Roy Atanu, Schneller Stewart W, Keith Kathy A, Hartline Caroll B, Kern Earl R
Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA.
Bioorg Med Chem. 2005 Jul 15;13(14):4443-9. doi: 10.1016/j.bmc.2005.04.044.
As a surrogate for 4'-hydroxy-5'-noraristeromycin and related carbocyclic nucleosides, an efficient, enantiodivergent synthetic route to both enantiomers of 5-(6-amino-9H-purin-9-yl)-3,3-difluorocyclopentane-1,2-diol (6 and ent-6) has been developed from a common starting material ((+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate, 10). Both compounds were assayed versus a series of viruses. The only response found was for compound 6 toward vaccinia and cowpox (EC50 of 143 and 94 microM, respectively) and human cytomegalovirus (EC50 of 6.2 microM). Both compounds were non-cytotoxic. While not as active as cidofovir toward the orthopox viruses and ganciclovir toward cytomegalovirus, compound 6 offers a new structural prototype upon which to build for uncovering new agents effective against these viral types.
作为4'-羟基-5'-去甲阿瑞司他霉素及相关碳环核苷的替代物，已从一种常见起始原料（(+)-(1R,4S)-4-羟基-2-环戊烯-1-基乙酸酯，10）开发出一条高效、对映发散的合成路线，用于制备5-(6-氨基-9H-嘌呤-9-基)-3,3-二氟环戊烷-1,2-二醇（6和对映体ent-6）的两种对映体。对这两种化合物针对一系列病毒进行了测定。唯一发现的反应是化合物6对痘苗病毒和牛痘病毒（EC50分别为143和94 microM）以及人巨细胞病毒（EC50为6.2 microM）有活性。这两种化合物均无细胞毒性。虽然化合物6对正痘病毒的活性不如西多福韦，对巨细胞病毒的活性不如更昔洛韦，但它提供了一种新的结构原型，可在此基础上进行研究以发现针对这些病毒类型的新药物。
