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

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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