Ergots

—It is now clear that the peptidic moiety of ergot alkaloids like ergotamine 

L-Valyl-L-valyl-L-proline was incorporated into ergocornine (135) only after breakdown into its constituent amino-acids/ These negative results have led to the suggestion that formation of the peptidic fragment and linkage with lysergic acid occurs on a multi-enzyme complex so that at no stage are there any free peptidic intermediates. 

Dimethylallyltryptophan (139) has been identified as the first intermediate after tryptophan in ergot alkaloid biosynthesis.In experiments with a Claviceps species, clavicipitic acid (140) was identified as a major product formed from (139).(The enzyme catalysing this transformation was identified in both the supernatant and microsonal fractions oxygen is necessary for the reaction but cytochrome P-450 does not appear to be involved.) But radioactive clavicipitic acid was found to be a much less efficient precursor than (139) for elymoclavine and thus is in all probability not an intermediate in ergot alkaloid biosynthesis. 

Biochem. Biophys., 1968, 126, 967 S. Agurell and J.-E. Lindgren, Tetrahedron Letters, 1968, 5127  

—Experiments directed towards solving the outstanding problem of the biosynthesis of the peptide lysergic acid derivatives from lysergic acid have not yet proved definitive, and the recent results for ergotamine and ergometrine represent little advance on those reviewed previously. 

Marekov, M. Arnaudov, and St. Popov, Doklady Bolg. Akad. Nauk., 1970, 23, 169. D. C. Wigfield, B. Lem, and V. Srinivasan, Tetrahedron Letters, 1972, 2659. 

DL-[l- C]Valine, D-, L-, and DL-fl- CJalanine, and lysergylvaline (31 label as shown) have been studied as precursors for ergocornine (32) and ergo-cryptine (33), examined mostly as the 3 1 mixture ergotoxine. L-Alanine and 

Basmadjian, H. G. Floss, D. Grdger, and D. Erge, Chem. Comm., 1969, 418. 

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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. 

The disease takes two different forms depending apparently on whether ergotoxia, the alkaloid ia ergot, attacks predomiaantiy the aervous or the circulatory system. The former coaditioa is characterized by severe coavulsive seizures the latter produces an iatense burning and itching of the skin called St. Anthony s Fire. 

There are currently two medicinally valuable alkaloids of commercial import obtained from ergot. Commercial production involves generation parasiticaHy on rye in the field or production in culture because a commercially useful synthesis is unavailable. The common technique today (65) is to grow the fungus in submerged culture. Clavicepspaspali (Stevens and Hall) is said to be more productive than C. purpurea (Fries). In this way, ergotamine (100,... 

Several chemical compounds may cause inflammation or constriction of the blood vessel wall (vasoconstriction). Ergot alkaloids at high doses cause constriction and thickening of the vessel wall. Allylamine may also induce constriction of coronary arteries, thickening of their smooth muscle walls, and a disease state that corresponds to coronary heart disease. The culprit is a toxic reactive metabolite of allylamine, acrolein, that binds covalently to nucleophilic groups of proteins and nucleic acids in the cardiac myocytes. 

For the detection of the ergot alkaloids 0.2 g o-phthalaldehyde in 100 ml cone, sulfuric acid ( ) [15] or buffer solution is employed as spray solution. Cysteine [11, 12, 15, 19] or sulfurous acid [17] is occasionally substituted for mercapto-ethanol. 

Poisoning by ergot still occurs occasionally in countries where rye is extensively used as a food grain or where ergotised grain is liable to be fed to cattle and methods for its detection have been devised, but interest in the analysis of ergot centres chiefly on the estimation of the active alkaloids in the crude drug or its preparations. The methods used may... 

For detailed information on ergot the late Professor G. Barger s monograph 11931) should be consulted. ... 

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. 

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