Ergotic process

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. 

Hindmarch I, Parrott AC and Lanza M (1979). The effects of ergot alkaloid derivative (Hydergine) on aspects of psychomotor performance, arousal, and cognitive processing ability. Journal of Clinical Pharmacology, 19, 726-732. 

Alkaloids of this group are susceptible to oxidative biotransformations by many microorganisms resulting in N-demethylation, C-hydroxylation, or ring-closure reactions (11). Many of the observed biotransformations parallel or are closely related to processes thought to occur in the normal biosynthesis of the ergot alkaloids and may indeed involve the same or similar enzyme systems to those responsible for the normal production of the alkaloids themselves (11, 64, 65). 

We end this section with a synthesis of N-acetyl clavicipitic acid methyl ester, an ergot alkaloid, by Hegedus. The power of orga no-transition-metal chemistry is illustrated in five steps of this seven-step process. Each of the organometallic steps catalysed by Pd(0) or Pd(II) has been described in this chapter. The overall yield is 18%, a good result for a molecule of such complexity. 

A number of alkaloids are known whose structures are more or less similar to those of endogenous neurotransmitters. Targets can be the receptor itself, the enzymes which deactivate neurotransmitters, or transport processes, which are important for the storage of the neurotransmitters in synaptic vesicles. Alkaloids relevant here include (Table IV) brucine, ergot alkaloids, eseridine, serotonin, physostigmine, gelsemine, j8-carboline alkaloids, strychnine, yohimbine, berberine, bicuculline, bul-bocapnine, columbamine, coptisine, coralyne, corlumine, ephedrine, ga-... 

The next target is the gestation process itself. As outlined above, a number of alkaloids are mutagenic and lead to malformation of the offspring or directly to the death of the embryo (Table V). The last step would be the premature abortion of the embryo. This dramatic activity has been reported for a number of allelochemicals, such as mono- and sesquiterpenes and alkaloids. Some alkaloids achieve this by the induction of uterine contraction, such as the ergot and lupine alkaloids (312). 

Scheme 8. Biosynthesis of ergot alkaloids. Selective inhibition of DMAT-synthase in the biosynthesis pathwayby 5-fluorotryptophan blocks synthesis of alkaloids de novo but does not influence other biochemical processes in the cells, e. g., transfructosylating enzymes [27]...

Until now no process was known which allows the physiologically practically inactive lysergic acid to be linked with a basic residue, such as an amino-alcohol or an amino acid, in order to prepare compounds of the type of ergot alkaloids. This was primarily due to the fact that lysergic acid was very difficult to prepare, as it was only obtainable as a degradation product from ergot alkaloids and because its constitution was unknown. 

As compared to the known alkaloids of the ergot group which possess an action on the uterus and on the sympathetic branch of the vegetative or autonomic nervous system the new alkaloid prepared according to the present process has a specific action in very small doses of 20—50 ug. on the central nervous system. 

---