【作者】 冯伟；

【导师】 夏吾炯；

【作者基本信息】 哈尔滨工业大学 ， 物理化学， 2012， 硕士

【摘要】 由于环戊基碳环核苷具有很好的生物活性和抗病毒性，是很好的药物前驱体，而且环戊基的合成很具有挑战性，因此无论从药物开发还是方法学角度出发，探索环戊基碳环核苷新的合成路线都具有重要的意义和价值。本文旨在探索Norrish Ⅱ型光化学反应作为关键步合成环戊基碳环核苷的新方法。本文主要探索二环[3.1.0]己基酮羰基衍生物的液相光化学和固相不对称光化学的行为以及利用液相光化学底物合成环戊基（环戊烷基和环戊烯基）碳环核苷假糖基。首先以二环庚二烯为起始原料，经过七步反应得到液相光化学底物。液相光照条件下，反应时间延长，二级光化学反应加剧，裂解产率降低。固相光照条件下，反应时间和反应温度会对裂解产率和产物的ee产生影响，ee值最高达到75%。然后以液相光化学产物为原料，经过催化氢化、NaBH4还原、弱酸条件下脱水、氧化双键断链、LiAlH4还原和3%HCl甲醇体系脱保护得到环戊烷基碳环核苷假糖基；液相光化学底物经过双键氧化、叉丙酮保护、NaBH4还原、醇羟基溴代、DBU消除、氧化双键断链、NaBH4还原和TBAF/THF体系脱保护，得到环戊烯基碳环核苷假糖基。本文实现了利用Norrish Ⅱ型光化学合成环戊基碳环核苷假糖基的目的，对探索环戊基碳环核苷新的合成方法具有指导意义。更多还原

【Abstract】 Cyclopentyl carbocyclic nucleosides have good biological activity anddisease-resistance toxicity and they are good drug precursors. Therefore, in terms ofdrug development or methodological perspective, it is important and valuable forexploring new synthetic route of cyclopentyl carbocyclic nucleosides. This thesisaims to explore the new synthesis routes of the Norrish Ⅱtype photochemicalreaction as the key step to synthesize cyclopentyl carbocyclic nucleosides.Ⅰn this thesis, we focused on exploration of liquid-phase and solid-phaseasymmetric photochemical behavior of bicyclo [3.1.0] hexyl ketone carbonylderivatives and synthesis of cyclopentyl carbocyclic nucleosides pseudo sugar withthe liquid-phase photochemical product.Firstly, the solution photochemical substrate have been synthesized afterseven-step reactions taking the2,5-norbornadiene as the starting material. Under theliquid-phase, the secondary photochemical reaction intensified as prolonging thereaction time and the cleavage production rate reducing. Under the solid-phase, thereaction time and reaction temperature can influence the cleavage production rateand the ee value of the cleavage product. The ee value is up to75%.Secondly, cyclopentanyl carbocyclic nucleosides pseudo sugar have beensynthesized after five-step reactions from the solution product: catalytichydrogenation, NaBH4reduction, dehydration under weakly acidic conditions,oxidation of the double bond scission, LiAlH4reduction and deprotection with3%HCl methanol; Also, using the solution product as starting material, cyclopentenylcarbocyclic nucleosides pseudo sugar have been synthesized after eight-stepreactions: double bond oxidation, fork acetone protection, NaBH4reduction, alcoholhydroxyl bromide, elimination with DBU, oxidation of the double bond scission,NaBH4reduction and deprotection with TBAF.This thesis realized the purpose of synthesizing cyclopentyl carbocyclicnucleosides pseudo sugar with Norrish Ⅱtype photochemical reaction as the keystep, which is instructive to explore the new synthetic routes of cyclopentylcarbocyclic nucleosides.更多还原