1,2,4-Diazaphosphole nucleosides. Synthesis, structure, and antitumor activity of nucleosides with a .lambda.3 phosphorus atom
作者:Timothy A. Riley、Steven B. Larson、Thomas L. Avery、Rick A. Finch、Roland K. Robins
DOI:10.1021/jm00164a016
日期:1990.2
pentasulfide gave 2',3',5'-tri-O-acetyl-1-beta-D-ribofuranosyl-1,2,4 lambda 3-diazaphosphole-3- thiocarboxamide (13). Deprotection with methanolic ammonia gave 1-beta-D-ribofuranosyl-1,2,4 lambda 3-diazaphosphole-3-thiocarboxamide (14). Compound 14 gave a 25% increase in life span (ILS) against L1210 in female BDF1 mice. The anomeric configuration and site of glycosylation of 5 and 13 were established
在路易斯酸催化的条件下,1,2,4λ3-二氮杂磷(4)的糖基化反应产生了唯一的产物1-α-D-呋喃核糖基1,2,4λ3-二氮杂磷(5)。通过将(氯次膦基)乙基(三甲基甲硅烷基)乙酸酯(8)与(三甲基甲硅烷基)重氮甲烷进行环缩合,然后用四正丁基氟化铵进行甲硅烷基化反应,合成1,2,4λ3-二氮杂磷-3-羧酸乙酯(10)。10在80℃下与氨甲醇反应,得到1,2,4λ3-二氮磷腈-3-羧酰胺。使用三氟甲磺酸三甲基甲硅烷基酯催化剂将10进行糖基化,然后进行氨解,得到了病毒唑(1)类似物1-β-D-核呋喃糖基-1,2,4λ3-二氮杂磷-3-甲酰胺(11)。将11乙酰化并随后用五硫化二磷处理得到2',3',5'-三-O-乙酰基-1-β-D-核呋喃糖基-1,2,4λ3-二氮杂磷酰基-3-硫代羧酰胺(13)。用甲醇氨脱保护得到1-β-D-呋喃呋喃糖基-1,2,4λ3-二氮杂磷基-3-硫代羧酰胺(14)。在