β-内酰胺类化合物的紫外光化学合成研究
发布时间：2018-08-15 11:29
【摘要】：在大量临床使用的抗生素的核心结构中发现一种四元环骨架:β-内酰胺,是合成氨基酸,生物碱和紫杉烷的重要中间体。众所周知,β-内酰胺环是有价值的结构单元、药理活性分子和生物活性天然/非天然化合物的重要合成物,因此,已有大量文献对β-内酰胺合成的进行了报道。迄今为止,文献所报道的构建β-内酰胺环的方法往往反应条件苛刻,步骤复杂。虽然反应原料简单易得,但该反应过程必须经金属介导环化等步骤才能得到相对应的β-内酰胺,所以开发出绿色、环保、简单的工艺路线具有非常重要的经济和社会意义。本文探究了一类由甲基丙烯酰胺类化合物在紫外光诱导下发生分子内环化反应,为构建具有广泛生物活性和合成潜力的β-内酰胺类化合物结构开拓了一条新的途径。以N-烯丙基-N-(对甲基苯磺酰基)甲基丙烯酰胺化合物为反应物模板,探索最优反应条件为甲醇为溶剂,石英管为反应装置,300 nm紫外光为光源,浓度为0.005 mmol/mL,合成了24个甲基丙烯酰胺类衍生物,在最优条件下对反应普适性进行了探索,其中18个甲基丙烯酰胺类衍生物能够在紫外光诱导下获得β-内酰胺类化合物,并取得了低等到中等的收率。结合实验结果与相关文献,提出了可能的反应机理:在紫外光诱导下,烯丙基或异丙基上与N原子相连碳的σ键(即C(sp3)-H键)发生均裂产生氢原子,并发生1,5-氢迁移,然后该自由基结构经过一个四元环过渡态进行分子内环化反应得到目标产物:β-内酰胺类化合物。
[Abstract]:A quaternary ring skeleton, 尾 -lactam, is found in the core structure of a large number of clinically used antibiotics, which is an important intermediate for the synthesis of amino acids, alkaloids and taxanes. It is well known that 尾-lactam ring is a valuable structural unit, pharmacological active molecules and bioactive natural / non-natural compounds of important synthesis, therefore, there have been a lot of literature on the synthesis of 尾-lactam has been reported. Up to now, the methods reported in the literature for constructing 尾-lactam ring are often harsh and complicated. Although the raw materials are simple and easy to obtain, the reaction process must be metal-mediated cyclization in order to obtain corresponding 尾 -lactam, so the development of green, environmentally friendly and simple process has very important economic and social significance. In this paper, the intramolecular cyclization of a class of methacrylamide compounds induced by ultraviolet light has been investigated, which opens up a new way for the construction of 尾 -lactam compounds with wide biological activity and synthesis potential. Using N-allyl-N- (p-methylphenylsulfonyl) methacrylamides as template, the optimum reaction conditions are methanol as solvent, quartz tube as reaction device and UV light source at 300 nm. At a concentration of 0.005 mmol / mL, 24 methacrylamide derivatives were synthesized. Under the optimal conditions, the universality of the reaction was explored. Among them, 18 methyl acrylamide derivatives were able to obtain 尾 -lactam compounds under ultraviolet light. A low to medium yield was obtained. Combined with the experimental results and related literatures, the possible reaction mechanism was proposed: under UV light induction, the 蟽 bond (C (sp3) -H bond) linked to N atom on allyl or isopropyl group was homogeneously split to produce hydrogen atom, and the hydrogen transport occurred. Then the structure of the free radical was synthesized by the intramolecular cyclization of a transition state of the quaternary ring to obtain the target product: 尾-lactam compounds.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O624.6
本文编号：2184066
[Abstract]:A quaternary ring skeleton, 尾 -lactam, is found in the core structure of a large number of clinically used antibiotics, which is an important intermediate for the synthesis of amino acids, alkaloids and taxanes. It is well known that 尾-lactam ring is a valuable structural unit, pharmacological active molecules and bioactive natural / non-natural compounds of important synthesis, therefore, there have been a lot of literature on the synthesis of 尾-lactam has been reported. Up to now, the methods reported in the literature for constructing 尾-lactam ring are often harsh and complicated. Although the raw materials are simple and easy to obtain, the reaction process must be metal-mediated cyclization in order to obtain corresponding 尾 -lactam, so the development of green, environmentally friendly and simple process has very important economic and social significance. In this paper, the intramolecular cyclization of a class of methacrylamide compounds induced by ultraviolet light has been investigated, which opens up a new way for the construction of 尾 -lactam compounds with wide biological activity and synthesis potential. Using N-allyl-N- (p-methylphenylsulfonyl) methacrylamides as template, the optimum reaction conditions are methanol as solvent, quartz tube as reaction device and UV light source at 300 nm. At a concentration of 0.005 mmol / mL, 24 methacrylamide derivatives were synthesized. Under the optimal conditions, the universality of the reaction was explored. Among them, 18 methyl acrylamide derivatives were able to obtain 尾 -lactam compounds under ultraviolet light. A low to medium yield was obtained. Combined with the experimental results and related literatures, the possible reaction mechanism was proposed: under UV light induction, the 蟽 bond (C (sp3) -H bond) linked to N atom on allyl or isopropyl group was homogeneously split to produce hydrogen atom, and the hydrogen transport occurred. Then the structure of the free radical was synthesized by the intramolecular cyclization of a transition state of the quaternary ring to obtain the target product: 尾-lactam compounds.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O624.6
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