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.