Lysergic acid a-hydroxyethylamide

A plausible precursor for lysergic acid a-hydroxyethylamide (116) is lysergyl-alanine (117). Administration of D-lysergyl-L-alanine with a " C label as shown in (117) to Claviceps paspali, however, gave an enhanced yield of ergometrine (118) and very little radio-activity in the side chain of (116) degradation of the ergometrine showed that the label was confined to C-2 plus C-3 of the alaninol... 

Fig. 4.7 Biosynthesis of ergohne alkaloids IV. Presumable formation of simple lysergic acid amides occurring in Claviceps spp. and certain convolvulaceous species lysergoyl adenylate is transformed to an enzyme-linked lysergoyl-L-alanine by a peptide synthetase different to LPS the low-molecular direct precursor of ergometrine released from the enzyme might be the corresponding aldehyde which in turn could be reduced in the last step the homologous lysergic acid a-hydroxyethylamide might be produced in a similar manner...

Flieger, M., Sedmera, R, Vokoun, J., feicSicova, A. and feehacek, Z. (1982) Separation of four isomers of lysergic acid a-hydroxyethylamide by liquid chromatography and their spectroscopic identification./. Chromatogr., 236, 453-459. 

This group of ergot alkaloids encompasses both compounds directly applicable in therapy (ergometrine) and compounds, which can be employed for the production of semisynthetic alkaloids (lysergic acid, ergine, lysergic acid a-hydroxyethylamide and their isomers, paspalic acid). 

Lysergic acid and paspalic acid were isolated in 1964 from cultures of C. paspali (Kobel et al, 1964) and in 1966 from cultures of C. purpurea (Castagnoli and Mantle, 1966). Ergine (Arcamone et al, 1961 Kobel et al, 1964) and lysergic acid a-hydroxyethylamide (Arcamone etal, 1960 Flieger etal, 1982) were also isolated from the cultures of C. paspali. Ergometrine (ergonovine) was isolated from both C. purpurea (Stoll, 1952) and C. paspali (Kobel et al, 1964). 

C,9- H]Chanoclavine I was converted to elymoclavine with 70% tritium retention. (4R)-[2- " C,4- H]Mevalonate also gave elymoclavine and lysergic acid a-hydroxyethylamide with 70% tritium retention (Floss et ai, 1968). The percent tritium retention varied in the range 40-80% with the rate of alkaloid biosynthesis (Floss et al., 1974a). Low rates of alkaloid production correlated with low tritium retention at C(9). A mechanism was proposed to account for the loss of tritium (Fig. 6). The mechanism involves... 

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