【作者】 徐汶；

【导师】 刘宏民；

【作者基本信息】 郑州大学 ， 有机化学， 2002， 博士

【摘要】 本文通过研究2-位氧化α-甲基D-葡萄糖苷在合成方法学中的应用，开发出了合成2-脱氧氨基糖苷和分枝糖苷的新方法。其中在2-位氧化α-甲基D-葡萄糖苷的芳胺亲核加成反应中发现了三个新的氨基糖合成方法，并利用其中的两个合成了两个系列共十七种新型的2-脱氧2-芳胺基3-位氧化α-甲基D-葡萄糖苷类和含糖吲哚类衍生物，进而对其中的十一种3-位氧化糖类衍生物进行立体专一性还原合成了一系列阿洛糖胺类衍生物；以硝基甲烷与2-位氧化α-甲基D-葡萄糖苷的立体选择性HenrY反应为基础，合成了重要的2-脱氧2-硝甲基α-甲基D-葡萄糖苷分枝糖。取得的主要成果如下： 一、发现了2-位氧化α-甲基D-葡萄糖苷的芳胺亲核加成引起羰基转位的新方法，利用核磁共振氢谱及碳谱对邻苯二胺与2-位氧化α-甲基D-葡萄糖苷加成生成的稳定中间体半缩酮化合物在氘代丙酮中的的变化进行跟踪，结合对转化产物的氢氢相关谱和HMQC结构确证，提出了该反应中2-位羰基通过烯醇化互变而转至3-位的机理并得到了验证。选择不同类型的芳胺利用该反应合成了一系列共十三种2-脱氧2-芳胺基3-位氧化α-甲基D-葡萄糖苷(5～17)，该类化合物为重要的手性合成子。并利用利用两种邻苯二胺与2-位氧化α-甲基D-葡萄糖苷反应合成了两种含糖吡嗪衍生物。 二、在2-位氧化α-甲基D-葡萄糖苷与芳胺的亲核加成反应中发现了另外两个新方法：1)芳胺亲核加成引起羰基转位伴随脱除1-位甲氧基的反应，利用该反应合成了两种不饱和氧化糖类衍生物；2)双分子强亲核性芳胺与2-位氧化α-甲基D-葡萄糖苷加成生成含糖吲哚类衍生物的反应，提出了首先单分子芳胺加成引起 摘 要毅基转位伴随甲氧基脱除，然后第二分子芳胺加成伴随分子内亲电取代的反应机理，并利用该反应合成了一系列共四种含糖吼跺类新结构化合物c X从而将2．位氧化a－甲基卜葡萄糖昔应用于生物碱类化合物的合成之中。 NH、厂＼f3 D－P卜一、／一cD 。。O＿RZ、xzx ＼n－－J Y xw－R。 P卜 一一o’”“x－y＼o一＼hwr vxx’”’ PO、＋11I”r＝x 111 ． w ／w EtOH．6hreflux八N r O人，u＼广“R，HH 汀＼尸 一＊c比【n3 卜 口1 R。Kg＼．Wx P。 RI 300poO。d 20：RI＝OCH3，民＝R3＝H ZOOp000d 2！：RI二CH3，RZ＝R3＝H 300p000d22：Rl＝RZ＝CH3 RHH comPOund 23：RI＝H，民＝民＝CH3 三、利用2－位氧化Q－甲基D－葡萄糖昔加成合成出的2．脱氧2．芳胺基3。位氧化a－甲基D－葡萄糖昔类化合物中的3－位碳基所处的强烈手性环境，对其进行了立体专一性的NaBH。还原，进而合成了一系列共十一种新型阿洛糖胺衍生物p6～46卜并对反应的立体化学问题进行了讨论，认为该反应的立体专一性是由于向下直立键上的卜位a－甲氧基和2－位向下平伏键上芳胺基大基团的共同影响，造成内侧进攻受阻，而使得氢负离子只能从外侧进攻的结果。所得2－脱氧2－芳胺基a－甲基D－阿洛糖昔化合物构型经X－射线单晶衍射图证实确为3－位羟基处于向下直立键。该反应为合成稀有的阿洛糖胺类化合物提供了新的途径，该方法以资源丰富的D－葡萄糖为原料，选择性高，较之已有报道的合成方法更为经济有效，所合成的阿洛糖胺类衍生物由于氨基取代基富于变化，而可用于新型几丁酶抑制剂的筛选。 Ph一＼一O一＼＿＼＿ O一ywv＼ liN。RH。HO一HA N ＼；，b 2） 40％AcOH Mth ”IOCH。OH OCH3 RR R＝H（36）；P－OCH3 （37；O－CH3（38）；m－CH3（39）；PCH3（40）； 2，4－Dimethyl（4！）；2，5－Dimethyl（42）；。－CI（43）；pCI（44）； P－刀（45）： P－Br（46） 四、采用Yoshikawa的方法，以2－位氧化a－甲基D－葡萄糖昔为原料，立体选择性地合成了2－脱氧上1 甲基分枝糖60卜对于其中涉及到的两个立体化学问题2 摘 要选择性地合成了2－脱氧工巧甲基分枝糖O0卜对于其中涉及到的两个立体化学问题进行了分析：通过He啊反应产物的X－射线单晶衍射图证实了其构型，澄清了该反应在常温下以热力学控制产物为主，硝甲基从2－位碳基内侧进攻而处于向?更多还原

