfeld, J. Burkman, AM. Gearien, J.E. Synthesis of 6-Substi-tuted Nicotinic Acid Derivatives as Analogs of Ergot Alkaloids Journal of Medicinal Chemistry (1964) 7 150-154... 

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