Clavin alkaloids

For example, ergot alkaloids produce without exception blue chromatogram zones, while clavine alkaloids primarily produce green colors [4], Urea derivatives and primary aromatic amines yield yellow chromatogram zones [28,33,34,36,37] and PR toxin and PR imine emit intense blue fluorescence on excitation with long-wavelength UV light (X = 365 nm) [44],... 

Citrinine la 69,147,148 Citronellal la 158,159 CitroneUol la 68-70,327 Citronellyl acetate la 68 Claisen-Tischenko reaction 15 54 Clathrate complex 15 303 Clavin alkaloids 15 243 Clavine alkaloids 15 246,252 Cleanup la 119 Clemastin 15 354 Clenbuterol 15 106,107,354 Clobutinol 15 354 Cloforex 15 194,296 Clomethiazole lb 354 Clomipramine 15 352,354,355 Clonacillin lb 301 Clonidine 15 354 Clopamide 15 354 Clorexolon 15321 Clotrimazol 15 98,99,401,402 Cloxacillin 1584,188 Clozapin 15 354 Cnicin 15 290... 

Die Clavin-Alkaloide kommen besonders in Sklerotien verschiedener Claviceps-S cvts vor, die auf femostlichcn und afrikanischen Grasem parasitieren. Saprophytische Kulturen dieser Pilze bilden ebenfalls diese einfachen Ergolin-Dcrivatc. In Spuren sind sie auch in Sklerotien und saprophytischen Kulturen von Claviceps purpurea nachgewiesen worden. 

Da es auch gelungen ist, die spater zu besprechenden Clavine sterisch mit der Lysergsaurc zu verknupfen, ist auch die absolute Konfiguration der Clavin-Alkaloide gesichert. 

Tatsachlich konnte diese Arbeitsgruppe zeigen, daB Mevalonsaure in Clavin-Alkaloide 38) inkorporiert wird. Das ist der erstc experimentcUe Beweis uberhaupt, daB Mevalonsaure nicht nur eine Vorstufe fur typi-... 

Spilsbury, J. F., and S. Wilkinson The Isolation of Festuclavine and Two New Clavine Alkaloids from Aspergillus Fumigatus Fres. J. chem. Soc. [London] 1961, 2085. 

In an approach to the clavine alkaloids [170] based on intramolecular nitrone-alkene cycloaddition, the condensed tetracyclic system is probably favored by steric factors. Equilibration at higher temperature leads to predominantly a bridged oxabicyclo-[3.2.1]nonae derivative in which a portion of the molecule contains polarity alternation sequence (OCOC=0, N-C-C-C=0). 

The unusual structure of cycloclavine as the first known pentacyclic clavine alkaloid was derived from physical data (mass spectrum M+ 238 NMR signals of the cyclopropyl methylene group = 0.46 and 1.60) and some chemical transformations (hydrogenation, reductive ring opening, and quaternization). The remaining details of its constitution were finally determined by an X-ray analysis of the metho-bromide. Thus it was shown that the chirality of 11 is 5B, 8R, 10R. 

To begin with the more classic transformations, the total synthesis of a clavine alkaloid, (+ )-isosetoclavine (24) reported by Kornfeld and Bach (27) deserves mention. Using the same tetracyclic ketone (23) as starting material as in their famous synthesis (28) of lysergic acid (43) (cf. Vol. VIII) 24 was built up stereospecifically in two steps as demonstrated below. 

It had already been stated earlier that clavine alkaloids are formed from L-tryptophan and mevalonic acid, the methyl group in position 6 originating from methionine (53, 54). There was also evidence that 4-dimethylallyltryptophan (3) is an early intermediate in the biosynthetic pathway (58). 

In his thorough review (385 references), Voigt (55-57) covers the literature up to 1967. The article also comprises microbiological aspects of alkaloid synthesis in saprophytic cultures as well as in vivo studies. Biogenetic interrelationships between different species of clavine alkaloids apart from the main pathway are also discussed there. 

Hydroxylation of clavine alkaloids in vitro can be brought about by horseradish peroxidase using hydrogen peroxide as the oxidant, and numerous other tissues (70). This leads only to 8-hydroxylation, e.g., no elymoclavine (54) can be detected from 53. On the other hand, this hydroxylation step also occurs in ergot as a minor metabolic pathway, but it will not be considered here in detail. The reader is referred to the review articles of Voigt (55-57) and of Ramstad (70). 

On the basis of their structural differences, the ergot alkaloids may be divided into two main groups one group to include all lysergic acid derivatives of the acid amide type, and the other to include the so-called clavine alkaloids. Further structural groups may be recognized within these main groups, as is shown by Tables I and II. 

Recently, with the aid of the new, efficient methods of detection, e.g., paper and thin-layer chromatography, clavine alkaloids have also been found to occur in ergot obtained from rye. Furthermore, in 1960, Hofmann and Tscherter surprisingly found the occurrence of alkaloids of the clavine type in higher plants, i.e., in genera of the family of twining plants (Convolvulaceae) (70, 71). 

Table IV (p. 764) contains chemical and physical data and indications on the source of the clavine alkaloids.

In saprophytic cultures of the Pennisetum ergot fungus, only tryptophan, deuterated in the 5 or 6 position, was used for the synthesis of the clavine alkaloids without loss of the deuterium. Deuterium in the 4 position was lost. These experiments showed that the hypotheses, according to which 5-hydroxytryptophan would be an intermediate stage in the biosyntheses (126, 127), could not be correct (128). 

All ergot alkaloids which have so far been used therapeutically are lysergic acid derivatives. Representatives of the second main group, the clavine alkaloids, have also been found to be pharmacodynamically active, but as yet, none has been found to exert effects that can be utilized in therapy. The uterotonic and sympatholytic actions are less prominent in their pharmacological spectra of activity but, for example, elymoclavine and agroclavine have a pronounced central excitatory action which is attributed to their stimulation of sympathetic centers (172). 

Besides their activity mediated by neurotransmitter receptors, clavine alkaloids also possess antibiotic and cytostatic activities. The antibiotic activity of EA was ascribed to inhibition of nucleic acid replicatory processes [32]. The antineo-plastic and antiviral activity of various heterocycles could be augmented by their N-ribosylation. The preparation of N-ribosides of EA could form analogous compounds to nucleosides with the aglycon possessing both neuro-humoral and cytostatic activity. 

The ergot alkaloids can be divided into two main groups the lysergic acid alkaloids and the clavine alkaloids. The analytical problems concerning the lysergic acid alkaloids can be summarized as follows ... 

HPLC analysis of clavine alkaloids has been carried out by Wurst et al 57,58... 

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