新型异斯特维醇衍生物的合成及其不对称催化性能研究
发布时间：2019-02-13 15:28
【摘要】：本论文以天然产物甜菊糖苷衍生而来具有刚性骨架的贝叶烷型四环二萜类化合物异斯特维醇(Isosteviol)为先导化合物，通过酯化、羟甲基化、肟化、氧化、还原等反应对其进行结构修饰和改造，在其骨架上引入羟基、肟基、杂环、硫脲、以及α，β不饱和羰基等活性基团，共合成出27个新型异斯特维醇功能取代衍生物，其中16个是未见于文献报道的新化合物。所得新化合物的结构经IR、1HNMR、13CNMR和HRMS表征。考察了羟基硫脲类异斯特维醇衍生物作为小分子催化剂对不对称Petasis反应的催化活性和立体选择性。合成了一系列异斯特维醇衍生的新型手性二齿配体，用UV-Vis光谱考察了其对不同金属离子的配位性能，研究了手性配体存在下金属离子对不对称Henry反应的催化性能。具体研究工作如下： 一、C环扩环异斯特维醇衍生物的合成 以甜菊糖苷为原料，在酸性条件下水解重排得到异斯特维醇，经过酯化和羟甲基化反应得到15α-羟甲基-16β-羟基异斯特维醇乙酯。然后经对甲苯磺酰氯取代、碱性消除得到化合物6，在三氟化硼催化作用下与苯胺反应得到重排扩环产物7，后者SeO2对烯丙位氧化得到含有羟基的苯胺取代的C环扩环衍生物8。 二、15-α-羟甲基16-α-取代硫脲基异斯特维醇衍生物的合成及其对不对称Petasis反应的催化性能研究 化合物6转化成相应醛肟10后，在三氟化硼催化下发生分子内1，3-偶极加成生成恶唑烷衍生物11，后者在雷尼镍催化下氢化开环得到15-α-羟甲基16-α-氨基异斯特维醇衍生物16。化合物16与取代的异硫氰酸苯酯反应得到9种15-α-羟甲基16-α-取代硫脲基异斯特维醇衍生物。考察了化合物15作为手性有机小分子催化剂对不对称Petasis反应的催化活性和立体选择性。 三、15-α-羟甲基16-α-取代氨基异斯特维醇手性配体的合成及其金属配位催化性能研究 15-α-羟甲基16-α-氨基异斯特维醇衍生物16与水杨醛或吡啶甲醛反应得到相应的亚胺25和27，25经硼氢化钠还原得到含有羟基、取代胺基的异斯特维醇衍生物26。用UV-Vis谱考察了各化合物分别与不同金属离子的配位性能及其对不对称Henry反应中的催化活性和立体选择性。
[Abstract]:In this paper, isostavitol (Isosteviol) with rigid skeleton derived from the natural product stevioside was used as the leading compound by esterification, hydroxylation, oximation, oxidation, esterification, hydroxylation, oximation, oxidation, esterification, hydroxylation, oximation and oxidation. The structure was modified and modified by reduction reaction. The active groups such as hydroxyl group, oxime group, heterocyclic group, thiourea group and 伪, 尾 unsaturated carbonyl group were introduced into the skeleton to synthesize 27 new functional substituents of isostavitol. Sixteen of them are new compounds not reported in the literature. The structure of the new compounds was characterized by IR,1HNMR,13CNMR and HRMS. The catalytic activity and stereoselectivity of hydroxyl thiourea derivatives for asymmetric Petasis reaction were investigated. A series of novel chiral didentate ligands derived from isostavitol were synthesized. Their coordination properties for different metal ions were investigated by UV-Vis spectroscopy. The catalytic properties of metal ions for asymmetric Henry reaction in the presence of chiral ligands were studied. The main works are as follows: 1. The synthesis of C ring extended isostratrol derivatives from stevioside was hydrolyzed and rearranged under acidic conditions to produce isosteravol. Ethyl 15 伪 -hydroxymethyl-16 尾 -hydroxyisosterol was synthesized by esterification and hydroxymethylation. Then the compound 6 was obtained by substitution of p-toluenesulfonyl chloride and alkalinity elimination. Under the catalysis of boron trifluoride and aniline, the product of rearrangement and ring expansion was obtained. The aniline substituted by hydroxyl aniline was synthesized by the SeO2 oxidation of allylic derivatives 8. Synthesis of bis, 15- 伪 -hydroxymethyl 16- 伪 -substituted thiourea isostavitol derivatives and their catalytic properties for asymmetric Petasis reaction; compound 6 was transformed into corresponding aldoxime 10. In the presence of boron trifluoride catalyzed intramolecular 1o 3- dipole addition, oxazolane derivatives 11 were synthesized, and the latter was hydrogenated to form 15- 伪 -hydroxymethyl 16- 伪 -aminoisosterol derivative 16- 伪 -hydroxymethyl 16- 伪 -aminoisosteryl alcohol under the catalytic hydrogenation of Raney nickel. Compound 16 reacted with substituted phenylethyl thiocyanate to obtain nine derivatives of 15- 伪 -hydroxymethyl 16- 伪 -substituted thiourea isostavitol. The catalytic activity and stereoselectivity of compound 15 as a small chiral organic catalyst for asymmetric Petasis reaction were investigated. Three Synthesis of chiral ligands of 15- 伪 -hydroxymethyl 16- 伪 -substituted aminoisostavitol and their catalytic properties for metal coordination; 15- 伪 -hydroxymethyl-16- 伪 -aminoisostavol derivative 16 and salicylidene or pyridine The corresponding imine 25 and 27o 25 were reduced by sodium borohydride to obtain hydroxyl groups from formaldehyde reaction. Substituted Amino Isostavitol Derivatives 26. The coordination properties of the compounds with different metal ions and their catalytic activity and stereoselectivity for asymmetric Henry reactions were investigated by UV-Vis spectroscopy.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914
