RESUMEN
Six cyclobutanetetraone poly(arylhydrazones) have been treated with acids and bases, and the structures of the resulting anions and cations studied by UV-Vis absorption and NMR spectroscopy. In acid media, all the hydrazones studied formed cations, which exhibited bathochromic shifts due to the extension of their resonance systems. However, in bases, only some (those which could enolize) formed anions that exhibited hypsochromic shifts; the others were unaltered.
Asunto(s)
Aniones/química , Cationes/química , Hidrazonas/química , Polímeros/química , Espectrometría de Masas , Resonancia Magnética Nuclear Biomolecular , Espectrofotometría UltravioletaRESUMEN
Reaction of 6-deoxy-2,3,5-tris-O-(p-nitrobenzoyl)-L-talofuranosyl bromide (1) with the trimethylsilyl derivative of hypoxanthine, followed by removal of blocking groups, afforded 9- (6) and 7-(6'-deoxy-alpha-L-talofuranosyl)hypoxanthine (7). A study of the published optical rotations and circular dichroic (CD) spectra of pentofuranosylpurines and of (6'-deoxy-beta-D-allo- and -alpha-L-talofuranosyl)purines prepared here suggests that the sign of rotation and the sign of the longer wavelength Cotton effect is determined solely by the configuration of C-1' and its position of attachment to the purine ring. For C-1' R nucleosides, the sign is negative for N-9-linked purine nucleosides and positive for the N-7-linked isomers, and vice versa for C-1'S purine nucleosides. Reaction of 1 with the trimethylsilyl derivative of 6-chloropurine afforded 4, which upon treatment with thiourea and deblocking yielded 9-(6'-deoxy-alpha-L-talofuranosyl)-6-thiopurine (8). Unlike the previously prepared 7-(6'-deoxy-beta-D-allofuranosyl) hypoxanthine which strongly inhibited purine nucleoside phosphorylase, compounds 6-8 did not inhibit this enzyme. Compound 8 significantly inhibited the growth of L1210 tumor cells in vitro and in vivo.
Asunto(s)
Antineoplásicos/síntesis química , Inosina/análogos & derivados , Leucemia L1210/tratamiento farmacológico , Nucleósidos de Purina/síntesis química , Tionucleósidos/síntesis química , Animales , Evaluación Preclínica de Medicamentos , Indicadores y Reactivos , Inosina/síntesis química , Inosina/uso terapéutico , Espectroscopía de Resonancia Magnética , Mercaptopurina/uso terapéutico , Ratones , Rotación Óptica , Nucleósidos de Purina/uso terapéutico , Espectrofotometría , Relación Estructura-Actividad , Tionucleósidos/uso terapéuticoRESUMEN
Hypoxanthine, guanine, and 6-thiopurine nucleosides of 6-deoxy-D-allofuranose have been prepared as potential antitumor agents. Thus, reaction of 6-deoxy-beta-D-allofuranosyl bromide (1) with the trimethylsilyl derivatives of hypoxanthine and guanine afforded mixtures of the 9- and the 7-substituted bases, which were separated and deblocked with ammonia to give 9-(6'-deoxy-beta-D-allofuranosyl)hypoxanthine (6), 7-(6'-deoxy-beta-D-allofuranosyl)hypoxanthine (7), 9-(6'-deoxy-beta-D-allofuranosyl)guanine (8), and 7-(6'-deoxy-beta-D-allofuranosyl)guanine (9). The two nucleosides with the purine joined at the N-9 position, namely, 6 and 8, are easily distinguished from the other two nucleosides (7 and 9), having N-7 junctions, by their NMR spectra. Reaction of 1 with the trimethylsilyl derivative of 6-chloropurine afforded 10, which upon treatment with thiourea and deblocking gave 9-(6'-deoxy-beta-D-allofuranosyl)-6-thiopurine (12). The hypoxanthine and guanine nucleosides showed no inhibition of mouse leukemia L1210 when tested in vivo, but the thiopurine nucleoside 12 showed strong inhibition of growth of L1210 both in vivo and in vitro. Compound 7 strongly inhibited purine nucleoside phosphorylase (KI = 8.8 X 10(-5) M), while compounds 8, 9, 6, and 12 were inactive.
