Kazimierczuk Z, Stolarski R, Shugar D
Acta Biochim Pol. 1984;31(1):33-48.
A number of acyclo nucleosides of benzimidazole derivatives has been synthesized, in which the benzimidazole ring includes substituents at C(5), C(6) and C(2). The acyclic chains which replace the sugar moiety are 2',3'-dihydroxypropyl, 2'-hydroxyethoxymethyl and 1',5'-dihydroxy-4'-hydroxymethyl-3'- oxypentyl -2' (R), each of which corresponds to some fragment of the ribose ring. 1H NMR spectroscopy has been employed to determine the conformations of these acyclic chains in solutions of fully deuterated dimethylsulfoxide and methanol, utilizing for this purpose vicinal proton-proton coupling constants, and the new Karplus relation developed by Haasnoot , de Leeuw & Altona ( Tetrahedron , 36, 2783-2792, 1980). The data thus obtained are compared with those available for the solid state from X-ray diffraction data, and should be applicable to other classes of acyclonucleosides . Nucleotides of the three types of acyclo benzimidazole nucleosides have also been prepared, and their susceptibilities to snake venom 5'-nucleotidase examined. In contrast to acycloG , the nucleoside analogues did not exhibit significant in vitro activity against herpes simplex virus type 1 or influenza virus.
已合成了多种苯并咪唑衍生物的无环核苷，其中苯并咪唑环在C(5)、C(6)和C(2)处含有取代基。取代糖部分的无环链分别为2',3'-二羟丙基、2'-羟基乙氧基甲基和1',5'-二羟基-4'-羟甲基-3'-氧代戊基-2'（R），每一种都与核糖环的某些片段相对应。利用邻位质子-质子耦合常数以及哈斯诺特、德·利乌和阿尔托纳（《四面体》，36，2783 - 2792，1980）提出的新卡尔普斯关系式，通过1H NMR光谱法测定了这些无环链在全氘代二甲亚砜和甲醇溶液中的构象。将由此获得的数据与从X射线衍射数据得到的固态数据进行比较，并且这些数据应适用于其他类别的无环核苷。还制备了三种类型的无环苯并咪唑核苷的核苷酸，并检测了它们对蛇毒5'-核苷酸酶的敏感性。与无环鸟苷不同，这些核苷类似物对1型单纯疱疹病毒或流感病毒没有显著的体外活性。
