Dihydrolysergic acid

The formation of l-methyl-5-aminonaphthalene when dihydro-lysergic acid is fused with potassium hydroxide requires rings (A) and (Cb The presence of an indole nueleus (rings (A) and (B) ) is established by the formation of 3 4-dimethylindole, m.p. 115-7°, pierate, m.p. 185-7°, by decarboxylation of an indole acid obtained when dihydrolysergic acid is fused with potassium hydroxide. ... 

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 —... 

Lysergic Acid from 2,3-Dihydrolysergic Acid JACS 78,3114 (1956)... 

The stereochemistry of the 10-methoxy-dihydrolysergic acids [352]— [355] has been confirmed by 13C NMR spectroscopy. (219) Com-... 

Indeed, one pair of enantiomers of the formula 26 could be converted to the already known 2,3-dihydrolysergic acid methyl ester 27 in 15% yield by the action of sodium amide in liquid ammonia. Oxidation with activated Mn02 finally led to ( )-lysergic acid methyl ester 28. 

Some of the substitution reactions, mainly at the indole-nitrogen as well as halogenation at C-2 have already been discussed in Volume VIII. Oxidation of 2,3-dihydrolysergic acid derivatives with Fremy s salt leads to derivatives of 12-hydroxylysergic acid (41) which have recently been shown to be significant in metabolic studies (41a). 

Nitration of derivatives of 9,10-dihydrolysergic acid with fuming nitric acid in acetic anhydride in the presence of urea has been reported (44a) to lead to the 2-nitro derivatives though only in 5-20% yield. 

The reduction product of dihydrolysergic acid amide, 6-methyl-8/S-aminomethyl-10a-ergoline proved to be a very fruitful starting material for the development of new active derivatives (108). 

The scope of the reaction was further explored by attempting the amidation of 9,10-dihydrolysergic acid. 

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

The isomerization proceeds via an intermediate compound that is symmetrical at the C-8 position and that exhibits a continuous conjugated system of double bonds stretching from the enol double bond up to the indole system. Thus, isomerization of dihydrolysergic acids, in... 

Fig. 1. TTV-spectrum in methanol. I Lysergic acid II dihydrolysergic acid.

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). 

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