Lysergic acid derivatives peptide alkaloids

Biosynthesis. In Claviceps purpurea, and presumably also in higher plants, E.a. are biosynthesized from tryptophan and isopentenylpyrophosphate (see Terpenes). Synthesis proceeds via 4-dimethylallyl-tiyptophan, which is converted into the alkaloid chanoclavine (by hydroxylation, methylation, decarboxylation and formation of a new C-C bond). All the other clavine alkaloids and the lysergic acid derivatives are derived from chanoclavine. The peptide moieties of the ergotamine and ergotoxin alkaloids are formed by a multienzyme complex (Fig. 2). E.a. are prepared from the sclerotia of rye, previously inoculated with Claviceps and they are also produced by culture of the fungus on artificial growth media. 

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. 

The delicacy of the hitherto only synthetic pathway to the peptide alkaloids of lysergic acid is also underlined by the fact that other authors had failed to circumvent it (37). The main difficulty lies in the rapid epimerization of the L-proline containing intermediates to the d-proline isomers and the inherent instability of functionalized a-hydroxy-a-amino acid derivatives. 

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. 

The peptidic ergot alkaloids, e.g. ergocornine (139), derive by combination of three appropriate a-amino-acids with lysergic acid (134). The sequence by which the individual units become linked is, however, obscure. There is some evidence for linkage between a cyclic dipeptide and a lysergyl amino-acid... 

Elymoclavine is the biosynthetic precursor of paspaHc acid, which is further isomerised to lysergic acid. Lysergic acid can be transformed to its derivatives simple amides and more complex derivatives—alkaloids of peptidic type. Lysergic... 

---