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About 97% of Escherichia coli strains produce beta-glucuronidase, but almost all other Enterobacteriaceae lack this enzyme. A D-glucopyranosiduronic acid (glucuronide) possessing a readily detectable beta-linked aglycone should, therefore, constitute a specific reagent for the detection of this organism. For this purpose, the title compound has been synthesized for the first time. The synthesis proceeds in eight steps from readily available D-glucuronolactone, anthranilic acid, and chloroacetic acid and can be carried out on a large scale. The compound has the predicted properties: when included in the standard membrane filter test for the analysis of water, indoxyl-beta-D-glucuronide allows specific detection of E. coli through the formation of blue colonies that are the result of rapid conversion of the liberated aglycone to indigo. The recovery of E. coli is easily measured and almost quantitative.

. Can. J . Chem. 65, 1845Chem. 65, (1987. The apparent twofold barriers to rotation about the exocyclic C-C bonds in ArCH2X (X = SH, SMe, S(O)Me, S02Me) compounds have been determined in CS, and in benzene-d6, from the magnitudes of long-range proton-proton coupling constants. The work extends earlier studies of the systems X = F, C1. Except for X = F, all of the title compounds have a low energy conformation in which the C-X bond is perpendicular to the plane of the benzene ring. The introduction of two meta-chlorine substituents leads to a 2 kJ/mol relative destabilization of this structure for X = F, C1, SH. The trend in the rotational barriers associated with the sulfur substituents is SH, SMe < < S(O)Me, S02Me. Ab initio calculations, with geometry optimization at the STO-3G level for X = F, C1, SH, reproduce the experimental results, and also the magnitudes of the rotational barriers. Quantitative PMO analyses of these a b initio wavefunctions have been employed to distinguish between "steric" and "other" interpretations, and reveal that the preferred conformation of X = F is determined by a first order perturbational effect, manifested in an electrostatic attraction between the heteroatom and a syn-periplanar ortho-hydrogen. For X = C1, the PMO analysis suggests that a T T~, -u & interaction, analogous to the n -~:~ interaction postulated as the origin of the anomeric effect in heterocyclohexanes, plays a dominant role. For X = SH, both T T~~-~:~ and ucx-n:, interactions are found; the latter is not possible in the anomeric effect itself. It is concluded that a benzylic anomeric effect exists, and that its magnitude, as a function Chem. 65, 1845Chem. 65, (1987.Utilisant les amplitudes des constantes de couplage proton-proton i longue distance, on a dCterminC les barrikres binaires apparentes 21 la rotation autour des liaisons exocycliques C-C des composCs ArCH2X (X = SH, SMe, S(0)Me et S0,Me) dans le CS2 et dans le benzene-d6. Ces Ctudes sont une extension d'etudes anttrieures sur des systkmes dans lesquels X = F et C1. Except6 pour le cas oB X = F, tous les composCs mentionnCs dans le titre prtsentent une conformation de basse Cnergie dans laquelle la liaison C-X est perpendiculaire au plan du noyau benzCnique. L'introduction de deux chlores en positions me'ta conduit a une distabilisation relative de 2 kJ/mol de cette structure pour X = F, C1 et SH. Cette tendance dans les barrikres rotationnelles associCes avec les substituants contenant du soufre est la suivante : SH. SMe << S(O)Me, S02Me. Des calculs a b initio impliquant des optimisations de la gComCtrie au niveau STO-3G ont CtC rCalisCs sur les composCs contenant X = F, C1 et SH et ils permettent de reproduire les resultats expkrimentaux ainsi que les amplitudes des barrikres a la rotation. On a utilisC des analyses quantitatives PMO de ces fonctions d'onde a b initio pour distinguer entre les interpretations ste'riques et antres; ces analyses rCvklent que la conformation privilCgiCe pour X = F est dCterminCe par un effet de perturbation du pre...

. Can. J. Chem. 66, 2733Chem. 66, (1988. Using the MMPEN parameters of Allinger's MMP2(85) force field, a conformational analysis has been performed on four biologically active penicillins: D-ampicillin, L-a-phenoxyethylpenicillin, penicillin G, and penicillin V, and on five biologically inactive or much less active penicillins: L-ampicillin, D-a-phenoxyethylpenicillin, N-methylpenicillin G, 6a-methylpenicillin G, and bisnorpenicillin G. Antibacterial activity is found to be associated with the existence of a global minimum having a compact structure, whose convex face is accessible to a penicillin binding protein (PBP), with the C3-carboxyl group and the side-chain N-H exposed on this face. Using the MMPEP parameters of MMP2(85), a conformational analysis has been performed on phenylacetyl-D-Ala-D-Ala-0-, a peptide model of the normal substrate of a PBP. Labischinski's global minimum has been reproduced, along with structures that correspond to Tipper and Strominger's proposal that the N4-C7 bond of a penicillin corresponds to the Ala-Ala peptide bond, and to Hasan's proposal that the N4-C5 bond of penicillin corresponds to the peptide bond. For both models, conformations of the peptide related to the pseudoaxial and pseudoequatorial conformations of the thiazolidine ring of penicillin G have been examined. It is concluded that penicillin is not a structural analog of the global minimum of the peptide; however, comparisons based on unbound conformations of PBP substrates are unable to determine which model is more appropriate, or which conformation of penicillin G is the biologically significant one. Using the ECEPPIMMPEP strategy, a model of the active site of a PBP has been obtained, following a search of 200,000 structures of the peptide Ac-NH-Val-Gly-Ser-Val-Thr-Lys-NH-Me. This peptide contains the sequence at the active site of a PBP of Streptomyces R61, for which it is also known that the C3-carboxyl group of penicillin binds to the €-amino group of lysine, and the p-lactam reacts chemically with the serine OH. The lysine and serine side chains and the C-terminal carbonyl group are found to occupy the concave face of the active site model.A strategy for the docking of penicillins or peptides to this model, with full minimization of the conformational energies of the complexes, has been devised. All active penicillins bind through strong hydrogen bonds to the C3-carboxyl group and the side-chain N-H, and with a four-centered relationship between the O-H of serine and the (0)C-N of the p-lactam ring. The geometrical parameters of this relationship are reminiscent of those found in the gasphase transition state of neutral hydration of a carbonyl group. When the energies of formation and geometries of the pseudoaxial and pseudoequatorial penicillin G complexes areexamined, there is now a clear preference forthe binding of the pseudoarial conformation, which is the global minimum of the uncomplexed penicillin in this case. A similar examination of the peptide complexes reveals that only the conformation of t...