本文编号：2421687
[Abstract]:In this paper, isostavitol (Isosteviol) with rigid skeleton derived from the natural product stevioside was used as the leading compound by esterification, hydroxylation, oximation, oxidation, esterification, hydroxylation, oximation, oxidation, esterification, hydroxylation, oximation and oxidation. The structure was modified and modified by reduction reaction. The active groups such as hydroxyl group, oxime group, heterocyclic group, thiourea group and 伪, 尾 unsaturated carbonyl group were introduced into the skeleton to synthesize 27 new functional substituents of isostavitol. Sixteen of them are new compounds not reported in the literature. The structure of the new compounds was characterized by IR,1HNMR,13CNMR and HRMS. The catalytic activity and stereoselectivity of hydroxyl thiourea derivatives for asymmetric Petasis reaction were investigated. A series of novel chiral didentate ligands derived from isostavitol were synthesized. Their coordination properties for different metal ions were investigated by UV-Vis spectroscopy. The catalytic properties of metal ions for asymmetric Henry reaction in the presence of chiral ligands were studied. The main works are as follows: 1. The synthesis of C ring extended isostratrol derivatives from stevioside was hydrolyzed and rearranged under acidic conditions to produce isosteravol. Ethyl 15 伪 -hydroxymethyl-16 尾 -hydroxyisosterol was synthesized by esterification and hydroxymethylation. Then the compound 6 was obtained by substitution of p-toluenesulfonyl chloride and alkalinity elimination. Under the catalysis of boron trifluoride and aniline, the product of rearrangement and ring expansion was obtained. The aniline substituted by hydroxyl aniline was synthesized by the SeO2 oxidation of allylic derivatives 8. Synthesis of bis, 15- 伪 -hydroxymethyl 16- 伪 -substituted thiourea isostavitol derivatives and their catalytic properties for asymmetric Petasis reaction; compound 6 was transformed into corresponding aldoxime 10. In the presence of boron trifluoride catalyzed intramolecular 1o 3- dipole addition, oxazolane derivatives 11 were synthesized, and the latter was hydrogenated to form 15- 伪 -hydroxymethyl 16- 伪 -aminoisosterol derivative 16- 伪 -hydroxymethyl 16- 伪 -aminoisosteryl alcohol under the catalytic hydrogenation of Raney nickel. Compound 16 reacted with substituted phenylethyl thiocyanate to obtain nine derivatives of 15- 伪 -hydroxymethyl 16- 伪 -substituted thiourea isostavitol. The catalytic activity and stereoselectivity of compound 15 as a small chiral organic catalyst for asymmetric Petasis reaction were investigated. Three Synthesis of chiral ligands of 15- 伪 -hydroxymethyl 16- 伪 -substituted aminoisostavitol and their catalytic properties for metal coordination; 15- 伪 -hydroxymethyl-16- 伪 -aminoisostavol derivative 16 and salicylidene or pyridine The corresponding imine 25 and 27o 25 were reduced by sodium borohydride to obtain hydroxyl groups from formaldehyde reaction. Substituted Amino Isostavitol Derivatives 26. The coordination properties of the compounds with different metal ions and their catalytic activity and stereoselectivity for asymmetric Henry reactions were investigated by UV-Vis spectroscopy.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914
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