Christensen Nanna K, Andersen Ann Katrine L, Schultz Trine R, Nielsen Poul
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, 5230 Odense M, Denmark.
Org Biomol Chem. 2003 Nov 7;1(21):3738-48. doi: 10.1039/b307667a.
Two [3.2.0]bicyclic nucleosides, 35 and 34, with one and two hydroxymethyl substituents, respectively, have been efficiently synthesized. A protected (3'-C-vinyl-beta-D-allofuranosyl)thymine derivative 28 was easily prepared from diacetone-D-glucose and the thymine moiety was protected with a BOM-group. After the introduction of a leaving group in the 2'-position, the subsequent nucleoside 31 was used as the substrate for a stereoselective dihydroxylation and a regioselective oxetane ring-formation to give after deprotection the bicyclic nucleoside 34. The surprisingly efficient formation of an oxetane was first discovered by serendipity on a corresponding methylfuranoside derivative. The allo-configured bicyclic nucleoside 34 was easily shortened to a ribo-configured analogue 35 by a diol-cleaving reaction and subsequent reduction. Both 34 and 35 are conformationally restricted in the important intermediate 04'-endo conformation.
两种[3.2.0]双环核苷，35和34，分别带有一个和两个羟甲基取代基，已被高效合成。一种受保护的(3'-C-乙烯基-β-D-阿洛呋喃糖基)胸腺嘧啶衍生物28可由双丙酮-D-葡萄糖轻松制备，胸腺嘧啶部分用BOM基团保护。在2'-位引入离去基团后，随后的核苷31用作立体选择性二羟基化和区域选择性氧杂环丁烷环形成的底物，脱保护后得到双环核苷34。氧杂环丁烷的惊人高效形成最初是在相应的甲基呋喃糖苷衍生物上偶然发现的。通过二醇裂解反应和随后的还原，具有阿洛构型的双环核苷34很容易缩短为具有核糖构型的类似物35。34和35在重要的中间体O4'-内型构象中都受到构象限制。
