0000000000590328
AUTHOR
Reinhold Sieben
Clavines as antitumor agents. 3: Cytostatic activity and structure/activity relationships of 1-alkyl agroclavines and 6-alkyl 6-noragroclavines.
The cytostatic potential of twenty antibiotic agroclavines has been examined in the L5178y mouse lymphoma cell system. Twelve of these compounds are described for the first time. It is shown that the substituent at N-1 of agroclavine is very important whereas the substituent at N-6 is of less influence if it is not hydrogen. Incorporation studies in the presence of 1-propylagroclavine suggest that DNA synthesis in the lymphoma cells is inhibited. The effect on the corresponding [3H]thymidine incorporation in murine spleen lymphocytes is comparably low. Neither a significant change of mRNA efflux nor of DNA polymerase alpha and beta activities was caused. The mechanism of action seems to be …
Partialsynthese neuer Ergolinderivate aus Clavinalkaloiden, 4. Mitt. N-1-, C-2- und N-6-monosubstituierte Agroclavine
Agroclavin (1) wird in flussigem Ammoniak/Kaliumamid mit Alkyliodid am Indolstickstoff alkyliert. 1 last sich mit N-Iodsuccinimid zu 2-Iod-1 (3) umsetzen. Mit der Bromcyan-Methode wird 6-Nor-1 (4b) gewonnen und danach an N-6 alkyliert. Partial Synthesis of New Ergoline Derivatives from Clavine Alkaloids, IV: Agroclavines Monosubstituted at N-1, C-2, and N-6 Agroclavine (1) is alkylated at the indole nitrogen with alkyl iodide in ammonia/potassium amide. It is convertible to 2-iodo-1 (3) with N-iodosuccinimide. Compound 6-nor-1 can be prepared by means of the cyanogen bromide method; alkylation at N-6 is described exemplarily for the ethyl derivative.