通过化学和生物转化方法合成4-氨基和5-氨基-1-(2-脱氧-D-赤藓糖基)咪唑核苷

Synthesis of 4- and 5-amino-1-(2-deoxy-D-erythro-pentofuranosyl)imidazole nucleosides by chemical and biotransformation methods.

作者信息

Ewing D F, Holý A, Votruba I, Humble R W, Mackenzie G, Hewedi F, Shaw G

机构信息

School of Chemistry, University of Hull, Great Britain.

出版信息

Carbohydr Res. 1991 Sep 2;216:109-18. doi: 10.1016/0008-6215(92)84154-k.

DOI:10.1016/0008-6215(92)84154-k

PMID:1797375

Abstract

(2-Deoxy-D-erythro-pentofuranosyl)imidazole nucleosides have been synthesised by glycosylation of the sodium salt of ethyl 5-aminoimidazole-4-carboxylate with 2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranosyl chloride. Glycosylation of ethyl 5-aminoimidazole-4-carboxylate with 2-deoxy-beta-D-erythro-pentofuranose was also achieved enzymically using E. coli, immobilised by ionotropic gelation in an alginate gel, with 2'-deoxyuridine as glycosyl donor. 5-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)imidazole-4-carboxylic acid 5'-phosphate and 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)imidazole-5-carboxylic acid 5'-phosphate were synthesised by phosphorylation of the respective nucleosides and examined as inhibitors of phosphoribosylaminoimidazole carboxylase (EC 4.1.1.21) and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (EC 6.3.2.6), which are involved in the de novo biosynthesis of purine nucleotides.

摘要

（2-脱氧-D-赤藓糖基）咪唑核苷是通过5-氨基咪唑-4-羧酸乙酯钠盐与2-脱氧-3,5-二-O-对甲苯甲酰基-α-D-赤藓糖基氯进行糖基化反应合成的。利用离子凝胶法固定在藻酸盐凝胶中的大肠杆菌，以2'-脱氧尿苷作为糖基供体，还实现了5-氨基咪唑-4-羧酸乙酯与2-脱氧-β-D-赤藓糖的酶促糖基化反应。通过对相应核苷进行磷酸化反应合成了5-氨基-1-（2-脱氧-β-D-赤藓糖基）咪唑-4-羧酸5'-磷酸酯和4-氨基-1-（2-脱氧-β-D-赤藓糖基）咪唑-5-羧酸5'-磷酸酯，并将其作为嘌呤核苷酸从头生物合成中涉及的磷酸核糖氨基咪唑羧化酶（EC 4.1.1.21）和磷酸核糖氨基咪唑琥珀酰胺羧酰胺合成酶（EC 6.3.2.6）的抑制剂进行了研究。