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Ara-uridine

Conventional reversed phase HPLC is unable to separate ara-cyti-dine, ara-uridine, ribo-cytidine and ribo-uridine whereas a dual column procedure utilising an Ultrasphere ODS column in series with a Partisil PXS 10/25 SCX column gave excellent separation of these compounds (Sinkule and Evans, 1983). The accuracy of the method allowed comparative pharmacokinetic and pharmacodynamic studies to be carried out. [Pg.158]

Compound 25 (Fig. 18.9), a prodrug of 9-P-D-arabinofuranosyl guanine (26), was developed for the potential treatment of leukemia. Compound 24 is poorly soluble in water and its synthesis by conventional techniques is difficult. An enzymatic demethoxylation process was developed using adenosine deaminase (Mahmoudian et al., 1999, 2001). Compound 25 was enzymatically prepared from 6-methoxyguanine (27) and ara-uracil (28) using uridine phosphorylase and purine nucleotide phosphorylase. Each protein was cloned and overexpressed in independent Escherichia coli strains. Fermentation conditions were optimized for production of both enzymes and a co-immobilized enzyme preparation was used in the biotransformation process at 200 g/L substrate input. Enzyme was recovered at the end of the reaction by filtration and reused in several cycles. A more water soluble 5 -acetate ester of compound 26 was subsequently prepared by an enzymatic acylation process using immobilized Candida antarctica lipase in 1,4-dioxane (100 g/L substrate) with vinyl acetate as the acyl donor (Krenitsky et al., 1992). [Pg.330]

The introduction of an azido substituent on the C-2 position of cytosine arabinoside (ara-C) (149) or adenosine arabinoside (ara-A) (154) has been found to confer favourable properties to these antimetabolites. Ara-C, one of the most effective drugs for the treatment of human acute myeloblastic leukaemia [176], is subject to rapid metabolic deamination, by deoxycytid-ine deaminase, to the inactive uridine derivative ara-U (152) Scheme 3.5), and the drug has a half-life of approximately 12 minutes in man [177]. Efforts to circumvent this problem by modifying the 2 -arah/ o-position led... [Pg.176]

By modifications of known procedures, the following compounds have been prepared l-P-D-arabinofuranosylth3miine,2 -deoxy-5-(trifluoromethyl)-uridine and its a-anomer, a- and p-5-trifluoromethyl-6-aza-2 -deoxyuri-dlnes,l-p-D-arabinofuranosyl-5-fluorouracil,5-fluoro-2 deoxycyti-dine,24 3 -deoxynucleosides of pyrimidines, pyrimidine and purine nucleosides of D-glucuronlc acid, 9-D-mannofuranosyladenlne, 3-P-D-ara-... [Pg.305]

The syntheses of carbocyclic analogs of phosphononucleosides (29) and (30a-c) have been reported. Phosphonic acid (29) was obtained by introduction of the benzoylated thymine on the 2(4-hydroxycyclopent-2-enyl)ethyl phosphonic acid diisopropyl ester under Mitsunobu conditions while (30a-c) were prepared by building-up the base around a phosphono-cyclopentylamine moi-ety. The vinylphosphonate derivatives of uridine, cytidine and cytosine ara-binoside (31a-c) have been prepared by Wittig condensation of [(diethoxyphos-phinyl)methylidene]triphenylphosphorane with the appropriately protected 5-aldehydic nucleoside derivatives. Dihydroxylation of the novel vinyl phosphon-ates offered the dihydroxylated phosphonate derivatives (32a-c). Each of these novel compounds was evaluated as substrates for the enzyme nucleotide monophosphate kinase, and their toxicity to K562 cells. All analogues were found to be poorly phosphorylated by the kinase and exhibited poor in vivo toxicity. ... [Pg.169]

Liu reported the first chemical synthesis of uridine 5 -diphospho-P-L-ara-binofuranose (117), a possible donor of L-arabinofuranose residue. Compound (117) underwent interconversion with UDP-p-L-arabinopyranose, the likely precursor of L-arabinofuranose in vivo, when incubated with UDP-galactopyranose mutase. This result provided insights into the biogenesis of L-arabinofuranose in plants. ... [Pg.193]

Chiral 2, 3 -. eco-2 -deoxy nucleosides were conveniently prepared from uridine 75 (R = OH) and its analogue l-(a-D-ara/)/rtofuranosyl) uracil. The 3, 5 -dihydroxy groups in 2, 3 -5m )-uridine 77 or 82, obtained from 76 or... [Pg.407]

We decided to apply a microbial enzyme that catalyzes the trans-arabinosylation reaction, as shown in Fig. 1. The enzyme substrate uracil arabinoside (ara-U) can be prepared from uridine through reaction with ethylene carbonate followed by the hydrolysis of cydo-uridine (cyclo-U) by add. )... [Pg.122]

