【作者】 王琼；

【导师】 盛寿日；

【作者基本信息】 江西师范大学 ， 高分子化学与物理， 2007， 硕士

【摘要】 本文研究了聚乙二醇负载α-苯硒基羧酸酯试剂的制备及其在液相有机合成中的应用。1、在4-二甲胺基吡啶(DMAP)和N, N’-二环己基碳二亚胺(DCC)存在下,二羟基聚乙二醇(PEG) 4000与α-苯硒基丙酸于二氯甲烷中反应制得PEG负载α-苯硒基丙酸酯试剂。该试剂经N, N-二异丙胺基锂(LDA)作用后与醛反应,再经30 %的双氧水氧化脱硒,形成PEG负载Baylis-Hillman产物中间体,最后用0.1 N甲醇钠/甲醇或氢氧化钠溶液将目标产物从树脂上切割下来,以较好产率和较高纯度制得相应的Baylis-Hillman产物。该法具有反应条件温和、操作简单、分离方便、产率好(80-94 %)、纯度高(>92 %)等优点。2、以PEG负载α-苯硒基丙酸酯试剂和醛为起始原料,按上述方法制得PEG负载的B-H产物。将此中间体与芳基亚磺酸钠在无水MeOH/DMF (V / V, 3/1)混合溶剂中并于80 oC反应,制得相应的PEG负载三取代乙烯——2-芳基磺酰甲基-2-烯羧酸酯中间体,继而用0.1 N甲醇钠/甲醇溶液作为PEG的切割试剂,以较好产率(75-91 %)和纯度(91-95 %),立体选择性合成了(2Z)-2-芳基磺酰甲基-2-烯羧酸甲酯。3、按前法以PEG分别和α-苯硒基乙酸、α-苯硒基苯乙酸反应制得PEG负载α-苯硒基乙酸酯、PEG负载α-苯硒基苯乙酸酯试剂。将此试剂用N, N-二异丙胺基锂(LDA)作用后与环氧化合物反应,再经30 %的双氧水氧化脱硒,形成PEG负载γ-羟基-α,β-不饱和羧酸酯,最后在对甲苯磺酸促进下,用甲苯为溶剂,加热回流反应,以优良产率(80-85 %)得到5-(或3, 5-)取代-α,β-不饱和丁内酯。该法对含α,β-丁烯酸内酯结构的天然产物分子库的建立以及在药物筛选中均有潜在的应用。更多还原

【Abstract】 In this dissertation, the preparation of poly(ethylene glycol) supportedα-phenylseleno carboxylic acid ester reagents and their applications in liquid-phase organic synthesis reaction were investigated.Firstly, Reaction of difunctional PEG 4000 withα-phenylselenopropanoic acid in anhydrous dichloromethane in the presence of DCC/DMAP readily gave rise to PEG-boundα-phenylselenopropionate ester, which was reacted with LDA, followed successively by treatment with aldehyde and 30 % hydrogen peroxide afforded PEG-bound Baylis-Hillman product intermesiate, and subsequent cleavage from the PEG using 0.1 N MeONa in methanol or sodium hydroxide aqueous solution afford Baylis-Hillman product with good yields (80-94 %) and high purities (>92 % by HPLC analysis) of the crude products.Secondly, Treatment of PEG-supported Baylis-Hillman products, which were prepared from PEG-supportedα-phenylselenopropionate with aldehydes, with sodium arylsulfinate in anhydrous MeOH/DMF (V/V, 3/1) mixture solvents at 80 oC afforded the corresponding PEG-supported trisubstituted ethylene——2-arylsulfonyl- methyl-2-alkenoate intermediates. The resulting PEG-bound sulfonylated products were cleaved from the PEG efficiently using 0.1 N MeONa in methanol affording methyl (2Z)-2-arylsulfonylmethyl-2-alkenoates stereoselectively in good yields (75-91 %) and high purities (91-95 % by HPLC analysis).Finally, PEG-supportedα-phenylselenoacetate and PEG-supportedα-phenylselenophenylacetate esters were prepared from PEG 4000 withα-phenylselenoacetic acid andα-phenylselenophenylacetic acid in similar methods as above, respectively. Treatment of these PEG-supportedα-phenylselenocarboxylic acid esters with LDA, followed successively by treatment with epoxide and 30 % hydrogen peroxide afforded PEG-boundγ-hydroxy-α,β-unsaturatecarboxylic acid ester intermesiates, and subsequent cleavage from the PEG using p-toluenesulfonic acid monohydrate in toluene at refluxing temperature afford substituted (5- and 3,5-di) α,β-butenolides with good yields (80-94 %). The described technology and sequence has potential application in combinatorial synthesis of butenolide-containing natural product libraries for chemical biological screening and the drug discovery process.更多还原