Synthesis of novel 8- and 10-substituted clavine derivatives

Abstract

The hydrogen at C-10 of agroclavine was readily removed by butyl-lithium to give an ambident carbanion. The addition of a range of electrophiles produced 10-substituted agroclavines (2a–l), 8-substituted lysergines (3e–i), and isolysergic acid derivatives (3c, d). Catalytic reduction of 1-methyl-10-propylagroclavine (2c) yielded 1-methyl-10-propylpyroclavine (5b) as the major product. Oxidation of 8-methylthiolysergine (3g) followed by an elimination reaction produced the alkaloid lysergene (7).