Matysiak Stefan, Waldscheck Bernhard, Pfleiderer Wolfgang
Fachbereich Chemie, Universität Konstanz, Konstanz, Germany.
Nucleosides Nucleotides Nucleic Acids. 2004;23(1-2):51-66. doi: 10.1081/ncn-120027817.
A general synthetic approach to various isoxanthopterin-nucleosides starting from 6-methyl-2-methylthio-4(3H),7(8H)-pterdinedione (1) has been developed. Ribosylation with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose via the silyl-method led to 2 and reaction with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-ribofuranose using the DBU-method afforded 28. Protection of the amide function at O4 by benzylation to 5 and by a Mitsunobu reaction with 2-(4-nitrophenyl)ethanol to 29 gave soluble intermediates which can be oxidized to the corresponding 2-methylsulfonyl derivatives 8 and 30, respectively. Nucleophilic displacement reactions of the highly reactive 2-methylsulfonyl functions by various amines proceeded under mild conditions to isoxanthopterin-N8-ribo- (11-17) and 2'-deoxyribomucleosides (31-33). Debenzylation can be achieve by Pd-catalyzed hydrogenation (9 to 19) and cleavage of the npe-protecting group (31, 32 to 34, 35) works well with DBU by beta-elimination.
已开发出一种从6-甲基-2-甲硫基-4(3H),7(8H)-蝶啶二酮(1)出发合成各种异黄蝶呤核苷的通用方法。通过硅烷基法用1-O-乙酰基-2,3,5-三-O-苯甲酰基-β-D-呋喃核糖进行核糖基化反应得到2，使用DBU法与1-氯-2-脱氧-3,5-二-O-对甲苯甲酰基-α-D-呋喃核糖反应得到28。通过苄基化将O4处的酰胺官能团保护为5，并通过与2-(4-硝基苯基)乙醇的Mitsunobu反应得到29，得到可溶中间体，其可分别氧化为相应的2-甲基磺酰基衍生物8和30。各种胺对高活性2-甲基磺酰基官能团的亲核取代反应在温和条件下进行，生成异黄蝶呤-N8-核糖核苷(11-17)和2'-脱氧核糖核苷(31-33)。脱苄基反应可通过钯催化的氢化反应实现(9至19)，npe保护基团的裂解(31、32至34、35)通过DBU的β-消除反应效果良好。
