文献类型：期刊文献

中文题名：以鸟苷为原料合成海绵核苷

英文题名：The synthesis of spongosine from guanosine

作者：孙莉萍[1];杨政楠[2];高雪瑞[2];马国扬[2];夏然[2];徐绍红[2]

机构：[1]新乡学院生命科学与基础医学学院,河南新乡453003;[2]新乡学院药学院,河南新乡453003

第一机构：新乡学院

年份：2022

卷号：38

期号：4

起止页码：283-290

中文期刊名：分子科学学报

外文期刊名：Journal of Molecular Science

收录：CSTPCD;;北大核心:【北大核心2020】；

基金：国家自然科学基金资助项目(21602189);河南省高等学校青年骨干教师培养计划资助项目(2020GGJS248);大学生创新创业训练国家级项目(202011071011).

语种：中文

中文关键词：海绵核苷;鸟苷;重氮化反应;核苷合成

外文关键词：spongosine;guanosine;diazotization;nucleoside synthesis

摘要：本文报道了以鸟苷为原料合成海绵核苷的新方法.价格低廉的鸟苷用乙酰基保护糖环上的羟基后和POCl_(3)反应,将6位羰基转化为6-Cl,继而在亚硝酸叔丁酯作用下发生重氮化反应,将2-NH_(2)转化为2-OH,2-OH再和CH_(3)I反应使之甲基化,最后在饱和的NH_(3)/CH_(3)OH溶液中将6-Cl氨解为6-NH_(2),同时脱除乙酰基,以5步和52%的总收率得到海绵核苷.该方法原料廉价易得,反应规模可以扩大到200 g,解决了传统方法中原料价格高的问题,具有一定的应用前景.
The isolation and purification from sponge was once the only way to obtain spongosine,and then chemical synthesis methods were developed.The first chemical synthesis method used adenosine as starting substrate with leaving group(such as NO_(2),C and SCH_(3),etc)at 2-position in the presence of NaOCH_(3).However,the starting material 2-substituted purine was difficult to synthesize and the cost was high,which limited the expansion of the reaction scale.The second chemical synthesis was relied on the condensation of 2-methoxyadenine and tetraacetylribose.The disadvantage of this method was the use of toxic and harmful heavy metal salts,such as SnCl_(4) and HgCl_(2),etc.The synthesis of spongosine from cheap and easily available starting materials can avoid the tedious steps of separation and extraction from a large number of marine organisms,and can also solve the problems of limited sources of starting materials and heavy metal residues in chemical synthesis.Guanosine is a basic raw material in the field of nucleoside chemistry with low price(market price<100 yuan·kg^(-1)).In this paper,a new method for the synthesis of spongosine from guanosine was reported by 5-step synthesis with 52%total yield.The first step:guanosine was protected by acetyl groups in acetic anhydride in the presence of DMAP to give 2',3',5'-tri-O-acetyl gunosine in 93%yield.The second step:6-carbonyl group of 2',3',5'-tri-O-acetyl gunosine was converted into 6-Cl by POCl_(3)in MeCN affording 6-chloro-2',3',5'-tri-O-acetyl guanosine in 90%yield.The third step:the diazotization of 2-NH_(2)to 6-OH was carried out with t-butyl nitrite in 78%yield.The fourth step:2-hydroxyl-6-chloro-9-(2',3',5'-tri-O-acetyl)-β-D-ribofuranosyl purine was methylated with CH_(3)I in the presence of Cs_(2)CO_(3) in MeCN in 89%yield.The fifth step:6-Cl of 2-methyoxyl-6-chloro-9-(2',3',5'-tri-O-acetyl)-β-D-ribofuranosyl purine was ammonolysized to-NH_(2)in saturated NH_(3)/CH_(3)OH solution,and acetyl groups were removed simultaneously in 90%yield.The reaction scale could be expanded to 200 g in good yields,which made this route more attractive for industrial application.Spongosine could be transformed into many nucleosides vīa chemical reactions.