Asunto(s)
Desoxiguanosina/síntesis química , Inosina/análogos & derivados , Nucleósidos/síntesis química , Nucleósidos de Purina/síntesis química , Tionucleósidos/síntesis química , Animales , Desoxiguanosina/farmacología , Desoxiguanosina/uso terapéutico , Guanina , Hipoxantina , Hipoxantinas , Indicadores y Reactivos , Inosina/síntesis química , Inosina/uso terapéutico , Leucemia L1210/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Ratones , Nucleósidos de Purina/farmacología , Espectrofotometría Ultravioleta , Relación Estructura-Actividad , Tionucleósidos/farmacologíaRESUMEN
Treatment of di-O-acetyl-2-deoxy-L-fucopyranosyl bromide with carminomycinone and epsilon-pyrromycinone in the presence of mercuric bromide and mercuric cyanide afforded 3',4'-diO-acetyl-2'-deoxy-L-fucopyranosylcarminomycinone and -epsilon-pyrromycinone. Similarly, when di-O-acetyl-2-deoxy-D-erythrho-pentopyranosyl chloride was treated with daunomycinone, carminomycinone and epsilon-pyrromycinone, the di-O-acetyl derivatives of the anthracyclinone glycosides were obtained. Deacetylation of the previous acetates with sodium methoxide afforded 2'-deoxy-L-fucopyranosylcarminomycinone and -epsilon-pyrromycinone, as well as 2'-deoxy-D-erythro-pentopyranosyldaunomycinone, -carminomycinone, and -epsilon-pyrromycinone. 2'-Deoxy-L-fucopyranosylcarminomycinone was found to be more active than carminomycin at higher dosages on L1210.
Asunto(s)
Antraciclinas , Antibióticos Antineoplásicos/síntesis química , Naftacenos/síntesis química , Animales , Bacterias/efectos de los fármacos , Carubicina/análogos & derivados , Carubicina/síntesis química , Carubicina/farmacología , Fenómenos Químicos , Química , Ratones , Naftacenos/farmacologíaRESUMEN
Twenty-six episilon-rhodomycinone glycosides have been synthesized. These include the episilon-rhodomycinone glycosides of 2-deoxy-L-fucose, 2-deoxy-L-rhamnose, and 2-deoxy-D-ribose as well as their 2-hydroxyl derivatives. NMR spectroscopy showed that all the glycosides prepared had the saccharide residues linked to position 10 of episilon-rhodomycinone and helped establish the anomeric purity and configuration of several glycosides. Preliminary screening results show that 2-deoxy-di-O-acetyl-D-ribopyranosyl-episilon-rhodomycinone has an activity T/C of 125 on P388 tumors.
Asunto(s)
Antraquinonas/síntesis química , Glicósidos/síntesis química , Animales , Antraciclinas , Antraquinonas/farmacología , Antibacterianos/síntesis química , Antineoplásicos/síntesis química , Antineoplásicos/uso terapéutico , Bacillus subtilis/efectos de los fármacos , Fenómenos Químicos , Química , Glicósidos/farmacología , Glicósidos/uso terapéutico , Leucemia Experimental/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Métodos , RatonesRESUMEN
3-Deoxy-2,5-di-O-p-nitrobenzoyl-alpha-D-threo-entofuranosyl bromide (1) reacted with mercuric cyanide to give 2,5-anhydro-4-deoxy-D-lyxo-hexononitrile (2) which upon acid hydrolysis of the CN group gave acid 3. Saponification of the protecting groups gave 2,5-anhydro-4-deoxy-D-lyxo-hexonic acid (4) which reacted with 4,5,6-triaminopyrimidine forming an amide (5) that was pyrolized to give 8-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine (6). Reaction of bromide 1 with 6-(benzamido) chloromercuriopurine followed by saponification yielded 9-(3'-deoxy-alpha-D-threo-pentofuranosyl)adenine(8). 8-(beta-D-Ribofuranosyl)adenine, 8-(beta-D-arabinofuranosyl)adenine, and 8-(3'-deoxy-beta-D-erythro-pentofuranosyl)adenine, as well as compound 6, showed no antimalarial activity.