2.2
Bioconversions of Ergot Alkaloids
Bioconversions of ergot alkaloids have been excellently reviewed [5]. In his
article the author has discussed clavine bioconversions, bioconversions of
lysergic acid derivatives, bioconversion as a tool to study the metabolism of
ergot alkaloids in mammals, and finally the use of immobilization in ergot
alkaloid bioconversion. We will look into developments after this period.
Chemical oxidations yield complex and inseparable product mixtures.
Oxidative biotransformations can thus be a substitute for the intricate ergot
alkaloid molecules. The discovery of elymoclavine-O-b-d-fructoside, elymoclavine-O-b-d-fructofuranosyl(2-1)-O-b-d-fructofuranoside, and chanoclavine
fructosides revealed a new group of naturally occurring ergot alkaloids, the
ergot alkaloid glycosides. By conversion from their aglycones, the respective
fructosides of chanoclavine, lysergol, and dihydrolysergol were obtained [5].
Presence of the fructosyl residue in the molecule, however, does not lead to any
interesting biological activities. Incorporation of the b-galactosyl moiety in the
ergot alkaloids might create new pharmacologically useful compounds. With
this objective, b-galactosides of elymoclavine, chanoclavine, lysergol, 9,10-dihydrolysergol, and ergometrine were prepared using b-galactosidase from
Aspergillus oryzae [62]. The effect of the galactosides on human lymphocytes
was tested for their natural killer (NK) activity against a NK-sensitive target
cell. The galactosides of the three compounds had stimulatory effects which
appeared to be dose dependent.
Ergot alkaloid O-glycosides, ergot alkaloid N-glycosides, and biological
activity of new ergot alkaloid glycosides have been recently reviewed [1].
Agroclavine and elymoclavine were modified using plant cell cultures exhibiting high peroxidase activity. Setoclavine and isosetoclavine were obtained
from the media after transformation of agroclavine on a semipreparative scale.
Similar treatment of elymoclavine produced 10-hydroxyelymoclavine [63]. A
new spiro-oxa dimer of lysergene was isolated as a product of the biotransformation of lysergene by Euphorbia calyptrata suspension cell culture [64].
Structures of oxepino[5,4,3-c,d]indole derivatives and 3,4-disubstituted indoles, end products from the biotransformation of chanoclavine by Euphorbia
calyptrata cell culture, have been elucidated by NMR and mass spectroscopy
[65]. The stereoselective oxidation of agroclavine by haloperoxidase from
Streptomyces aureofaciens was reported [66].
2.3
Directed Biosynthesis
Directed biosynthesis is a possible method for the synthesis of new ergot
alkaloid molecules and for probing the biosynthetic pathway by feeding
Claviceps spp. with natural and unnatural amino acids and synthetic precursors.
In order to test the possible involvement of free tripeptide intermediates
l-valyl-(114 C)-l-valyl-l-proline was synthesized [67], which was fed to cultu10
J. Mukherjee · M. Menge
Bioconversions of Ergot Alkaloids
Bioconversions of ergot alkaloids have been excellently reviewed [5]. In his
article the author has discussed clavine bioconversions, bioconversions of
lysergic acid derivatives, bioconversion as a tool to study the metabolism of
ergot alkaloids in mammals, and finally the use of immobilization in ergot
alkaloid bioconversion. We will look into developments after this period.
Chemical oxidations yield complex and inseparable product mixtures.
Oxidative biotransformations can thus be a substitute for the intricate ergot
alkaloid molecules. The discovery of elymoclavine-O-b-d-fructoside, elymoclavine-O-b-d-fructofuranosyl(2-1)-O-b-d-fructofuranoside, and chanoclavine
fructosides revealed a new group of naturally occurring ergot alkaloids, the
ergot alkaloid glycosides. By conversion from their aglycones, the respective
fructosides of chanoclavine, lysergol, and dihydrolysergol were obtained [5].
Presence of the fructosyl residue in the molecule, however, does not lead to any
interesting biological activities. Incorporation of the b-galactosyl moiety in the
ergot alkaloids might create new pharmacologically useful compounds. With
this objective, b-galactosides of elymoclavine, chanoclavine, lysergol, 9,10-dihydrolysergol, and ergometrine were prepared using b-galactosidase from
Aspergillus oryzae [62]. The effect of the galactosides on human lymphocytes
was tested for their natural killer (NK) activity against a NK-sensitive target
cell. The galactosides of the three compounds had stimulatory effects which
appeared to be dose dependent.
Ergot alkaloid O-glycosides, ergot alkaloid N-glycosides, and biological
activity of new ergot alkaloid glycosides have been recently reviewed [1].
Agroclavine and elymoclavine were modified using plant cell cultures exhibiting high peroxidase activity. Setoclavine and isosetoclavine were obtained
from the media after transformation of agroclavine on a semipreparative scale.
Similar treatment of elymoclavine produced 10-hydroxyelymoclavine [63]. A
new spiro-oxa dimer of lysergene was isolated as a product of the biotransformation of lysergene by Euphorbia calyptrata suspension cell culture [64].
Structures of oxepino[5,4,3-c,d]indole derivatives and 3,4-disubstituted indoles, end products from the biotransformation of chanoclavine by Euphorbia
calyptrata cell culture, have been elucidated by NMR and mass spectroscopy
[65]. The stereoselective oxidation of agroclavine by haloperoxidase from
Streptomyces aureofaciens was reported [66].
2.3
Directed Biosynthesis
Directed biosynthesis is a possible method for the synthesis of new ergot
alkaloid molecules and for probing the biosynthetic pathway by feeding
Claviceps spp. with natural and unnatural amino acids and synthetic precursors.
In order to test the possible involvement of free tripeptide intermediates
l-valyl-(114 C)-l-valyl-l-proline was synthesized [67], which was fed to cultu10
J. Mukherjee · M. Menge