Seley K L, Schneller S W, De Clercq E, Rattendi D, Lane S, Bacchi C J, Korba B
Department of Chemistry, Auburn University, AL 36849-5312, USA.
Bioorg Med Chem. 1998 Jun;6(6):797-801. doi: 10.1016/s0968-0896(98)00036-4.
(+)-5'-Noraristeromycin (1) has shown significant antiviral activity while its 7-deaza analogue 2 is an antitrypanosomal candidate. To determine the relevance of the 4'-hydroxyl hydrogen in these activities, a derivative of 1 (that is, 3) where the C-4' hydroxyl hydrogen has been replaced by a methyl group has been prepared beginning with palladium (0) mediated coupling of the sodium salt of N6-benzoyladenine (9) and (1S,4R)-4-methoxy-2-cyclopenten-1-yl acetate (5). The synthesis of compound 5 is described from (1S,4R)-1-[(tert-butyldimethylsilyl)oxy]-4-hydroxycyclopent-2-ene (6) in three steps. Analogous preparations of the 7-deaza and 8-aza-7-deaza derivatives of 3 related to 2 (that is, 4 and 12) are also reported. The new derivatives (3, 4, and 12) failed to show improved antiviral activity. Compound 12 was the only derivative with some anti-trypanosomal activity, giving 40% inhibition of growth at 100 microM against bloodstream forms of a Typanosoma brucei brucei isolate in a standard in vitro screen. This study indicated that the C-4'-hydroxyl hydrogen plays a role in the medicinal properties of 1 and 2.
(+)-5'-去甲阿霉素（1）已显示出显著的抗病毒活性，而其7-脱氮类似物2是一种抗锥虫候选物。为了确定4'-羟基氢在这些活性中的相关性，已从N6-苯甲酰腺嘌呤（9）的钠盐与（1S,4R）-4-甲氧基-2-环戊烯-1-基乙酸酯（5）的钯（0）介导的偶联开始，制备了1的一种衍生物（即3），其中C-4'羟基氢已被甲基取代。化合物5的合成是从（1S,4R）-1-[(叔丁基二甲基甲硅烷基)氧基]-4-羟基环戊-2-烯（6）分三步描述的。还报道了与2相关的3的7-脱氮和8-氮杂-7-脱氮衍生物（即4和12）的类似制备方法。新衍生物（3、4和12）未显示出改善的抗病毒活性。化合物12是唯一具有一定抗锥虫活性的衍生物，在标准体外筛选中，对布氏锥虫布鲁斯亚种分离株的血流形式在100 microM时生长抑制率为40%。这项研究表明，C-4'-羟基氢在1和2的药用特性中起作用。
