Ravindra Babu B, Sørensen Mads D, Parmar Virinder S, Harrit Niels H, Wengel Jesper
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Org Biomol Chem. 2004 Jan 7;2(1):80-9. doi: 10.1039/b310719a. Epub 2003 Dec 1.
Synthesis of 2[prime or minute]-O,4[prime or minute]-C-methylene-[small alpha]-l-ribofuranosyl derivatives containing phenyl and 1-pyrenyl aglycons, i.e., novel [small alpha]-l-ribo configured LNA-type C-aryl nucleosides, has been accomplished. Key synthetic steps included stereoselective Grignard reactions on tetrahydrofuran aldehyde, configurational inversion of the resulting alcohol into alcohol, and concomitant Mitsonobu cyclization furnishing the desired bicyclic furanosyl skeleton with a locked conformation. The phosphoramidite derivatives and were used for automated synthesis of 9-mer DNA and [small alpha]-L-LNA oligonucleotides containing the [small alpha]-L-LNA-type C-aryl monomers ([small alpha]L)Ph(L) and ([small alpha]L)Py(L) containing a phenyl and pyrenyl aglycon, respectively. Thermal denaturation studies showed universal base pairing behavior for the pyrenyl monomer ([small alpha]L)Py(L) when incorporated into a DNA or an [small alpha]-L-LNA oligonucleotide.
已完成含苯基和1-芘基糖苷配基的2'-O,4'-C-亚甲基-α-L-呋喃核糖基衍生物（即新型α-L-核糖构型的LNA型C-芳基核苷）的合成。关键合成步骤包括对四氢呋喃醛进行立体选择性格氏反应、将所得醇的构型转化为醇，以及伴随的 Mitsonobu 环化反应，从而提供具有锁定构象的所需双环呋喃糖骨架。亚磷酰胺衍生物用于自动合成分别含苯基和芘基糖苷配基的9聚体DNA和含α-L-LNA型C-芳基单体([αL)Ph(L)和([αL)Py(L)]的α-L-LNA寡核苷酸。热变性研究表明，芘基单体([αL)Py(L)]掺入DNA或α-L-LNA寡核苷酸时具有通用碱基配对行为。
