Poon Kevin W C, Liang Ningning, Datta Apurba
Department of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas, USA.
Nucleosides Nucleotides Nucleic Acids. 2008 Apr;27(4):389-407. doi: 10.1080/15257770801944394.
A stereoselective synthetic route has been developed for the combinatorial synthesis of a structurally unique class of C-4' side chain modified peptide-linked nucleosides. The synthetic strategy and approach involves initial synthesis of a strategically functionalized amino butenolide template, utilizing L-serine as a chiral starting material. Subsequent transformation of the above lactone to C4' aminoalkyl substituted nucleosides, followed by the peptidic coupling of the C4' side chain amine with various amino acids completed the syntheses of the target peptidyl nucleosides. Employing the above route, and utilizing a combination of easily available nucleobases (4) and amino acids (6) as the two diversity elements, synthesis of a 24-member combinatorial library of the title peptide-linked nucleosides has been accomplished.
已开发出一种立体选择性合成路线，用于组合合成一类结构独特的C-4'侧链修饰的肽连接核苷。合成策略和方法包括以L-丝氨酸为手性起始原料，初步合成一个经过策略性功能化的氨基丁烯内酯模板。随后将上述内酯转化为C4'氨基烷基取代的核苷，接着将C4'侧链胺与各种氨基酸进行肽偶联，从而完成目标肽基核苷的合成。采用上述路线，并利用易于获得的核苷碱基（4种）和氨基酸（6种）作为两种多样性元素，已完成了标题肽连接核苷的24元组合文库的合成。
