【摘要】：在大量臨床使用的抗生素的核心結(jié)構(gòu)中發(fā)現(xiàn)一種四元環(huán)骨架:β-內(nèi)酰胺,是合成氨基酸,生物堿和紫杉烷的重要中間體。眾所周知,β-內(nèi)酰胺環(huán)是有價(jià)值的結(jié)構(gòu)單元、藥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,已有大量文獻(xiàn)對(duì)β-內(nèi)酰胺合成的進(jìn)行了報(bào)道。迄今為止,文獻(xiàn)所報(bào)道的構(gòu)建β-內(nèi)酰胺環(huán)的方法往往反應(yīng)條件苛刻,步驟復(fù)雜。雖然反應(yīng)原料簡(jiǎn)單易得,但該反應(yīng)過(guò)程必須經(jīng)金屬介導(dǎo)環(huán)化等步驟才能得到相對(duì)應(yīng)的β-內(nèi)酰胺,所以開(kāi)發(fā)出綠色、環(huán)保、簡(jiǎn)單的工藝路線具有非常重要的經(jīng)濟(jì)和社會(huì)意義。本文探究了一類由甲基丙烯酰胺類化合物在紫外光誘導(dǎo)下發(fā)生分子內(nèi)環(huán)化反應(yīng),為構(gòu)建具有廣泛生物活性和合成潛力的β-內(nèi)酰胺類化合物結(jié)構(gòu)開(kāi)拓了一條新的途徑。以N-烯丙基-N-(對(duì)甲基苯磺酰基)甲基丙烯酰胺化合物為反應(yīng)物模板,探索最優(yōu)反應(yīng)條件為甲醇為溶劑,石英管為反應(yīng)裝置,300 nm紫外光為光源,濃度為0.005 mmol/mL,合成了24個(gè)甲基丙烯酰胺類衍生物,在最優(yōu)條件下對(duì)反應(yīng)普適性進(jìn)行了探索,其中18個(gè)甲基丙烯酰胺類衍生物能夠在紫外光誘導(dǎo)下獲得β-內(nèi)酰胺類化合物,并取得了低等到中等的收率。結(jié)合實(shí)驗(yàn)結(jié)果與相關(guān)文獻(xiàn),提出了可能的反應(yīng)機(jī)理:在紫外光誘導(dǎo)下,烯丙基或異丙基上與N原子相連碳的σ鍵(即C(sp3)-H鍵)發(fā)生均裂產(chǎn)生氫原子,并發(fā)生1,5-氫遷移,然后該自由基結(jié)構(gòu)經(jīng)過(guò)一個(gè)四元環(huán)過(guò)渡態(tài)進(jìn)行分子內(nèi)環(huán)化反應(yīng)得到目標(biāo)產(chǎn)物:β-內(nèi)酰胺類化合物。
[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.
【學(xué)位授予單位】：哈爾濱工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O624.6

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本文編號(hào)：2184066