Ergoline skeleton

A Messina, AM Girelli, M Flieger, M Sinibaldi, P Sedmera, L Cvak. Direct resolution of optically active isomers on chiral packings containing ergoline skeletons. 5. Enantioseparation of amino acid derivatives. Anal Chem 68 1191-1196, 1996. 

Similarly, irradiation of the tricyclic enamide 226 for over 96 hr afforded the lactam 227, in 42% yield, which was reduced with LAH and then acetylated to give the compound 228, with an ergoline skeleton in good yield. This method provided a simple route for constructing the clavine skeleton (130) (Scheme 86). 

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... 

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

En route to a new synthesis of the ergoline skeleton, Parker and colleagues developed a new cyclization of 4-unsubstituted indoles. Indole 235 was reduced to a mixture of indoline epimers under standard triethylsilane/ trifluoroacetic acid conditions proteaion of indoline 236 with benzoyl chloride delivered 237 in 85% yield over two steps. Finally, palladium-catalyzed cyclization afforded desired tetracyclic indole structure 238 in 86% yield (130L2598). 

The pharmacodynamically complex profile of the ergolines as ligands for serotonin (5-HT) receptors, dopamine (D) receptors, and adrenoceptors, respectively, is explainable by the fact that these alkaloids include the essential structural features of the corresponding three monoamine neurotransmitters. This can be visualized by superimposition of the ergoline skeleton by these three natural agonists each (Fig. 4.9). 

Table 3 Alkaloids with modified ergoline skeleton...

Preparation of radiolabelled derivatives is also reviewed here. Total syntheses of the ergoline skeleton are not included, but they have been treated in a recent monograph (Ninomiya and Kiguchi, 1990). 

Chemical modifications of individual positions of the ergoline skeleton (Fignre... 

Position 2 of the ergoline skeleton is highly suitable for synthetic modification of EA by both electrophilic and radical substitution. Many modifications have been reviewed by Rutschmann and Stadler (1978) chlorination, bromination and iodination, nitration and reduction of nitro derivatives to amino derivatives and reaction with 2-methoxy-l, 3-dithiolane affording an intermediate which can be desulfurised to a 2-methyl derivative. Troxler and Hofmann (1959) described the oxidation of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy-2, 3-dihydrolysergic acid diethylamide. 

Figure 5 Oxidative cleavage of 1, 2-bond of ergoline skeleton and the use of the...

These positions on the aromatic part of the ergoline skeleton are accessible to electrophilic substitution. The most reactive position for electrophilic substitution is position 2, less reactive is position 13. Positions 14 and 12 are substituted only under harsh conditions when usually complicated mixtures of products are obtained or some special techniques must be used. 

Whereas the structure-activity relationship was the main target of synthetic modification of the ergoline skeleton, syntheses with labelled compounds were aimed at obtaining identical molecules using suitable labelled intermediates. In... 

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. 

A. Tandem Radical Cyclization for the Construction of the Ergoline Skeleton... 

Cocyclization of 4-ethynyl-3-indoleacetonitrile with an alkyne in the presence of a cupric complex gave rise to the ergoline skeleton, which was converted into lysergic acid diethylamide as discussed in Section 111, C. 

Structurally closely related to LSD, Lisuride (226) is a compound having a 3,3-dimethylureido substituent, at die 9-position of the ergoline skeleton, and was first prepared in 1960 as a dopamine Dj-receptor agonist (98). Lisuride, as its acid maleate, is commercially available under Ae names of Cuvalit, Dopergin, Eunal, or Lysenyl, and is used clinically as an antimigraine and also as a prolactin inhibitor. The pharmacological activi and toxicity of lisuride were... 

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