Synthesis of 1-(2′-O-methyl-β-d-ribofuranosyl)-5-nitroindole and its phosphoramidite derivative

The synthesis of 1-(2′-O-methyl-β-d-ribofuranosyl)-5-nitroindole, a new nucleoside containing the universal base 5-nitroindole, and its phosphoramidite derivative for incorporation into oligonucleotides is described.     

RNA化学合成中的保护基

近几年来, RNA的化学合成有了较大进展, 本文讨论了RNA化学合成过程中的保护基问题,着重介绍了核糖核苷的2'-和3'-位羟基的选择性保护方法。     

HP 8451 A二极管阵列分光光度计用于混合核苷和碱基的HPLC分析

当代医药学的发展根据分子结构原理,研制出一大类的核酸药物。天然的核苷和核苷酸是合成核酸类药物的基本原料,目前有两条生产路线,一是从酵母核糖核酸经化学法或酶法进行水解制取,可得到分别含腺嘌呤,鸟嘌呤、胞嘧啶、尿嘧啶碱基的四种核苷或四种核苷酸;二是用发酵法分别直接得到特定的核苷     

7‐Iodo‐5‐aza‐7‐deazaguanine ribonucleoside: crystal structure,physical properties,base‐pair stability and functionalization

The positional change of nitrogen‐7 of the RNA constituent guanosine to the bridgehead position‐5 leads to the base‐modified nucleoside 5‐aza‐7‐deazaguanosine. Contrary to guanosine, this molecule cannot form Hoogsteen base pairs and the Watson–Crick proton donor site N3—H becomes a proton‐acceptor site. This causes changes in nucleobase recognition in nucleic acids and has been used to construct stable `all‐purine' DNA and DNA with silver‐mediated base pairs. The present work reports the single‐crystal X‐ray structure of 7‐iodo‐5‐aza‐7‐deazaguanosine, C<sub>10</sub>H<sub>12</sub>IN<sub>5</sub>O<sub>5</sub> ( 1 ). The iodinated nucleoside shows an anti conformation at the glycosylic bond and an N conformation (O4′‐endo) for the ribose moiety, with an antiperiplanar orientation of the 5′‐hydroxy group. Crystal packing is controlled by interactions between nucleobase and sugar moieties. The 7‐iodo substituent forms a contact to oxygen‐2′ of the ribose moiety. Self‐pairing of the nucleobases does not take place. A Hirshfeld surface analysis of 1 highlights the contacts of the nucleobase and sugar moiety (O—H…O and N—H…O). The concept of pK‐value differences to evaluate base‐pair stability was applied to purine–purine base pairing and stable base pairs were predicted for the construction of `all‐purine' RNA. Furthermore, the 7‐iodo substituent of 1 was functionalized with benzofuran to detect motional constraints by fluorescence spectroscopy.     

Two‐Photon‐Induced Fluorescence of Isomorphic Nucleobase Analogs

Five isomorphic fluorescent uridine mimics have been subjected to two‐photon (2P) excitation analysis to investigate their potential applicability as non‐perturbing probes for the single‐molecule detection of nucleic acids. We find that small structural differences can cause major changes in the 2P excitation probability, with the 2P cross sections varying by over one order of magnitude. Two of the probes, both thiophene‐modified uridine analogs, have the highest 2P cross sections (3.8 GM and 7.6 GM) reported for nucleobase analogs, using a conventional Ti:sapphire laser for excitation at 690 nm; they also have the lowest emission quantum yields. In contrast, the analogs with the highest reported quantum yields have the lowest 2P cross sections. The structure‐photophysical property relationship presented here is a first step towards the rational design of emissive nucleobase analogs with controlled 2P characteristics. The results demonstrate the potential for major improvements through judicious structural modifications.     

2′,3′-O-二苯甲酰尿嘧啶核糖核苷U(BZ)_2单晶的制备和晶体结构测定

制备了2＇,3＇-O-二苯甲酰基尿嘧啶核糖核苷U(BZ)_2,并在DMF溶液中培养得到单晶。单晶经X射线衍射测定,属三斜晶系,空间群为Pl。晶胞参数a=5.734(1)(?),b=10.124(3)(?),c=11.905(3)(?),α=73.07(2)°,β=84.36(2)°,γ=81.61(2)°,Z=1。用CAD-4四圆衍射仪收集衍射数据。用直接法解晶体结构,用块对角矩阵最小二乘法修正,对3154个独立反射,最终R=0.070。U(BZ)_2的碱基相对于糖环为β构型,两个苯甲酰基在空间上远离5＇-OH,使5＇-OH周围空隙较大,因而苯甲酰基作为Ur的2＇,3＇-羟基的保护基,对5＇-OH的反应不存在立体障碍。