Preparation of Ergot Alkaloids

Example V The figures relating to a control culture have here been omitted since the comparative results are substantially equivalent to those obtained in nitrogen and phosphate deficiency tests. The example therefore merely gives a substrate upon which, in conditions similar to those already described in the foregoing examples, a total of 36.2 mg. percent of alkaloids (calculated on the basis of ergometrine) was obtained from surface cultures at the end of 25 days. 

The present invention relates to the production of ergot alkaloids, especially of ergometrine and of ergotoxine of high ergocristine content by biosynthesis more particularly it provides a process for the preparation of such ergot alkaloids by cultivating a specific strain of Claviceps purpurea on a synthetic nutrient medium. 

6 Litres of a nutrient medium of the composition given below were charged into an aerated laboratory fermenter of 10 litres capacity, equipped with a stirring device  

The pH-value of the medium was adjusted with aqueous ammo- 

The culture (300 L.) was transferred into 3000 litres of a nutrient medium of the following composition in an acid-resistant fermenter of 5 m3 capacity  

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Dinitro-ll-oxatricyclo[6.2.1.01,6]undec-9-ene has been prepared by an intramolecular Diels-Alder reaction of the furan with a nitroalkene group as shown in Eq. 8.26. This tricyclic compound is a versatile synthetic tool for the preparation of ergot alkaloids.41... 

The present invention relates to the manufacture, separation and preparation of ergot-alkaloids in state of high purity, by subjecting mixtures of the very sensitive ergot-alkaloids to chromatographic adsorption analysis. 

Another object of the present invention is the use of the chromatographic adsorption process for the preparation of ergot-alkaloids in pure state. 

Richter Gedeon Vegyeszeti Gyar R.T. Preparation of Ergot Alkaloids 1967 GB 1,064,764... 

Wack, G. Nagy, L. Szekely, D. Szolnoky, J. Udvardy-Nagy, E. Zsoka, E. Fermentation Process for the Preparation of Ergot Alkaloids 1975 US 3,884,762... 

The possibility of carrying out quantitative stability tests on aqueous preparations of ergot alkaloids, using TLC, has also been reported [85,178] reference may be made too to the semi-quantitative detection of free nicotinic acid in polyvitamin preparations containing nicotinamide [113]. 

The Madelung indole synthesis has been employed in the preparation of some complex indole systems. Uhle et al. reported the conversion of N-formyl-5,6,7,8-tetrahydronaphthylamine 28 into 1,3,4,5-tetrahydrobenz[c,ti]indole 29 with t-BuOK in 11% yield in regard to synthesis of ergot alkaloids. ... 

An entirely different approach to 3-haloindoles involves a mercuration/iodination sequence, which has been adopted by Hegedus to prepare 4-bromo-3-iodo-l-(4-toluenesulfonyl)indole for use in the synthesis of ergot alkaloids [20,21], We will discuss this chemistry later. 

Glycosides of ergot alkaloids were isolated as naturally occurring products [40] and a large series of them has been prepared by chemical and enzymatic methods [41]. 

A series of other glycosides of ergot alkaloids was prepared by enzymatic transglycosylations using activated p-nitrophenylglycosides as donors [47]. 

Recently, a large series of glycosides of ergot alkaloids was prepared using both chemical and enzymatic methods [131,132,133,134]. Preliminary results obtained indicate that some of these derivatives could have very interesting activities compared to their aglycons. 

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. 

One object of the present invention is, therefore, a process for the manufacture, separation and preparation of pure ergot-alkaloids, consisting in subjecting raw or pure mixtures of ergot alkaloids or impure ergot-alkaloids to the chromatographic adsorption process. 

That the methods of culturing ergot in vitro described in the literature have not so far led to the successful production of ergot alkaloids on a preparative scale is convincingly demonstrated by the fact that the ergot employed for the manufacture of the active principles... 

Epileptic seizures treatment of Erectile dysfunction treatment of Ergot alkaloids Estrogenic preparations... 

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