54522-22-4Relevant academic research and scientific papers
6-Methylpurine derived sugar modified nucleosides: Synthesis and evaluation of their substrate activity with purine nucleoside phosphorylases
Hassan, Abdalla E.A.,Abou-Elkhair, Reham A.I.,Parker, William B.,Allan, Paula W.,Secrist, John A.
, p. 9 - 16 (2016/01/09)
6-Methylpurine (MeP) is cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli PNP. The prototype MeP releasing prodrug, 9-(β-d-ribofuranosyl)-6-methylpurine, MeP-dR has demonstrated good activity against tumors expressing E. coli PNP, but its antitumor activity is limited due to toxicity resulting from the generation of MeP from gut bacteria. Therefore, we have embarked on a medicinal chemistry program to identify non-toxic MeP prodrugs that could be used in conjunction with E. coli PNP. In this work, we report on the synthesis of 9-(6-deoxy-β-d-allofuranosyl)-6-methylpurine (3) and 9-(6-deoxy-5-C-methyl-β-d-ribo-hexofuranosyl)-6-methylpurine (4), and the evaluation of their substrate activity with several phosphorylases. The glycosyl donors; 1,2-di-O-acetyl-3,5-di-O-benzyl-α-d-allofuranose (10) and 1-O-acetyl-3-O-benzyl-2,5-di-O-benzoyl-6-deoxy-5-C-methyl-β-d-ribohexofuran-ose (15) were prepared from 1,2:5,6-di-O-isopropylidine-α-d-glucofuranose in 9 and 11 steps, respectively. Coupling of 10 and 15 with silylated 6-methylpurine under Vorbrüggen glycosylation conditions followed conventional deprotection of the hydroxyl groups furnished 5'-C-methylated-6-methylpurine nucleosides 3 and 4, respectively. Unlike 9-(6-deoxy-α-l-talo-furanosyl)-6-methylpurine, which showed good substrate activity with E. coli PNP mutant (M64V), the β-d-allo-furanosyl derivative 3 and the 5'-di-C-methyl derivative 4 were poor substrates for all tested glycosidic bond cleavage enzymes.
C1-symmetric diphosphite ligands derived from carbohydrates: Influence of structural modifications on the rhodium-catalyzed asymmetric hydroformylation of styrene
Gual, Aitor,Godard, Cyril,Claver, Carmen,Castillon, Sergio
experimental part, p. 1191 - 1201 (2009/07/11)
New 3,5-diphosphite-substituted xylofuranoside (1b, 25a,b, and 26a,b) and glucofuranoside (3a, 7a, 8a,b) ligands with C1 symmetry have been prepared and used in the Rh-catalyzed asymmetric hydroformylation of styrene. The main structural features of these ligands are a) the presence of a 6-O-isopropyl group in ligands with a gluco configuration, b) the absence of 1,2-O-isopropylidene, a common group in many ligands with a furanoside skeleton, c) the presence of an alkyl chain bound to the 2-OH, and d) modification of the diol in the phosphite moiety. Modification of the carbohydrate backbone and diphosphite bridge affects the activity and selectivity of the reaction. Catalytic systems with ligands 1b and 8b were not active at 40 °C, although the formation of the expected hydride species [RhH(CO)2(1b)] was demonstrated by NMR spectroscopy. The highest enantioselectivity (83%) was obtained with the catalytic system Rh/8a. The complex [RhH(CO)2(8a)] was characterized by NMR spectroscopy using high-pressure techniques and was shown to exist in solution as two isomers in equilibrium; the two isomers adopt an equatorial-equatorial (eq-eq) configuration. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.
