Preparation and properties of formycin analogues methylated on the pyrazolo ring nitrogens and/or the ribose cis-hydroxyls.
1. Diazomethane treatment of formycin A in the presence or absence of SnCl2 as catalyst, was used for the preparation of the 2'-O-methyl, 3'-O-methyl, N1-methyl and N2-methyl derivatives. The four possible dimethylated derivatives, 2'(3")-O,N1(N2)-dimethylformycins, were obtained by controlled treatment of formycin with diazomethane in the presence of SnCl2, and subsequent column chromatography for product isolation. 2. All the foregoing products were characterized and identified by chromatography, ultraviolet absorption spectra, and proton magnetic resonance spectroscopy. Extensive u.v. spectral data, and spectrally determined pK values, for the various derivatives are presented. 3. N2-Methylformycin B was also prepared by enzymatic deamination of the parent N2-methylformycin A. 4. The sequence of elution of N1-methylformycin and N2-methylformycin on a strongly basic ion exchange column suggested that the latter is in the syn conformation. The susceptibility of N2-methylformycin to adenosine deaminase shows that this analogue may adopt the anti conformation on reaction with the enzyme. 5. The active species in the SnCl2-catalysed monomethylation of the 2'(3') cishydroxyls of ribonucleosides by diazomethane was shown to be an organo-tin product of the reaction of SnC2 with diazomethane. This product, not identified, contained no nitrogen or chlorine. 6. A simple column chromatographic procedure is described for the desalting of heterocyclic bases and their nucleosides with pK values for ring protonation down to about 0.
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D003978:Diazomethane; D005573:Formycins / Q000032:analysis / Q000138:chemical synthesis*; D008722:Methods; D008745:Methylation; D011720:Pyrazoles; D012266:Ribose; D014001:Tin
D000903:Antibiotics, Antineoplastic; D005573:Formycins; D011720:Pyrazoles; D003978:Diazomethane; D012266:Ribose; D014001:Tin