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

许多人工酶是通过环糊精（CDs）的功能化而构建的，其空腔提供底物（客体）结合位点。然而，由于允许底物在CD腔内沿其Cn对称轴旋转，因此底物在腔内巡回时仅与附着在CD边缘上的官能团偶然发生反应。在这种情况下，制备能够限制底物取向的人工受体，然后通过在所需位置引入所需数量的所需功能来使其功能化是一项巨大的挑战。我们将β-CD中的一个或两个糖苷单元选择性地转化为醛苷，制备了单或双醛苷-β-CD，并证明了它们形成椭圆畸变腔，具有非常独特的分子识别特性。也就是说，在绑定平面来宾后，它们变得更加椭圆，以更好地适应来宾的几何形状，并限制来宾的方向。更重要的是，它们除了OH基团外不含任何功能，并且仅表现出有限的结合强度。其绑定能力的改进和附加功能的引入无疑依赖于对适当修改的方法学发现。研究结果表明，单α -β-CD的椭圆腔可以限制客体型磺化反应物1-萘磺酰氯（1-NsCl）的取向，并将磺酰基定向到α -糖苷残基的2^ a - oh和3^G-OH上，从而选择性地提供2^ a - o-磺酸盐和3^ g - o-磺酸盐。后一种化合物与2^G，3^G-异氧基-单羟基-β-CD进行转化，在未修饰的altroside树脂A附近的G残基有区域选择性功能化的希望。在aq. CH_3CN中，A与2- nscl进行磺化反应，分别选择性地制备了2^A-单磺酸盐和2^ d -单磺酸盐。结果表明，A， x - 2- altro-β-CD能够限制客体2-NsCl的取向，并且空腔形状可能主要由一个altrose残基控制。这些表面酸盐很容易转化为相应的2,3-异氧环氧化物，这些异氧环氧化物可以很容易地与适当的亲核试剂反应，得到功能化的单羟基和双羟基β- cds，它们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。以2^A、3^A-甘露环氧树脂-β- cd和2^A- sh取代基(1)或3^A- sh取代基(2)为原料，分别用2^A、3^A-甘露环氧树脂-β- cd立体转化法制备了3,6-无羟基β- cd的2^A- sh取代基(3)。SH 1、2和3组的pka（分别为7.8、8.2和9.6）与正常值（pka 11-12）相比明显小，表明它们在中性水条件下具有酯酶活性。实际上，在中性缓冲溶液（pH 9.0,25℃）中，β-CD的催化作用可以忽略不计，它们水解间硝基苯基（或对硝基苯基）醋酸酯的速度比非催化反应快860（1700）、150（170）和2300（170）倍。少

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