ABSTRACT
N4-Acetyl-1-(2, 3-di-O-acetyl-4-thio-beta-D-arabinofuranosyl) cytosine (2) was synthesized in three steps from 1-(4-thio-beta-D-arabinofuranosyl) cytosine (1). The reaction of this partially blocked 4'-thio-ara-C derivative 2 with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one gave the 5-phosphitylate derivative 3, which on reaction with pyrophosphate gave the 5'-nucleosidylcyclotriphosphite 4. Product 4 was then oxidized with iodine/pyridine/water and deblocked with concentrated ammonium hydroxide to provide the desired 4'-thio-ara-C-5'-triphosphate 5. This triphosphate 5 was converted to 4'-thio-ara-C -5'-monophosphate 6 by treatment with snake venom phosphodiesterase I. The details of the synthesis, purification, and characterization of both nucleotides are described.
Subject(s)
Arabinofuranosylcytosine Triphosphate/chemical synthesis , Arabinonucleotides/chemistry , Cytidine Monophosphate/analogs & derivatives , Ammonium Hydroxide , Arabinofuranosylcytosine Triphosphate/chemistry , Arabinonucleotides/chemical synthesis , Chemistry, Pharmaceutical , Chromatography, Ion Exchange , Cytidine Triphosphate/analogs & derivatives , Cytidine Triphosphate/chemical synthesis , Cytidine Triphosphate/chemistry , Diphosphates/chemistry , Drug Design , Hydroxides/chemistry , Models, Chemical , Molecular Structure , Phosphodiesterase I/chemistry , Polyphosphates/chemistry , Water/chemistryABSTRACT
The coupling of 4-aminopyrazolo [3, 4-d]pyrimidine with the appropriate thio sugar gave a 3:1 ratio of alpha,beta blocked 4-amino-1-(2-deoxy-4-thio-D-erythropentofuranosyl)-1H pyrazolo[3,4-d]pyrimidine nucleosides. The mixture was deblocked, both the anomers were separated, and the beta-anomer was readily deaminated by adenosine deaminase. The nucleosides have been characterized, and their anomeric configurations have been determined by proton NMR. All three nucleosides were evaluated against a panel of human tumor cell lines for cytotoxicity in vitro. The details of a convenient and high yielding synthesis of these nucleosides are described.
Subject(s)
Adenosine/chemistry , Molecular Biology/methods , Nucleosides/chemistry , Nucleosides/chemical synthesis , Purine Nucleosides/chemical synthesis , Pyrimidines/chemistry , Cell Line, Tumor , Drug Design , Drug Screening Assays, Antitumor/methods , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy/methods , Models, Chemical , Protons , Purine Nucleosides/chemistry , Pyrimidine Nucleosides/chemistryABSTRACT
Abstract Traditional methods to assess changes in dietary intake, for example food frequency questionnaires or 24-hour dietary recalls, are often not practical: they are lengthy, expensive, and unsuitable for telephone administration. This article describes the development and evaluation of an approach to the rapid assessment of the dietary intake of nutrients of most interest in health promotion research; total fat, saturated fat, dietary fiber, and percent of calories from fat. In this validation study on 97 women, short dietary questionnaires were compared to two criterion measures of usual dietary intake, a food frequency questionnaire and the mean of two four-day diet records. Correlations between self-administered short questionnaires and four-day diet records were 0.52, 0.53, 0.61, and 0.40 for total fat, percent of calories from fat, saturated fat, and dietary fiber, respectively. These correlations are similar to those observed between food frequency questionnaires and four-day diet records, which suggests that this approach to developing and administering short dietary questionnaires may be useful in situations where more expensive and time-consuming methods of dietary assessment are not practical.
