Nucleosides. CXXXV. Synthesis of some 9-(2-deoxy-2-fluoro-B-D-arabinofuranosyl)-9H-purines and their biological activities Journal Article
| Authors: | Chu, C. K.; Matulic-Adamic, J.; Huang, J. T.; Chou, T. C.; Burchenal, J. H.; Fox, J. J.; Watanabe, K. A. |
| Article Title: | Nucleosides. CXXXV. Synthesis of some 9-(2-deoxy-2-fluoro-B-D-arabinofuranosyl)-9H-purines and their biological activities |
| Abstract: | Seven purine nucleosides containing the 2'-deoxy-2'-fluoro-/?-D-arabinofuranosyl moiety were synthesized and tested for their antitumor activity. Direct condensation of 3-0-acetyl-5-0-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (1) with A^-benzoyladenine in CH2C12followed by saponification of the product afforded the adenine nucleoside (I, 2'-F-ara-A). Deamination of I with NaN02in HOAc gave the hypoxanthine analogue (II, 2'-F-ara-H). The 6-thiopurine nucleoside (III, 2'-F-ara-6MP) was prepared by condensation of 1 with 6-chloropurine by the mercury procedure followed by thiourea treatment and saponification of the product. Methylation of III gave the 6-SCH3 analogue (IV). Raney Ni desulfurization of III afforded the unsubstituted purine nucleoside (V, 2'-F-ara-P). Condensation of 1 with 2-acetamido-6-chloropurine by the silyl procedure afforded the protected 2-acetamido-6-chloropurine nucleoside which served as the precursor for both the guanine and 6-thioguanine nucleosides (VI, 2'-F-ara-G and VII, 2'-F-ara-TG, respectively). Thus, alkaline hydrolysis of the precursor gave VI. Thiourea treatment prior to alkaline hydrolysis gave VII. The new nucleoside, 2'-F-ara-G (VI) is found to be selectively toxic to human T-cell leukemia CCRF-CEM. © 1989, The Pharmaceutical Society of Japan. All rights reserved. |
| Keywords: | leukemia; unclassified drug; human cell; nonhuman; antineoplastic agents; animal cell; mouse; animal; mice; biological model; cytotoxicity; drug synthesis; chemistry; cell culture; nuclear magnetic resonance; protozoon; antiviral agents; arabinonucleosides; purine nucleosides; leishmania; human; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; 2' deoxy 2' fluorovidarabine; 2' fluoro 2' deoxyhypoxanthine arabinoside; 2-fluoro-arabinosylguanine antitumor activity; nucleoside purine nucleoside 2',-fluoro-arabinosylpurine; 2' deoxy 2' fluoroguanine arabinoside; 2' deoxy 2' fluorothioguanine arabinoside; 2' fluoro 2' deoxypurine arabinoside; cell strain ccrf cem |
| Journal Title: | Chemical and Pharmaceutical Bulletin |
| Volume: | 37 |
| Issue: | 2 |
| ISSN: | 0009-2363 |
| Publisher: | Pharmaceutical Society of Japan |
| Date Published: | 1989-02-01 |
| Start Page: | 336 |
| End Page: | 339 |
| Language: | English |
| DOI: | 10.1248/cpb.37.336 |
| PUBMED: | 2743479 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
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