Experiments towards the synthesis of the ergot alkaloids and related structures. Part 4. Lysergic acid–an attempted ‘endo-amide’ approach

Abstract

Two attempts to synthesise the tricyclic α-keto-amide (6) are described. In the first, 1,2,3,4-tetradihydro-2-methylaminonaphthalen-1-one hydrochloride (3) was allowed to react with pyridine–hydroxymaleic anhydride at –20 °C and then at room temperature to give a complex mixture from which the naphth[1,2-b]-1,4-oxazinone (14), 2-pyruvamido-1-tetralone (16; R = Ac) contaminated with the oxazinone (14) and the phenolic acid (13c) were isolated. A tetracyclic oxazinone was also obtained from the appropriate methylaminotetrahydroacenaphthenone but not from the corresponding benz[cd]indolone (7; R = NHMe.HCl). In the second, the N-methyldione (10) was converted in three stages into the tricyclic acid (13c) which proved unexpectedly stable. However, its triethylamine salt lost carbon dioxide at 140 °C to give not the required keto-amide (6) but the isomeric hydroxybenz[f]quinolone (13d). Both the oxazinone (14) and the impure pyruvamido-ketone (16; R = Ac) were converted within seconds by treatment with 2M-sodium hydroxide into the sparingly soluble sodium salt of the phenol (13d) as was the pure pyruvamido ketone whose synthesis is described.