- Chemical-enzymatic synthesis of 3'-amino-2',3'-dideoxy-β-D- ribofuranosides of natural heterocyclic bases and their 5'-monophosphates
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Treatment of O2,3'-anhydro-5'-O-trityl derivatives of thymidine (1) and 2'-deoxyuridine (2) with lithium azide in dimethylformamide at 150 °C resulted in the formation of the corresponding isomeric 3'-azido-2',3'- dideoxy-5'-O-trityl-β-D-ribofuranosyl N1- (the major products) and N3- nucleosides 3/4 and 5/6). 3'-Amino-2',3'-dideoxy-β-D-ribofuranosides of thymidine [Thd(3'NH2)], uridine [dUrd(3'NH2)], and cytidine [dCyd(3'NH2)] were synthesized from the corresponding 3'-azido derivatives. The Thd(3'NH2) and dUrd(3'NH2) were used as donors of carbohydrate moiety in the reaction of enzymatic transglycosylation of adenine and guanine to afford dAdo(3'NH2) and dGuo(3'NH2). The substrate activity of dN(3'NH2) vs. nucleoside phosphotransferase of the whole cells of Erwinia herbicola was studied.
- Zaitseva,Kvasyuk,Vaaks,Barai,Bokut,Zinchenko,Mikhailopulo
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p. 819 - 834
(2007/10/02)
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- A facile procedure for the reduction of azido nucleosides to amines using polymer bound triphenylphosphine
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A very convenient reduction of azido nucleosides to amines under mild conditions using polystyryl diphenylphosphine resin is described. The method requires only a filtration and evaporation process for product isolation.
- Holletz,Cech
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p. 789 - 791
(2007/10/02)
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- Antineoplastic Activity of 3'-(Chloroethyl)nitrosourea Analogues of 2'-Deoxyuridine and 2'-Deoxy-5-fluorouridine
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The (chloroethyl)nitrosourea analogues of 2'-deoxyuridine and 2'-deoxy-5-fluorouridine, 3'--2',3'-dideoxyuridine (3'-CdUNU, 7) and 3'--2',3'-dideoxy-5-fluorouridine (3'-CFdUNU, 8), have been synthesized by treatment of the corresponding 3'-amino nucleosides with chloroethyl isocyanate, followed by nitrosation of the resulting ureas.Nucleoside nitrosoureas 7 and 8 exhibited marked anticancer activity against L1210 leukemia in tumor-bearing mice.At an optimum dosage level of 40 mg/kg, 7 and 8 produced 90percent and 60percent "cures" (>60-day survivors), respectively.The structure-activity relationships are discussed.
- Lin, Tai-Shun,Brubaker, William F.,Wang, Zi-Hou,Park, Susanna,Prusoff, William H.
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p. 862 - 865
(2007/10/02)
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- Synthesis and biological activity of 3'-azido- and 3'-amino substituted nucleoside analogs
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The product distribution obtained in the reaction of 1-(5-0-trityl-0-mesyl-2-deoxy-β-D-erythro-pentofuranosyl)-2,4-(1H, 3H)-pyrimidinedione with lithium azide in N, N'-dimethylformamide at 100°C depends on the nature of the substituent in 5. The results may be explained by a difference in the acidity of the pyrimidinedione. The reaction of the more acidic nucleosides (X = I, F) appears to proceed preferentially through the 2,3'-anhydro intermediate, whereas for the less acidic products (X = H, CH3) direct nucleophilic displacement by the azide ion predominates. The different 3'-azidfo derivatives were reduced to 3'-amino compounds. All 3'-azido- and 3'-aminopyrimidine nucleosides were tested against herpes simplex virus, vaccinia and vesicular stomatitis virus and on murine L1210 cell growth. None of the substances exhibited significant activity.
- Colla,Herdewijn,De Clercq,et al.
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p. 295 - 301
(2007/10/02)
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- Synthesis and antineoplastic activity of 3'-azido and 3'-amino analogues of pyrimidine deoxyribonucleoside
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Several new 3'-azido and 3'-amino nucleosides (8, 9, 12, and 13) have been synthesized and their biological activities evaluated. Among them, 3'-amino-2',3'-dideoxycytidine (13) was found to exhibit potent cytotoxic activity against both L1210 and S-180 cells in vitro with an ID50 of 0.7 and 4.0 μM, respectively. Furthermore, 13 has also shown antitumor activity against L1210 tumor bearing mice with a T/C x 100 value of 283.
- Lin,Mancini
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p. 544 - 548
(2007/10/02)
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- 3'-Amino-2',3'-dideoxyribonucleosides of some pyrimidines: Synthesis and biological activities
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3'-Amino-2',3'-dideoxyribonucleosides of thymine, uracil, and 5-iodouracil (1-3) were synthesized from the corresponding 2'-deoxyribonucleosides via the threo-3'-chloro and the erythro-3'-azido derivatives. Corresponding aminonucleosides of 5-bromouracil, 5-chlorouracil, and 5-fluorouracil (4-6) were synthesized enzymatically with 3'-amino-2',3'-dideoxythymidine as the aminopentosyl donor and thymidine phosphorylase (EC 2.4.2.4) as the catalyst. 3'-Amino-2',3'-dideoxycytidine (7) was synthesized by amination of the 3'-azido precursor of 3'-amino-2',3'-dideoxyuridine. The biological activity of 3'-amino-2',3'-dideoxy-5-fluorouridine (6) was notable among this group of aminonucleosides. It had an ED50 of 10 μM against adenovirus and was not appreciably cytotoxic to mammalian cells in culture. It also had activity against some Gram-positive bacteria but not against a variety of Gram-negative bacteria. The other aminonucleosides (1-5 and 7) lacked or exhibited weak antiviral and antibacterial activities. The only compounds in this group that were appreciably toxic to mammalian cells in culture were the thymidine and deoxycytidine analogues (1 and 7).
- Krenitsky,Freeman,Shaver,Beacham III,Hurlbert,Cohn,Elwell,Selway
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p. 891 - 895
(2007/10/02)
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