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Fine Regulation of Guest-Orientation Based on Asymmetry of Host Cavity and Their Application to Construction of Active Artificial Enzymes

基于宿主腔不对称性的客体取向精细调控及其在活性人工酶构建中的应用

基本信息

批准号：
14350478
负责人：
FUJTTA Kahee
金额：
$ 9.47万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Many artificial enzymes have been constructed through functionalization of cyclodextrins(CDs) whose cavities afford substrate (guest)-binding sites. However, since the substrates are allowed to rotate in the CD cavities along their Cn symmetry axes, the substrates react only accidentally with the functional groups attached on the CD rims during the tour inside the cavities. In this context, it is of great challenge to prepare artificial receptors capable of restricting substrate-orientation and then to functionalize them by introducing the desired number of desired functionalities into the desired positions.We prepared mono- or di-altro-β-CDs from β-CD by converting one or regioselectively two glucosides unit to altrosides and demonstrated that they form the elliptically distorted cavity and possess very unique molecular recognition properties. That is, upon binding a flat guest, they become more elliptical to better fit the geometry of guest and to restrict the guest orientation. Howe … More ver, they contain no functionality other than OH groups and demonstrate only confined binding strength. Improvement of its binding ability and introduction of additional functionality depend undoubtedly on the methodological discovery of appropriate modification. We clarified that the elliptical cavity of mono-altro-β-CD could restrict the orientation of a guest-type sulfonylating reactant, 1-naphthalensulfonyl chloride(1-NsCl) and direct the sulfonyl group to the 2^A-OH of the altroside residue and 3^G-OH of the glucoside residue to afford regioselectively the 2^A-O-sulfonate and 3^G-O-surfonate. The latter compound was converted to with 2^G,3^G-alloepoxy-mono-altro-β-CD promising of regioselective functionalization of G residue adjacent to the unmodified altroside resiue A.From the sulfonylation reaction of A,X-di-altro-β-CD (X=B-D) with 2-NsCl in aq. CH_3CN,2^A-mono-sulfonates and 2^D-mono-sulfonate were selectively prepared as the major products in the former two cases and the last one, respectively. The result implies that A,X-di-altro-β-CD is capable of restricting the orientation of the guest 2-NsCl and the cavity shape may be mainly governed by one altrose residue. The surfonates are easily convertible to the corresponding 2,3-alloepoxides which may readily react with appropriate nucleophiles to give functionalized mono- and di-altro-β-CDs that have desired functional groups on the specific positions and the distorted cavities to restrict the orientation of substrates.The 2^A-SH substituent (3) of 3,6-anhydro-β-CD was prepared from 2^A,3^A-alloepithio-β-CD which we prepared by stereoinversion reaction of 2^A,3^A-mannoepoxy-β-CD as well as the 2^A-SH substituent (1) or the 3^A-SH one (2) from 2^A,3^A-manno- or allo-epoxy-β-CD, respectively. The pka of the SH groups of 1,2,and 3(7.8,8.2,and 9.6,respectively) were considerably small as compared to the normal value (pKa 11-12), suggesting their esterase activity under the neutral aqueous conditions. Actually, they hydrolyzed m-nitrophenyl (or p-nitrophenyl) acetate 860(1700), 150(170), and 2300(170) times faster than the non-catalyzed reactions in the neutral buffer solution (pH 9.0,25℃) where the catalysis of β-CD was negligible. Less

许多人工酶是通过环糊精（CD）的功能化来构建的，环糊精的空腔提供了底物（客体）结合位点。然而，由于允许基底在CD腔中沿着它们的Cn对称轴旋转，因此在腔内部的巡回期间，基底仅偶然地与连接在CD边缘上的官能团反应。在这一背景下，制备能够限制底物取向的人工受体，然后通过将所需数量的所需官能团引入所需位置来使其功能化，这是一个巨大的挑战。CD通过将一个或两个糖苷单元区域选择性地转化为阿卓糖苷，并证明它们形成椭圆形扭曲空腔，具有非常独特的分子识别能力特性.也就是说，在结合平坦客体时，它们变得更椭圆以更好地配合客体的几何形状并限制客体取向。豪 ...更多信息相反，它们不含除OH基团以外的官能团，并且仅表现出有限的结合强度。其结合能力的提高和附加功能的引入无疑取决于方法学上发现适当的修饰。说明单阿洛-β-CD的椭圆形空腔可以限制客体型磺酰化反应物1-萘磺酰氯（1-NsCl）的取向，并将磺酰基团引导到阿卓糖苷残基的2^A-OH和葡萄糖苷残基的3^G-OH上，从而区域选择性地得到2^A-O-磺酸酯和3^G-O-磺酸酯。后者化合物被转化为2^G，3^G-别环氧-单-altro-β-CD，有望区域选择性官能化邻近未修饰的阿卓苷残基A的G残基。根据A，X-二-altro-β-CD（X=B）与2-NsCl水溶液的磺酰化反应。在前两种情况和后一种情况下，主要产物分别是CH_3CN、2^A-单磺酸盐和2^D-单磺酸盐。结果表明，A，X-di-altro-β-CD能够限制客体2-NsCl的取向，空腔形状可能主要由一个阿卓糖残基控制。磺酸盐很容易转化为相应的2，3-别环氧化物，这些环氧化物可以很容易地与适当的亲核试剂反应，得到官能化的单-和二-altro-β-CD，这些CD在特定位置上具有所需的官能团和扭曲的空腔，以限制底物的取向。3，6-脱水-β-CD的2^A-SH取代基（3）是从2^A，3^A-别环硫基-β-CD是由2 ^A，3^A-甘露环氧-β-CD和2 ^A，3 ^A-甘露环氧-β-CD分别经立体转化反应得到的2^A-SH取代基（1）或3^A-SH酮（2）。SH基团1、2和3的pKa值（分别为7.8、8.2和9.6）比正常值（pKa 11- 1,2）小得多，表明它们在中性水溶液中具有酯酶活性。在中性缓冲溶液（pH9.0，25 ℃）中，β-CD的催化作用可以忽略，它们水解间（或对）硝基苯乙酸酯的速度分别是非催化反应的860（1700）、150（170）和2300（170）倍。少