Synthesis and Biological Activity of 5‐Fluorotubercidin
- 1 January 2004
- journal article
- Published by Taylor & Francis in Nucleosides, Nucleotides and Nucleic Acids
- Vol. 23 (1-2) , 161-170
- https://doi.org/10.1081/ncn-120027825
Abstract
The electrophilic fluorination of 4-chloropyrrolo[2,3-d]pyrimidine (1) was studied culminating a 59% conversion of compound 1 to 4-chloro-5-fluoropyrrolo[2,3-d]pyrimidine (2) using Selectfluor. This transformation proceeded via the 4-chloro-5,6-dihydro-5-fluoro-6-hydroxypyrrolo[2,3-d]pyrimidine (3) in a 9:1 trans:cis ratio. The trans isomer of compound 3 was studied by 1H NMR and 19F NMR, and the 5-H tautomer (4) was observed as another intermediate. A modified Vorbruggen procedure of compound 2 and tetra-O-acetylribose gave 4-chloro-5-fluoro-7-(2,3,5,-tri-O-benzoyl-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine (6) in a 65% yield. Treatment of compound 6 with ammonia (l) in dioxane gave 5-fluorotubercidin (7). No antibacterial activity was observed. An MTT assay (Promega) against Huh-7 liver cells, normal mouse spleen cells stimulated with Con A (a T-cell mitogen), and normal mouse spleen stimulated with LPS (a B-cell mitogen) showed no significant toxicity. Increased activity of 7 over tubercidin was observed against L-1210 cells and toxicity in fibroblast cells was reduced.Keywords
This publication has 22 references indexed in Scilit:
- Adenosine Kinase Inhibitors. 1. Synthesis, Enzyme Inhibition, and Antiseizure Activity of 5-Iodotubercidin AnaloguesJournal of Medicinal Chemistry, 2000
- Chemistry of Nucleosides and NucleotidesPublished by Springer Nature ,1994
- Synthesis of Tubercidin, 6-Chlorotubercidin and Related NucleosidesNucleosides, Nucleotides and Nucleic Acids, 1989
- Synthesis and antiviral activity of certain 4- and 4,5-disubstituted 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidinesJournal of Medicinal Chemistry, 1988
- Xylotubercidin against herpes simplex virus type 2 in miceAntimicrobial Agents and Chemotherapy, 1986
- Antirhinovirus activity of purine nucleoside analogsAntimicrobial Agents and Chemotherapy, 1986
- Synthesis and biological activity of certain 6-substituted and 2,6-disubstituted 2'-deoxytubercidins prepared via the stereospecific sodium salt glycosylation procedureJournal of Medicinal Chemistry, 1985
- Antiviral activity of C-5 substituted tubercidin analogsJournal of Medicinal Chemistry, 1984
- Total synthesis of certain 2-, 6-mono- and 2,6-disubstituted-tubercidin derivatives. Synthesis of tubercidin via the sodium salt glycosylation procedureNucleic Acids Research, 1984
- Activity of tubercidin-, toyocomycin-, and sangivamycin-3′,5′-cyclic phosphates and related compounds with some enzymes of adenosine-3′, 5′-cyclic phosphate metabolismBiochemical and Biophysical Research Communications, 1973