Advances in Biochemical Engineering/
Biotechnology, Vol. 68
Managing Editor: Th. Scheper
© Springer-Verlag Berlin Heidelberg 2000
Progress and Prospects of Ergot Alkaloid Research
Joydeep Mukherjee, Miriam Menge
Institut für Technische Chemie, Universität Hannover, Callinstr. 3, D-30167 Hannover,
Germany
E-mail: mukherjee@mbox.iftc.uni-hannover.de
Ergot alkaloids, produced by the plant parasitic fungi Claviceps purpurea are important
pharmaceuticals. The chemistry, biosynthesis, bioconversions, physiological controls, and
biochemistry have been extensively reviewed by earlier authors. We present here the research
done on the organic synthesis of the ergot alkaloids during the past two decades. Our aim is
to apply this knowledge to the synthesis of novel synthons and thus obtain new molecules by
directed biosynthesis. The synthesis of clavine alkaloids, lysergic acid derivatives, the use of
tryptophan as the starting material, the chemistry of 1,3,4,5-tetrahydrobenzo[cd]indoles, and
the structure activity relationships for ergot alkaloids have been discussed. Recent advances
in the molecular biology and enzymology of the fungus are also mentioned. Application of
oxygen vectors and mathematical modeling in the large scale production of the alkaloids are
also discussed. Finally, the review gives an overview of the use of modern analytical methods
such as capillary electrophoresis and two-dimensional fluorescence spectroscopy.
Keywords. Ergot, Alkaloid synthesis, Claviceps, Directed biosynthesis, Bioreactors
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2
Chemistry, Bioconversions, and Directed Biosynthesis . . . . . . 2
2.1
Chemical Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1.1 Chemical Structures . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1.1.1 Clavine Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1.1.2 Simple Lysergic Acid Derivatives . . . . . . . . . . . . . . . . . . . 4
2.1.1.3 Ergopeptines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.1.1.4 Ergopeptams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.1.2 Synthesis of Clavine Alkaloids and Lysergic Acid Derivatives . . . 5
2.1.3 Use of Tryptophan as the Starting Material . . . . . . . . . . . . . 7
2.1.4 1,3,4,5-Tetrahydrobenzo[cd]indoles . . . . . . . . . . . . . . . . . 7
2.1.5 Structure Activity Relationships . . . . . . . . . . . . . . . . . . . 8
2.2
Bioconversions of Ergot Alkaloids . . . . . . . . . . . . . . . . . . 10
2.3
Directed Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . 10
3
Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
4
Fermentation Technology . . . . . . . . . . . . . . . . . . . . . . . 13
5
Analytical Methods . . . . . . . . . . . . . . . . . . . . . . . . . . 16
6
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18