Lysergic acid and derivatives

Non-terpenoid Alkaloids.—De-A-methylation of lysergic acid and derivatives can be achieved using a variant14 of the classical von Braun procedure which involves successive treatments with cyanogen bromide and zinc-acetic acid (or hydrogen-Raney nickel). 

Bromocriptine is rapidly and completely metabolised in animals and man. The major components of the urinary metabolites have been identified as 2-bromo-lysergic acid and 2-bro-mo-isolysergic acid. Apart from the hydrolytic cleavage of the amine bond and the isomerization at position 8 of the lysergic acid moiety, a third principal biotransformation pathway consists in the oxidative attack of the molecule at the proline fragment of the peptide part, predominantly at position 8, giving rise to the formation of a number of hydroxylated and further oxidized derivatives of bromocriptine, and in addition of conjugated derivatives thereof. 

The conformation of the D-ring in the dimethylamides of lysergic acid and of isolysergic acid has been studied by H NMR spectroscopy. The lysergic acid derivative exists in the conformation [345] with the halfchair D-ring and the pseudo-equatorial amide function. This conformation is supported by allylic coupling between the 5- and 9-protons of... 

The delicate structures as well as the interesting patterns of pharmacological activity of certain ergot alkaloids have received continuous attention among synthetic chemists. This is especially true of derivatives of lysergic acid, and this chapter will be devoted to the most remarkable developments in syntheses of this class of natural compounds. 

In the meantime amides of the A8,9 isomer (13) of lysergic acid and their derivatives have been prepared (42). Homologization of lysergic acid (43) to the so-called homolysergic acid (44) has been achieved (43) as indicated below. The same reaction was also carried out later on with the 9,10-dihydro derivatives (44). 

The 9,10 double bond of lysergic acid has also been used for some interesting transformations for example, hydrogenation leads stereo-specifically to the lOa-ergoline derivatives. The also well-known photo-lytic addition of water yields predominantly the 10a-hydroxyergoline (48) and, when carried out in acidified methanol, mainly lOa-methoxy-ergolines (49) can be isolated. Hydroboration of lysergic acid and... 

C. Lysergic acid and related alkaloids Lysergic acid derivatives (30) Isolated rat liver Chanoclavine (31) Pigeon liver preparation... 

A. Lysergic Acid and Dihydrolysergic Acid Derivatives of the Acid Amide... 

B. Derivatives of lysergic acid and isolysergic acid of the peptide type... 

Measurement of pK values of lysergic acid and dihydrolysergic acid derivatives and the analysis of their IR-spectra confirm that these structural configurations are indeed correct (19). 

Halogenated lysergic acid and dihydrolysergic acid derivatives may easily be differentiated from the starting materials containing no... 

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... 

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