Host-Guest Complexation. 31. A Transacylase Partial Mimic

Article abstract of DOI:10.1021/ja00329a059

The first two stages are reported of an incremental approach to the synthesis of hosts that mimic serine transacylases.The hosts are 20-membered macrocycles and are composed by attaching to one another aryloxy, cyclic urea, pyridyl, biphenyl, ethylene, methylene and oxygen units.The structures and points of attachment of all but the latter two units are drawn and are symbolized by capital letters.The structures of the hosts and synthetic intermediates are indicated by line formulas consisting of sequences of letters, which represent sequences of units bonded to one another in the host. A, A', U, B, Py, D, Nap, E.In the first stage of our approach the compound U(A'UCH2)2A' was designed and prepared and its binding properties toward Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺, NH4⁺, CH3NH3⁺, and t-buNH3⁺ picrates in CDCl3 at 25 deg C were determined.The free energies of binding (-ΔGdeg values) varied from a low of 12.1 to a high of 15.2 kcal mol^-1.A crystal structure of the complex U(A'UCH2)2A'*t-BuNH3ClO4 indicated the substance possessed the expected organization.The complex is held together by the three hydrogen bonds RN⁺(H...O=C)3 in which the carbonyl groups are parts of the three cyclic urea units (U).The high binding power of U(A'UCH2)2A' is attributed the presence of the three cyclic urea units and particularly to their high degree of preorganization.The key ring-closing reaction involved H-U-A'-U-A'-U-H reacting with BrCH2-A'-CH2Br in tetrahydrofuran-NaH to produce U(A'UCH2)2A'*NaBr (50percent).In the second stage, host U(A'UCH2)2BCH2OH was designed and prepared by similar reaction between H-U-A'-U-A'-U-H with (Br(CH2)2BCH2OCH3 to produce U(A'UCH2)2BCH2OCH3 (36percent), which was converted to U(A'UCH2)2BCH2OH.This compound contains both a binding site complementary to RNH3⁺ guests and a nucleophilic hydroxyl group complementary to the guest carbonyl group in complexes such as U(A'UCH2)2BCH2OH*CH3CH(CO2C6H4NO2-p)NH3ClO4.The -ΔGdeg values of U(A'UCH2)2BCH2OH binding the above picrate salts series in CDCl3 at 25 deg C varied from a low of 10.6 to a high of 15.4 kcal mol^-1.When the alanine complex of this nucleophilic host was dissolved in CH2Cl2-10percent pyridine (by volume) at 25 deg C, transacylation occurred to give U(A'UCH2)2BCH2O2CCh(CH3)NH3ClO4.The kinetics of transacylation were followed in CDCl3 buffered with R3N-R3NHCLO4 (R3N is diisopropylethylamine).Pseudo-first-order (saturation) kinetics were observed under conditions where host concentration greatly exceeded that of guest.The reaction was first order in buffer ratio, and therefore the active nucleophile O^-.Under the same reaction conditions, the noncomplexing model compound, H2BCH2OH, underwent no detectable reaction.Upper limits were placed on its rate of acylation.Comparisons of the bimolecular acylation rates by CH3CH(CO2C6H4NO2-p)NH3ClO4 of U(A'UCH2)2BCH2OH and of H2BCH2OH were made to assess all the effects of comlexing.The complexing system has a second-order rate constant that is ca 10¹¹ times greater than the second-order rate constant ...