Ergot skeleton

In a related approach, Murakami synthesized clavicipitic acid and costaclavine [79], and later extended this chemistry to a synthesis of chanoclavine-1 featuring the intramolecular Heck vinylation 251 to 252 [265]. The corresponding enone failed to cyclize under these conditions. Noteworthy is that radical cyclizations, which often compete successfully with Heck reactions, were poor in this system. Martin developed a novel route to the ergot skeleton that features a Heck cyclization of bromo alkyne 253 [266]. 

Most of the ergot alkaloids used in therapy are semisynthetic derivatives. There exists a continuous search for new, more potent or more selective EA derivatives. Because of alkaloid complexity and the sensitivity of the EA skeleton to harsh conditions, biotransformation methods are more often used for their derivatization [11]. 

CHEMISTRY OF THE ERGOT-ALKALOIDS The ergot alkaloids have an ergoline skeleton, which forms a part of the common ingredient D-lysergic acid, which has two... 

Procedures for preparing new steroid intermediates and ergot alkaloids have been further developed. A new method of bioconversion was elaborated for the degradation of sterine side-chains, which allowed selective degradation of the side-chain without damaging the sterane skeleton. 

Intramolecular aryne cycloaddition.1 A new approach to the basic skeleton of ergot alkaloids involves an intramolecular cyclization of the amide 1 to form 2, effected with LDA at —30°. 

Ergot Alkaloids.—The elaboration of the tetracyclic ergoline skeleton, as represented by agroclavine (122), is more complex than cursory examination... 

Biosynthesis of the ergot bases involves an N-methylation step and it has been shown that the N-methyl group arises intact from methionine. It is as yet unknown, however, at which stage the methylation occurs but since iV-methyl-tryptophan and iV-methyltryptamine are not intermediates, the reaction must occur at a stage between (118) and chanoclavine-I (119). The failure of radioactive A -demethylchanoclavine-1 (or N-demethylchanoclavine-II) to label elymoclavine (123) in Claviceps cultures indicates that iV-methylation occurs before formation of the chanoclavine skeleton. 

This section of the chapter will describe alkaloids identified in fungal strains that are biosynthetically related to ergot alkaloids. These compounds carry a modified ergoline scaffold like epoxyagroclavine-I (168) or even an obviously different skeleton like aurantioclavine (176) (Fig. 4.10) (88, 91,117). 

In some cases, lysergic acid is produced by alkaline hydrolysis of peptide ergot alkaloids or lysergic acid derivatives. Harsh conditions of this chemical reaction cause a drop in the yields due to decomposition of ergoline skeleton. This could be another challenge for a further search for bioconversion methods. 

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