Ergot bases

Hordenine is the name of the related base present in the germs of barley, Hordeum vulgare. It has been proven to have the constitution of a di-methyl derivative of the ergot base, as above. 

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. 

These aqueous solutions, when rendered alkaline with ammonia or sodium carbonate (sodium hydroxide when phenolic alkaloids are known to be absent), may yield the basic constituents in filterable form. However, experience has shown that it is more convenient to recover these by extraction with ether or chloroform. Chloroform is to be preferred for it extracts all alkaloids except the quaternary bases (curine), which in any case must be recovered in the form of an insoluble complex salt. This procedure fails when the alkaloids are unstable under the conditions of the experiment, and is conspicuously unsuccessful mth the ergot bases. It is also probable that some alkamine esters suffer change under the conditions imposed. 

Lysergic acid (7.55), formed from elymoclavine (7.55), is a precursor for a range of peptidic ergot bases, e.g. ergotamine (7.59). 

A base, formed by the bacterial degradation of histidine, and present in ergot and in many animal tissues, where it is liberated in response to injury and to antigen-antibody reactions. If injected it causes a condition of shock with dilatation of many blood vessels, loss of plasma from the capillaries to the tissues and a rapid fall in blood pressure. It is normally prepared from protein degradation products. 

Isolation of Ergot Alkaloids. In the papers already quoted (refs. 6 to 19) the processes used for the isolation of the total alkaloids and the separation of the component bases are given to those may be added references to methods by other authors. There are also numerous patented processes, some of which are quoted in the following special sections. 

Stoll, Hofmann and Petrzilka (1946) have also succeeded in obtaining dihydro-derivatives of this series (ergotinine type) of ergot alkaloids. Each of these bases yields two dihydro-derivatives, distinguished as isomerides I and II. Their chief characteristics are siunmarised in the following table —... 

Transformation of bromocriptine free base 2 into water soluble salt -mesylate, is the only way to obtain a suitable therapeutical form. Crystallization of mesylate using alcohol as a solvent in the presence of excess of strong acid, e.g. methanesulphonic acid can induce formation of 12 -0-alkyl-derivative 2. Until now this derivatisation of ergot molecule has been practically unknown. In continuation we developed the preparative method for obtaining these compounds, (using tetrafluoroboric acid as a catalyst) (ref. 20). 

FIGURE 5 Effect of methanol concentration on the chiral resolution of ergot alkaloid on terguride-based CSP using 0.05 M ammonium acetate as the mobile phase at pH 7.2 (A),... 

Ergot Alkaloids.—4-(yy-Dimethylallyl)tryptophan (122) is the first intermediate beyond tryptophan in ergot alkaloid biosynthesis. Chanoclavine-I (127) is the first tricyclic base (cf. Vol. 10, p. 26, and ref. 2). Recently, (124 labels as shown) has been found to be a very efficient and intact precursor for elymoclavine (128).45 The high level of incorporation indicates that (123) is a probable intermediate situated between (122) and (127). The decarboxylation product (125) was not utilized for biosynthesis, so, although decarboxylation of (123) is required for the conversion of (123) into (127), either it is intimately associated with ring-closure or an imine that is related to (126) is involved. 

A hypothetical sequence, based mainly on the reported isolation of cMvsergyl-L-valine methyl ester from rye ergot (18) was proposed by Agurell (58). According to him, the biogenesis of ergotamine (68) can be represented as follows ... 

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