以肌苷为原料合成水粉蕈素

The Synthesis of Nebularine from Inosine

摘要:

以肌苷为原料，通过乙酰化和氯代反应，得到2′,3′,5′-三-O-乙酰基-6-氯嘌呤核苷，继而和三苯基膦反应，得到2′,3′,5′-三-O-乙酰基-6-三苯基膦嘌呤核苷，最后在碳酸钾作用下断裂C—P键，同时脱掉乙酰基，以4步和62%的总收率得到产物水粉蕈素。考察了关键反应步骤C—P键的生成和断裂对产物收率的影响，得到了最佳的反应条件。反应规模可以扩大到200 g。以重水和氘代甲醇为混合反应溶剂，以76%的单步收率得到6-氘代水粉蕈素。

Abstract:

2′,3′,5′-Tri-O-acetyl-6-chloropurine nucleoside was obtained from inosine via acetylation and chlorination. Then, 2′,3′,5′-tri-O-acetyl-6-chloropurine nucleoside was transformed into 2′,3′,5′-tri-O-acetyl-6-triphenylphosphonine nucleoside with triphenylphosphine. Finally, C—P bond was cleavaged in the presence of K2CO3, and acetyl groups were removed simultaneously. The product Nebularine was obtained in 4 steps and 62% overall yield. The effects of the formation and cleavage of C—P bond on the yields were investigated, and the optimized reaction conditions were obtained. The reaction scale could be expanded to 200 g. 6-Deuterated Nebularine was obtained in 76% yield from 2′,3′,5′-tri-O-acetyl-6-triphenylphosphonine nucleoside in deuterated water and deuterated methanol.