The Total Synthesis of Lysergic Acid

Abstract

The Total Synthesis of Lysergic Acid 3087 in the ultracentrifuge,8'41 as are polysaccharides generally.With respect to immunological homogeneity it has been established by several investigators that proteins which are non-homogeneous in the ultracentrifuge,42 electrophoretically4 3 and in amino acid composition31 may be immunochemically uniform.The relationship of amino acid composition to specificity among the blood group substances is not clear from the data presented. Work on the inhibition by oligosaccharides of the precipitation of blood group substances with specific antibody suggests that the carbohydrate presents binding sites for the immunological reaction.44 In view of the general similarity of amino acid composition, it is (41) R. A.

Substituted Tetralins II: Preparation of 2-Amino-4-carbamyl-6-methoxy-4-methyltetralin

“…Aluminum chloride was not investigated because of its propensity to cause cleavage ofethers. The initial reagent employed was polyphosphoric acid, which has found extensive use in similar cyclizations (7)(8)(9). Although nearly a quantitative yield of crude ketonic material was obtained, the removal of a low-melting contaminant afforded only about a 75% yield of a pure tetralone, which was subsequently shown to be the amidotetralone (VIII) rather than the cyanotetralone (VII).…”

“…The hindered nature of the nitrile group of VII became apparent when it was subjected to vigorous acidcatalyzed hydrolysis conditions without alteration. The nitrile (VII) was converted to the amide (VIII) in yields of 85-90% using alkaline hydrogen peroxide in a Radziszewski reaction (7,15).…”

Synthetic Route to Ergot Alkaloids

“…To our pleasant surprise, we found that, contrary to [9], bromo ketone 4d [19] can be subjected to a substitution reaction with amine 26 providing us with the so far unknown but much sought-after, even mistakenly claimed [8], product 27a (yield 35%) if one has the patience to allow the reaction to proceed at room temperature in toluene (Scheme 5). The amine component 26 was already known and could easily be prepared [3]. After a simple deacylation (3 27b; 80%) with methylamine and subsequent deprotection of the ketone function, the desired compound 28 (80%) was for the first time in our hands.…”

“…The first synthesis of racemic lysergic acid was effected by Woodward and Kornfeld [3] in 1956. One of their main problems was to prepare ring C from the otherwise easily accessible 1H-indole-3-propanoic acid (3) since the ring closure of the corresponding acid chloride occurred at the more reactive pyrrole ring instead of the benzene ring.…”

“…The ring closure of 28 leading to the unsaturated ketone (AE)-29 2 ) by intramolecular aldol condensation seems to be an easy task, but with a great number of well-established agents (from t BuOK through super bases to (Me 3 Si) 2 NLi), not even a trace of the desired tetracyclic compound could be detected. It is worth noting, and not easy to explain, that in the dihydro-1H-indole series, this ring closure had been carried out [3]; however, a similar intramolecular ring closure of compounds with a sulfone group instead of the indole N-atom also failed. We succeeded in performing the reaction with a LiBr/Et 3 N system [24] [25], which was first used for condensation by Eschenmoser and co-workers in the case of different S-containing compounds.…”