7-氮杂蝶啶的区域选择性糖基化以及7-氮杂蝶啶核苷向6-氮杂嘌呤核苷的转化。

Regioselective glycosylation of 7-azapteridines and conversion of the 7-azapteridine nucleosides into 6-azapurine nucleosides.

作者信息

Nagamatsu Tomohisa, Ma Jun, Akiba Shinya

机构信息

Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1, Tsushima-naka, Okayama 700-8530, Japan.

出版信息

Nucleic Acids Symp Ser (Oxf). 2008(52):561-2. doi: 10.1093/nass/nrn284.

DOI:10.1093/nass/nrn284

PMID:18776503

Abstract

The regioselective glycosylation of reumycins (3) reacted with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (4) and BSTFA in acetonitrile at 90 degrees C followed by reaction of SnCl(4) in dioxane at room temperature afforded the 1-(2',3',5'-tri-O-benzoyl-beta-D-ribofuranosyl)- 6-methylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-diones (5) (toxoflavin type nucleosides), while the similar alkylations with 1-bromo-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (6) and KHCO(3) in DMF at 100 degrees C gave predominantly the 8-(2',3',5'-tri-O-benzoyl-beta-D-ribofuranosyl)-6-methylpyrimido[5,4-e]-[1,2,4]triazine-5,7(6H,8H)-diones (7) (fervenulin type nucleosides). On the other hand, treatment of the 7-azapteridine nucleosides (5 and 7) in alkali solution at room temperature yielded the corresponding 1-(beta-D-ribofuranosyl)-5-methyl-1H-imidazo[4,5-e][1,2,4]- triazin-6(5H)-ones (8) and 7-(beta-D-ribofuranosyl)-5-methyl-5H-imidazo[4,5-e][1,2,4]triazin-6(7H)-ones (9) [6-azapurine nucleosides] by benzilic acid rearrangement. Some 7-azapteridine nucleosides (5 and 7-9) showed antitumor activities and anti-coccidiosis activities.

摘要

鲁霉素（3）与1-O-乙酰基-2,3,5-三-O-苯甲酰基-β-D-呋喃核糖（4）及BSTFA在乙腈中于90℃发生区域选择性糖基化反应，随后在室温下于二氧六环中与四氯化锡反应，得到1-(2',3',5'-三-O-苯甲酰基-β-D-呋喃核糖基)-6-甲基嘧啶并[5,4-e][1,2,4]三嗪-5,7(1H,6H)-二酮（5）（毒黄素型核苷），而在100℃下于N,N-二甲基甲酰胺中用1-溴-2,3,5-三-O-苯甲酰基-β-D-呋喃核糖（6）和碳酸氢钾进行类似的烷基化反应，则主要得到8-(2',3',5'-三-O-苯甲酰基-β-D-呋喃核糖基)-6-甲基嘧啶并[5,4-e]-[1,2,4]三嗪-5,7(6H,8H)-二酮（7）（热情菌素型核苷）。另一方面，7-氮杂蝶啶核苷（5和7）在室温下于碱性溶液中处理，通过二苯乙醇酸重排得到相应的1-(β-D-呋喃核糖基)-5-甲基-1H-咪唑并[4,5-e][1,2,4]-三嗪-6(5H)-酮（8）和7-(β-D-呋喃核糖基)-5-甲基-5H-咪唑并[4,5-e][1,2,4]三嗪-6(7H)-酮（9）[6-氮杂嘌呤核苷]。一些7-氮杂蝶啶核苷（5和7 - 9）显示出抗肿瘤活性和抗球虫活性。