Ergot alkaloids studies

Floss HG, Tscheng-Lin M, Chang C, Naidoo B, Balir GE, Abou-Chaar Cl, Cassady JM (1974) Biosynthesis of ergot alkaloids. Studies on the mechanism of the conversion of chanoclavine-I into tetracyclic ergolines. J Am Chem Soc 96 1898-1909... 

In his general studies aimed at the synthesis of ergot alkaloids, Hegedus effected the coupling of dihaloindole 79 with the zinc reagent 80, generated in situ from l-methoxy-l,2-propadiene, to afford ketene 81 [21],... 

Yang described the Pd-induced cyclization of an aryl bromide onto a pendant cyano group leading to y-carbolines and related compounds [488], Genet studied the use of chiral palladium complexes in the construction of the C-ring of ergot alkaloids, a study that culminated in a synthesis of (-)-chanoclavine I [489-491]. For example, nitroindole 388 is cyclized to 389 in 57% yield and with enantioselectivities of up to 95% using Pd(OAc)2 and (S)-(-)-BINAP. 

There is some interesting new methodology that has been worked out in the course of these studies 73>76>. in general, stereospecificity relations of this sort are examined with the help of other enzyme reactions of known stereospecificity. When mevalonic acid (lactone form, 8 is fed to Claviceps, the 5-Hs atom is incorporated into the ergot alkaloids agroclavin 9a and elymoclavin 9b, whereas the 5Hr, atom is lost. 

Bhattacharji, S., A. J. Birch, A. Brack, A. Hofmann, H. Kobel, D. C. C. Smith, H. Smith and J. Winter Studies in Relation to Biosynthesis. Part XXVII. The Biosynthesis of Ergot Alkaloids. J. cheni. Soc. [London] 1962, 421. 

Ergot Alkaloids. The ergot alkaloid hydergine was introduced in the 1940s and was in fact the first medication approved by the FDA to enhance cognition in dementia patients. It continues to be used occasionally today, but numerous studies have not shown any clear benefit for hydergine or other ergot alkaloids. We therefore do not recommend its routine use. 

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. 

Cyclols Stable molecules obtained by the addition of a heteroatom nucleophile to the carbonyl group of lactams are not very common. The side-chain moiety of the ergot alkaloids (e.g., 50) is one of the earliest examples of such a cyclolic structure (75FOR51) identified. This has given rise to a number of studies on the synthesis and chemical transformations of such units. The discussion below is confined to cyclols related to or arising from piperazine-2,5-diones. 

The photoaddition of water to the ergot alkaloids has been the subject of a number of studies,214,215 and the structures of the adducts have been elucidated. 

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. 

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