Cyclodextrin-Mediated Deacylation of Amino Acid Esters with Marked Stereoselectivity.

Abstract

Stereoselective hydrolysis of amino acid esters have attracted considerable attention in connection with understanding the origins of the stereoselectivity observed with proteolytic enzymes. In the course of our study on the enantioselective hydrolysis (deacylation) of amino acid esters with the functional molecular assemblies composed of surfactants and reactive species, we emphasized that the stereochemical control could be attained by changing the composition of the coaggregates 1-4) and regulating ionic strength 5,6) and temperature. 7,8) Furthermore, since cyclodextrins (CyDs) have been noted as useful enzyme mimics, 9-12) we employed CyDs as host molecules and a markedly high stereoselectivity was attained in the diastereoselective deacylation of dipeptide esters.13) On the other hand, Ueno reported the high D-enantiomer-selective deacylation of amino acid esters mediated by modified b-CyDs.14) However, little has been known about the significant enantioselectivity for the deacylation of amino acid esters with unmodified CyDs. 15) In this study, we report the successful experimental results with marked enantioselectivity for the deacylation of Z-D(L)-amino acid esters (N-(benzyloxycarbonyl)-D(L)-amino acid pnitrophenyl esters) as mediated by unmodified CyDs, and the computer modeling (molecular mechanics) studies on the inclusion complexes of g-CyD with the specific substrates are also presented. Results and DiscussionWith respect to the enantioselective hydrolysis (deacyla-Leu, Phe and Trp-PNP) mediated by unmodified a-, b-and g-CyDs, the kinetic parameters obtained on the basis of the MichaelisMenten principle, the binding constant (K b ) for the formation of CyD-substrate complex and the rate constant (k 2 ) for the deacylation of substrate by CyD, are summarized in Table 1-3. The noteworthy aspects are as follows: (a) Overall, the deacylation mediated by a-CyD was favorable for all of the L-enantiomeric substrates (reflected in k 2 K b , L/Dϭ1.5-1.7), though the K b for D-isomer of Phe substrate and k 2 values for D-isomer of Ala substrate were larger than those for the corresponding L-isomers. (b) In the case of the reaction by bCyD, L-enantiomer-selectivity was also observed for the deacylation of Ala, Leu and Phe substrates (L/Dϭ1.5-3.2), while D-enantiomeric selectivity (D/Lϭ1.4) was observed for the deacylation of Trp substrate. (c) Relatively higher L-enantioselectivity was obtained in the deacylation mediated by gCyD (L/Dϭ2.6-9.0). Most remarkably, the highest enantioselectivity (L/Dϭ9.0) was attained for the deacylation of Ala substrate. Furthermore, it was also attractive that this fairly high enantioselectivity (L/Dϭ9.0) could be mainly originated in the deacylation process of substrates, because it was reflected by a fairly large k 2 L /k 2 D value (7.4) and a smallOn the other hand, Table 4 shows the results of energies for the inclusion complexes on Z-D(L)-Ala-PNP having different shapes with g-CyD calculated by molecular mechanics with water solvent effects. It was suggested that the con...

The angular momentum controversy: What’s it all about and does it matter?

“…Moreover, the same idea reappeared in the works of e.g. Goto [84], Treat [85,86], Duan [87][88][89][90], Fulp [91], and Kashiwa and Tanimura [92,93]. However, since Chen et al revived this idea in the context of the controversy about the angular momentum decomposition, we shall refer to the generic split (167) as the "Chen et al approach".…”

Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

“…CDs play an important role in preorganizing the guest molecules through the hydrophobic interactions. A number of studies have reported the use of unmodified or simply modified CD monomers without metal ions for the enantioselective deacylation of chiral esters 26 27 28 29 30 31 32 . However, the cooperative enantioselective catalytic effect arising from CDs’ intramolecular interactions with coordinated metal ions have rarely been reported, and the cooperative mechanism also remains unclear.…”

Enantioselective hydrolysis of amino acid esters by non-chiral copper complexes equipped with bis (β-cyclodextrin)s

“…The value was among the largest ones which were gained by using CD-based [29][30][31] or other surfactants containing complex [49,50] as artificial mimics, and are close to those cases by using enzymes or modified enzymes [5,47,50,51], for the hydrolysis of amino acid esters or peptide esters. The hydrolysis of Boc-Lys(Boc)-ONp enantiomers promoted by CuL 1 resulted in more pronounced enantioselectivity than that of Boc-Ala-ONp, with an enantiomer selectivity of 8.8.…”

“…Fig. 2 shows the dependence of the rate constants on the CuL 1 concentration [28,29,[47][48][49]. By increasing the initial catalyst concentration from 5.0 to 100.0 M, deviation from linear increase was observed (Fig.…”

“…CDs play an important role in preorganizing substrates by means of the noncovalent interactions brought by the hydrophobic chiral cavities. Ueoka [28,29], Ueno [30,31], and others [32][33][34][35] reported the deacylation of amino acid or dipeptide esters with high enantioselectivity, catalyzed by unmodified CDs or functional group-containing CD monomers. However, few study focused on the cooperation between the metal cofactor and the second coordination sphere effect for enantioselective deacylation of amino acid esters [36].…”