IsoLysergic acid

The dihydro-bases of type (I) yield on treatment with hydrazine the expected (—)-dihydro-d-wolysergic acid (I) hydrazide, but on hydrolysis with alkali the reduced isolysergic acid residue is irreversibly isomerised to the dihydrolysergic acid residue and the product obtained is (—)-dihydro-d-lysergic acid (c/. p. 532). 

The second type, dihydro-bases (II), hydrolyses with alkali or with hydrazine to (+)-dihydro-d-wolysergic acid (II), which is probably identical with the y-dihydrolysergic acid of Jacobs and Craig. The principal characters of the dihydro-lysergic and isolysergic acids and their derivatives are summarised in the following table —... 

To a freshly prepared solution of 2 parts of d-isolysergic acid azide in 300 parts of ether is added an ethereal solution of 2 parts of d-2-aminobutanol-1 and the mixture is left to stand at room temperature during 12 hours. The yellowish clear solution is then washed several times with some water, dried over sodium sulfate and the ether evaporated in vacuo. The crystallized residue is treated with a small quantity of acetone and filtered. Yield ... 

The alcoholic ethereal filtrate is then dried over calcined potassium carbonate and the solution evaporated, whereby 0.9 to 1 part of a mixture of d-lysergic acid-d-l-hydroxybutyl-amide-2 and of d-isolysergic acid-d-l-hvdroxvbutylamide-2 is obtained. In order to separate the isomers, the residue is dissolved in 15 parts of hot chloroform and filtered from the small quantity of inorganic salt, whereby on cooling down, the difficultly soluble chloroform compound of d-lysergic acid-d-l hvdroxvbutylamide-2 crystallizes out. Yield 0.4 part. This compound can be recrystallized from hot benzene, whereby crystals melting... 

According to the same procedure, the compound 14 2-bromo-D-isolysergic acid ethynylcyclohexylamide was obtained. The compound crystallizes from dichloro-methane C24H26BrN30 x 0.6 CH2CI2 m.p. = 154 - 157°C [a]o = +431.8°... 

Bromocriptine mesilate exhibits fluorescence like the other lysergic and isolysergic acid type alcaloids. In 2 percent ethanolic tartaric acid solution, the emission maximum appears at 402 nm (excitation at 325 nm). See fig. 3. 

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. 

Under ordinary conditions, about 20% of (I) will be converted by the action of hot water, etc., to the inactive isolysergic acid. Most of this remains in solution and can be isomerized to (1) as described above, or it can be converted to iso-LSD by any of the methods described later and isomerized to LSD (see method 1). 

Ergot Claviceps purpurea Fungus of-isolysergic acid of-lysergic acid... 

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... 

K. Bailey, D. Verner, and D. Legault, Distinction of some dialkyl amides of lysergic and isolysergic acids from LSD, J. Assoc. Off. Chem., 56 88 (1973). 

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