【Abstract】 In this thesis, using of methyl 2-keto a-D-glucopyranoside in synthetic methodology was discussed. Through studying on the nucleophilc addition of anilines to methyl 2-keto a-D-glucopyranoside and the Henry reaction, some new methods have been developed to prepare 2-deoxy amino glycosides and branched-chain monosaccharides. Among the three novel reactions found in the research on anilines’ addition to methyl 2-keto a-D-glucopyranoside, two ones were used for synthesis of two kinds of totally seventeen new compounds, including 2-arylamino-2-deoxy 3-keto glucopyranosides and indole derivatives with sugar unit. Then eleven D-allosamine derivatives were obtained by stereo-specific reduction of the 3-keto glycosides. Furthermore, based on the stereo-selective Henry reaction of methyl 2-keto a-D-glucopyranoside, methyl 2-nitromethyl-2-deoxy a-D-glucopyranoside which is an important branched sugar was prepared. The mail results obtained are as follows.1. A novel carbonyl transposition led by anilines’ nucleophilic addition to methyl 2-keto a-D-glucopyranoside was discovered. And the mechanism of the reaction concerned to an enol rearrangment was provided through tracing the change of ’H-NMR and I3C-NMR of a hemiacetal intermediate which was obtained in the reaction of o-phenylene diamine with 2-keto glycoside. Both the intermediate and the converting product were identified by ’H-NMR, 13C-NMR, !H-’H COSY and HMQC. Making use of this reaction, thirteen methyl 2-arylamino-2-deoxy 3-keto glucopyranosides (5~17) with different substituted arylamino groups and twoR= p-OCH3(5), H(6), o-CH3(7), m-CH3(8),p-CH3 (9), 2, 4-Dimethyl (10), 2, 5-Dimethyl(Il), p-OH (12), o-CI (13), p-CI(14), p-F(15), p-Br(16), p-COOEt(17)pyrazine derivatives have been synthesized. And the 3-keto glycosides can be employed to asymmetric synthesis.2. Two other new reactions were found in studying the anilines’ nucleophilic addition to methyl 2-keto cc-D-glucopyranoside. One was the carbonyl transpostional reaction accompanied with the demethoxyl process which happened when 2-keto glucoside interacted with benzocaine and 2,4-dichlor aniline. Two oxo glucals were obtained by this method. The other was the one-step reaction for the synthesis of indole derivatives containing sugar unit was achieved by two equivalents of strong nucleophic anilines" addition to 2-keto glucoside. The possible mechanism was provided as following. At first, one molecular aniline attacked to the 2-keto group leading to the transposition of carbonyl associated with demethoxyl reaction. Then the second molecular of aniline attacked the 3-keto group accompanied with intramolecular electrophilic substitution. Using this reaction, four indole derivatives (20~23) have been prepared. This reaction provides a method to synthesis of alkaloid from 2-keto glycoside.3. The stereospecific reduction of methyl 2-arylamino-2-deoxy 3-keto glucopyranoside has been also studied. When the 3-keto glycosides was reduced by sodium borohydride, the D-allo configuration was considered the most probable since it has an equatorial arylamino group at C-2 position and reduction of the keto group was considerably less hindered to equatorial attack by borohydride ion to give an axial hydroxyl, than axial attack by borohydride to give an equatorial hydroxyl. Eleven methyl 2-arylamino-2-deoxy a-D-allopyransides (36~46) were obtained as expected. And the configuration of the product was elucidated by the X-ray diffraction analysis. This reaction provides a new way to synthesis of D-allosamine?derivatives which is the candidate of new type of chitinase inhibitor. In consideration of that the substrate we used was the most abundant hexose, D-glucose, this synthesis was more convenient to the others reported.R = H (36); p-OCH3 (37); O-CH3 (38); m-CH3 (39); p-CH3 (40); 2,4-Dimethyl (41); 2,5-Dimethyl (42); o-Cl (43); p-Cl (44); p-F(45); p-Br(46)4. Methyl 2-nitromethyl-2-deoxy a-D-glucopyranoside (50) was stereo-selective synthesized by Yo更多还原