Peptides from ergot alkaloids

Since the last review on ergot alkaloids, important new alkaloids from different sources, mostly from new ergot strains, have been discovered. Their proposed structure could in some cases be confirmed by synthesis. Some of them seem to be intermediates in the biogenetic pathway from tryptophan to the peptide alkaloids. Others are considered as end products of secondary plant metabolism. In any case we find many interesting structures among these recently discovered substances. 

The majority of alkaloids produced from ergot fungi are peptides of lysergic acid. Upon hydrolysis they decompose to give lysergic acid, two... 

Cleavage Products Resulting from Hydrolytic Degradation of Ergot Alkaloids of the Peptide Type... 

The biosynthesis of the ergot alkaloids involves condensation of dimethyl-allyl pyrophosphate (derived from mevalonic acid) with tryptophan. Closure of the C- and D-rings of the alkaloid involves specific hydroxylations by cytochrome P450-dependent oxidases and rearrangements. Further modifications involve N-methylation in the presence of S-adenosyl methionine and/or condensation with amino acids and peptides. Coupling of lysergyl CoA with certain peptides forms the peptide alkaloids which are the most bioactive of the ergot alkaloids. 

The biosynthetic pathway to the ergoline nucleus proceeds through 4-dimethylallyl tryptophan (4-DMAT), chanoclavine-I, agroclavine, and lysergic acid. Two cis, trans isomerizations occur one before chanocla-vine-I and the other before agroclavine, as shown by experiments with [2- C]-mevalonic acid and [Z-CH3]-4-DMAT (Fig. 36). The peptide unit is derived from a combination of three amino acids, one of which is always proline. Several genera in the plant family Convolvulaceae Rivea, Ipomoea, etc.) also produce ergot alkaloids. 

Ergohexine (80) and ergoheptine (81) are two new ergot alkaloids which contain L-homoleucine in the peptide unit, an amino-acid not previously encountered in the natural alkaloids the diketopiperazine derivative (82) containing the same amino-acid was also isolated from the fungus. ... 

As shown, a considerable part of the modern separation methods of amino acids and peptides originated in Max Bergmann s laboratory at the Rockefeller Institute. A different separation technique was introduced in the same institute at the same time by Lyman C. Craig, in the laboratory of J.A. Jacobs. Here, from 1933, he worked on ergot alkaloids developing a lasting interest in separation techniques. The well-known method of extraction of substances from an aqueous into a non-water-miscible phase like chloroform or vice versa was systematically elaborated by him to a multiple extraction and re-extraction procedure, countercurrent distribution [25]. By this method, performed in a specially... 

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