Chu C K, Matulic-Adamic J, Huang J T, Chou T C, Burchenal J H, Fox J J, Watanabe K A
Chem Pharm Bull (Tokyo). 1989 Feb;37(2):336-9. doi: 10.1248/cpb.37.336.
Seven purine nucleosides containing the 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl moiety were synthesized and tested for their antitumor activity. Direct condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide (1) with N6-benzoyladenine in CH2Cl2 followed by saponification of the product afforded the adenine nucleoside (I, 2'-F-ara-A). Deamination of I with NaNO2 in 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.
合成了七种含有2'-脱氧-2'-氟-β-D-阿拉伯呋喃糖基部分的嘌呤核苷，并对其抗肿瘤活性进行了测试。3-O-乙酰基-5-O-苯甲酰基-2-脱氧-2-氟-D-阿拉伯呋喃糖基溴（1）与N6-苯甲酰腺嘌呤在二氯甲烷中直接缩合，然后将产物皂化，得到腺嘌呤核苷（I，2'-F-ara-A）。I在醋酸中用亚硝酸钠脱氨得到次黄嘌呤类似物（II，2'-F-ara-H）。6-硫代嘌呤核苷（III，2'-F-ara-6MP）通过汞法将1与6-氯嘌呤缩合，然后进行硫脲处理并将产物皂化制备。III甲基化得到6-SCH3类似物（IV）。III经雷尼镍脱硫得到未取代的嘌呤核苷（V，2'-F-ara-P）。1与2-乙酰氨基-6-氯嘌呤通过硅烷化方法缩合得到受保护的2-乙酰氨基-6-氯嘌呤核苷，它是鸟嘌呤和6-硫代鸟嘌呤核苷（分别为VI，2'-F-ara-G和VII，2'-F-ara-TG）的前体。因此，前体经碱性水解得到VI。在碱性水解之前进行硫脲处理得到VII。发现新核苷2'-F-ara-G（VI）对人T细胞白血病CCRF-CEM具有选择性毒性。
