新型異斯特維醇衍生物的合成及其不對稱催化性能研究
發(fā)布時間：2019-02-13 15:28
【摘要】：本論文以天然產(chǎn)物甜菊糖苷衍生而來具有剛性骨架的貝葉烷型四環(huán)二萜類化合物異斯特維醇(Isosteviol)為先導(dǎo)化合物，通過酯化、羥甲基化、肟化、氧化、還原等反應(yīng)對其進行結(jié)構(gòu)修飾和改造，在其骨架上引入羥基、肟基、雜環(huán)、硫脲、以及α，β不飽和羰基等活性基團，共合成出27個新型異斯特維醇功能取代衍生物，其中16個是未見于文獻報道的新化合物。所得新化合物的結(jié)構(gòu)經(jīng)IR、1HNMR、13CNMR和HRMS表征�？疾炝肆u基硫脲類異斯特維醇衍生物作為小分子催化劑對不對稱Petasis反應(yīng)的催化活性和立體選擇性。合成了一系列異斯特維醇衍生的新型手性二齒配體，用UV-Vis光譜考察了其對不同金屬離子的配位性能，研究了手性配體存在下金屬離子對不對稱Henry反應(yīng)的催化性能。具體研究工作如下： 一、C環(huán)擴環(huán)異斯特維醇衍生物的合成 以甜菊糖苷為原料，在酸性條件下水解重排得到異斯特維醇，經(jīng)過酯化和羥甲基化反應(yīng)得到15α-羥甲基-16β-羥基異斯特維醇乙酯。然后經(jīng)對甲苯磺酰氯取代、堿性消除得到化合物6，在三氟化硼催化作用下與苯胺反應(yīng)得到重排擴環(huán)產(chǎn)物7，后者SeO2對烯丙位氧化得到含有羥基的苯胺取代的C環(huán)擴環(huán)衍生物8。 二、15-α-羥甲基16-α-取代硫脲基異斯特維醇衍生物的合成及其對不對稱Petasis反應(yīng)的催化性能研究 化合物6轉(zhuǎn)化成相應(yīng)醛肟10后，在三氟化硼催化下發(fā)生分子內(nèi)1，3-偶極加成生成惡唑烷衍生物11，后者在雷尼鎳催化下氫化開環(huán)得到15-α-羥甲基16-α-氨基異斯特維醇衍生物16�；衔�16與取代的異硫氰酸苯酯反應(yīng)得到9種15-α-羥甲基16-α-取代硫脲基異斯特維醇衍生物。考察了化合物15作為手性有機小分子催化劑對不對稱Petasis反應(yīng)的催化活性和立體選擇性。 三、15-α-羥甲基16-α-取代氨基異斯特維醇手性配體的合成及其金屬配位催化性能研究 15-α-羥甲基16-α-氨基異斯特維醇衍生物16與水楊醛或吡啶甲醛反應(yīng)得到相應(yīng)的亞胺25和27，25經(jīng)硼氫化鈉還原得到含有羥基、取代胺基的異斯特維醇衍生物26。用UV-Vis譜考察了各化合物分別與不同金屬離子的配位性能及其對不對稱Henry反應(yīng)中的催化活性和立體選擇性。
[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 偽, 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 偽 -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- 偽 -hydroxymethyl 16- 偽 -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- 偽 -hydroxymethyl 16- 偽 -aminoisosterol derivative 16- 偽 -hydroxymethyl 16- 偽 -aminoisosteryl alcohol under the catalytic hydrogenation of Raney nickel. Compound 16 reacted with substituted phenylethyl thiocyanate to obtain nine derivatives of 15- 偽 -hydroxymethyl 16- 偽 -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- 偽 -hydroxymethyl 16- 偽 -substituted aminoisostavitol and their catalytic properties for metal coordination; 15- 偽 -hydroxymethyl-16- 偽 -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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R914
本文編號：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 偽, 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 偽 -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- 偽 -hydroxymethyl 16- 偽 -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- 偽 -hydroxymethyl 16- 偽 -aminoisosterol derivative 16- 偽 -hydroxymethyl 16- 偽 -aminoisosteryl alcohol under the catalytic hydrogenation of Raney nickel. Compound 16 reacted with substituted phenylethyl thiocyanate to obtain nine derivatives of 15- 偽 -hydroxymethyl 16- 偽 -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- 偽 -hydroxymethyl 16- 偽 -substituted aminoisostavitol and their catalytic properties for metal coordination; 15- 偽 -hydroxymethyl-16- 偽 -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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R914
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相關(guān)期刊論文 前3條
1 閻學(xué)斌,雷萌,張建業(yè),劉宏民;冬凌草甲素葡萄糖苷的合成[J];有機化學(xué);2005年02期
2 高幼衡，萬振先，，賴學(xué)文，朱英，李廣義，吳順華;顯脈香茶菜化學(xué)成分的研究[J];中國中藥雜志;1994年05期
3 于濤;李慧;伍新燕;楊軍;;Petasis反應(yīng)研究進展[J];有機化學(xué);2012年10期
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