Rovira Alexander R, Fin Andrea, Tor Yitzhak
Department of Chemistry and Biochemistry , University of California , San Diego , La Jolla , California 92093-0358 , USA . Email:
Chem Sci. 2017 Apr 1;8(4):2983-2993. doi: 10.1039/c6sc05354h. Epub 2017 Jan 30.
A series of emissive ribonucleoside purine mimics, all comprised of an isothiazolo[4,3-]pyrimidine core, was prepared using a divergent pathway involving a key Thorpe-Ziegler cyclization. In addition to an adenosine and a guanosine mimic, analogues of the noncanonical xanthosine, isoguanosine, and 2-aminoadenosine were also synthesized and found to be emissive. Isothiazolo 2-aminoadenosine, an adenosine surrogate, was found to be particularly emissive and effectively deaminated by adenosine deaminase. Competitive studies with adenosine deaminase with each analogue in combination with native adenosine showed preference for the native substrate while still deaminating the isothiazolo analogues.
通过一条涉及关键索普-齐格勒环化反应的发散性途径，制备了一系列均由异噻唑并[4,3 -]嘧啶核心组成的发射性核糖核苷嘌呤模拟物。除了腺苷和鸟苷模拟物外，还合成了非经典黄苷、异鸟苷和2 -氨基腺苷的类似物，并发现它们具有发射性。异噻唑并2 -氨基腺苷，一种腺苷替代物，被发现具有特别强的发射性，并且能被腺苷脱氨酶有效脱氨。用腺苷脱氨酶对每种类似物与天然腺苷进行的竞争性研究表明，尽管仍能使异噻唑并类似物脱氨，但该酶更倾向于天然底物。
