Nucleoside derivatives analysis

In summary, although novel therapies not based upon nucleoside derivatives are being put forward into clinics, combined treatments still rely upon nucleoside derivatives, thus making the type of studies summarized above still mandatory for a better understanding of interindividual differences in patient response to therapy. Actually, as previously discussed, nucleoside transporter expression is variable in human tumors, and evidence provided so far indicates a putative role of NTs in nucleoside-derived drug bioavailability and responsiveness. Prospective clinical studies focused on NTs as biomarkers of drug metabolism and action are required to better establish the role these membrane proteins might play in cancer chemotherapy. This would eventually lead to the analysis of NT expression patterns as suitable predictors of response to therapy and patient outcome. 

Evidence for the /3-d configuration of the anomeric center (C-1) of the purine nucleosides derived from the nucleic acids was obtained by Fur-berg, using x-ray crystallographic analysis, and by Todd and coworkers, whose studies of the anhydronucleosides (7 and 8) derived from... 

The application of gas-liquid chromatography td the analysis of nucleosides has been described, and the retention volumes of some nucleoside derivatives are given in Table XIII. Although the free nucleosides are not sufficiently volatile, derivatives in which the hydroxyl or amino groups had been blocked by combinations of acetylation, methylation, or iso-propylidene acetal formation could be eluted successfully. The peaks obtained were well defined and reproducible, although antisymmetrical. 

The sequence analysis of oligo(2 -deoxyribonucleotides) by mass spectrometry is mentioned in Chapter 21, which also contains a list of nucleoside derivatives whose structures have been analysed by X-ray crystallography. The interaction between Cu cations and adenosine, guanosine, cytidine, and uridine in aqueous DMSO has been discussed in Chapter 16. 

Dideoxy-adenosine, -inosine, and -cytidine have been determined in biological samples by both reversed-phase and ion-pair reversed-phase methods. An ion-pair (Bu" N ) reversed-phase analysis of purine nucleosides, bases, nucleotides, dinucleotides, and nucleoside derivatives (adenosyl-homocysteine, -succinate, and -methionine) from acid-extracted tissues was undertaken to investigate adenosine reservoirs in rats on treatment with a metabolic inhibitor which blocks adenosine transport. 

In the course of studies on azide-tetrazole equilibria, some azido derivatives 73 of this ring system have been subjected to X-ray structure elucidation <2005JST(751)65>. These derivatives proved to be mainly planar and the least planar part of these molecules were the azide moieties. In both cases (72 R= H and Me), formation of hydrates were also observed. Crystallographic analysis of the trifluoromethyl compound was described by Lange et al. <1997APH299>, and structure elucidation of the nucleoside analogue 74 was reported by Stanovnik et al. <1998JHC513>. 

In studies on new bicyclic nucleosides the derivative 57 containing a ribose moiety has been synthesized <1996TL901>. The X-ray analysis showed that the CO bond attached to the triazine ring is only slightly longer (1.23 A) than a standard carbonyl bond. 

Addition of lithiated heterocycles to aldonolactones yields carbon-linked nucleosides (56). Thus, the reaction of 2,3 5,6-di-O-isopropylidene-L-gu-lono-1,4-lactone (9b) or 2,3-O-isopropylidene-D-ribono-l,4-lactone (16a) with various lithiated heterocycles gave gulofuranosyl derivatives 53a-g or ribofuranosyl derivatives 54b,c. Gulonolactols 53a-g and ribonolactols 54b,c were acetylated with acetic anhydride in pyridine to yield their acetyl derivatives. The stereochemistry of compounds 53a-g and 54b,c was discussed in terms of the Cotton effect of circular-dichroism curves of the ring-opened alcohols formed upon reduction by sodium borohydride. The configuration at C-l of 53g was proved by means of X-ray analysis (57,58). 

The unambiguous characterization of glycosyl esters of nucleoside pyrophosphates is difficult, as no suitable crystalline derivatives are known for them, and the hygroscopic nature of their ammonium and metal salts prevents reliable interpretation of the data of elementary analysis. 

CD detection for colored derivatives might just as easily be used for structural information about the carbohydrates as well as for their analysis, but so far little attention has been given to either application. Cyclic oligomers of p-D-glucose have important supporting roles to play in analytical applications that are discussed in a later section. The union of chirality in the carbohydrate moiety of a glycoside metabolite with the unsaturation in the base in such compounds as nucleosides and nucleotides, saponins and flavones, etc., is another area that will ultimately be developed for applications of chiroptical detection methods. New and imaginative ideas are needed for the analysis of carbohydrates, and CD should be one of the favored methods. 

As far as quantitative chemical derivatization GC analysis is concerned, it is necessary to mention especially the work of Gehrke and his collaborators, who specified the fundamental concepts of quantitative GC analysis combined with the chemical derivatization of sample compounds and applied them to the accurate determination of the twenty natural protein amino acids and other non-protein amino acids as their N-TFA-n-butyl esters [5 ], the urinary excretion level of methylated nucleic acid bases as their TMS derivatives [6], TMS nucleosides [7] and other investigations. Further examples include a computer program for processing the quantitative GC data obtained for seventeen triglyceride fatty acids after their transesterification by 2 NKOH in n-butanol [8], a study of the kinetics of the transesterification reactions of dimethyl terephthalate with ethylene glycol [9] and the GC-MS determination of chlorophenols in spent bleach liquors after isolation of the chlorophenols by a multi-step extraction, purification of the final extract by HPLC and derivatization with diazoethane [10]. 

Gehrke and Patel [460] looked for optimal reaction and chromatographic conditions in the analysis of silyl derivatives of nucleosides prepared by reaction with BSTFA. They recommended performing the derivatization with a 225-fold molar excess of BSTFA at 150°C for 15 min in a closed vial and analysis on a 1 m X 4 mm ED. column packed with 4% of OV-11 on Supelcoport (100—120 mesh) with temperature programming at 5°C/ min from 140°C. 

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