In Fig. 9, uridine was selected as the starting raw material for the synthesis of pentose-modified purine nucleosides such as ara-A, 2AA and DDA. [Pg.128]

Nucleoside X (1) has been isolated from the variable loop of E. coli tRNA the analogues (2) and (3) were prepared from uridine. The modified mammalian tRNA nucleoside (4) has been characterized by mass spectrometry. 2-O-Methyl-uridine has been isolated from human urine, and a new species of Streptomyces herbaceus has been shown to produce Ara-A(9-j3-D-arabinosyladenine). ... [Pg.173]

Vinylphosphonates of cytosine, uracil and ara-C have been prepared by Wittig reactions, and intermediates in these syntheses were hydroxylated using AD-mix-a to give the product 196 and the related derivatives of uridine and cytosine, Geminal hydroxyphosphonates 197 (R = Me or H, and with all four nucleobases) have been prepared by addition of dimethyl phosphite or tris-Tms phosphite to 5 -aldehydes. Similar products were obtained from 2, 3 -0-iso-propylidene ribonucleosides, except in the case of adenosine. NMR studies indicated that the major diastereoisomer formed in each case had 5 -R-stereochemistry, and in some cases this was produced in up to 90% d.e. ... [Pg.274]

Pyrimidines - The leukocytes of patients responding to l- -D-arabino-furanosylcytosine (ara-C) exhibited reduced DNA and elevated RNA and protein contents, whereas the normal bone marrow cells of these patients exhibited increased DNA, RNA, and protein contents. Despite extensive intracellular conversion of ara-C to nucleotides, only limited incorporation of the compounds into nucleic acids occurred. 2-Deoxy-cytidine reverses the effects of ara-C by inhibiting its phosphorylation, an anabolic step that must occur before it can inhibit DNA polymerase and, consequently, cell proliferation. Uridine exerts a sparing action on ara-C, and the effective level of this drug can be prolonged by coadministration of tetrahydrouridine, a potent inhibitor of deoxycytidyl-ate aminohydrolase. ... [Pg.156]

Rlbofuranosyl nucleosides trltiated at the 5 -position have been prepared by borotrltlide reduction of 5 -aldehydes. and also by using [S - HJ- uridine as ribosyl donor in an enzymic transribosylation using immobilised nucleoside phosphorylase.24 Routes have been developed for the synthesis of adenosine labelled with 0 at either 0-2 or 0-3, and for the corresponding isotopomers of ara-A in each case label was Introduced from [i 0]-cesium propionate by reaction with an epoxide or a triflate.25... [Pg.206]

When 2 -deojreact with acetyl hypofluorite. adduct (10) was formed together with the alternative cis-diastereomer. Treatment of (10) with ferric chloride in dry acetonitrile gave the Q, 5 -cyclonucleoside (11), and the other diastereomer behaved similarly. Similar reactions occur with uridine and ara-U. but in the latter case some 0 , 2 -cyclonudeoside formation is also found.37... [Pg.207]

Carbocyclic analogues of 2 -azido- and 2 -amino-2 -deoxyuridine (58) have been made from the known carbocyclic uridine via the 2,2 -cyclonucleoside.ii i The carbocyclic analogue of 2 -deoxy-2 -fluoro-ara-G (59)... [Pg.216]

The synthesis of 1-g-D-arabinofuranosylcytosine and some derivatives has been reviewed. Syntheses reported for other ara-nucleosides include spongo-uridine, ara-tubercidin, and the a- and -anomers of ara-7-deazaguanosine prepared by phase-transfer catalysis. Conventional methods have been used to prepare D-glucofuranose derivatives of uracil and thymine,a g-D-glucopyranosyl derivative of nicotine, and 9-(3,4-anhydro-6-deoxy-a-L-talopyranosyl)-6-benzoyl-adenine from L-rhamnose. ... [Pg.206]


See other pages where Ara-uridine is mentioned: [Pg.53]    [Pg.208]    [Pg.127]    [Pg.208]    [Pg.217]    [Pg.191]    [Pg.210]    [Pg.53]    [Pg.208]    [Pg.127]    [Pg.208]    [Pg.217]    [Pg.191]    [Pg.210]    [Pg.134]    [Pg.264]    [Pg.254]    [Pg.528]    [Pg.31]    [Pg.370]    [Pg.160]    [Pg.236]    [Pg.160]    [Pg.401]    [Pg.122]    [Pg.1141]    [Pg.121]    [Pg.169]    [Pg.52]    [Pg.134]    [Pg.239]    [Pg.261]    [Pg.263]    [Pg.1164]    [Pg.122]    [Pg.125]    [Pg.179]    [Pg.289]    [Pg.290]    [Pg.147]   
See also in sourсe #XX -- [ Pg.158 ]




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