Fehring Volker, Knights Sally, Chan Mai-Yee, O'Neil Ian A, Cosstick Richard
Department of Chemistry, University of Liverpool, Crown St., Liverpool, UK L69 7ZD.
Org Biomol Chem. 2003 Jan 7;1(1):123-8. doi: 10.1039/b208786n.
The ability of 2'-alpha-C-carboxyalkyl nucleosides to undergo an unusual two-step stereocontrolled nucleobase exchange process has been investigated. Upon silylation a protected 2'-deoxy-2'-alpha-C-(carboxymethyl)uridine derivative can undergo intramolecular displacement of the uracil base, by the 2'-carboxylic acid group, to form a pentofuranosyl gamma-lactone. Under identical conditions the homologous 2'-deoxy-2'-alpha-C-(carboxyethyl)uridine derivative does not yield the corresponding delta-lactone, but undergoes elimination of uracil to give the corresponding glycal. The pentofuranosyl gamma-lactone is a good substrate for nucleoside synthesis by the Vorbrüggen procedures and undergoes completely stereoselective ring opening with either pyrimidine or purine silylated nucleobases to give novel 2'-C-carboxymethyl beta-nucleosides in moderate to high yield.
对2'-α-C-羧烷基核苷进行异常的两步立体控制碱基交换过程的能力进行了研究。在硅烷化后，一种受保护的2'-脱氧-2'-α-C-(羧甲基)尿苷衍生物可通过2'-羧酸基团进行尿嘧啶碱基的分子内取代，形成戊呋喃糖基γ-内酯。在相同条件下，同源的2'-脱氧-2'-α-C-(羧乙基)尿苷衍生物不会产生相应的δ-内酯，而是发生尿嘧啶消除反应生成相应的烯糖。戊呋喃糖基γ-内酯是通过Vorbrüggen方法进行核苷合成的良好底物，并且与嘧啶或嘌呤硅烷化碱基进行完全立体选择性的开环反应，以中等至高收率得到新型的2'-C-羧甲基β-核苷。
