Tomoaki Yuzuri

Intramolecular CH-? interaction. Substituent effect as a probe for hydrogen bond-like character

The contribution of a charge-transfer term to the CH–π interaction is supported by ab initio calculations and experiments on the substituent effect. NOE is an effective tool to determine the CH–π interacted folded conformers separately from the stretched conformer. Copyright

Electronic substituent effect on intramolecular CH/π interaction as evidenced by NOE experiments

In order to demonstrate the hydrogen-bond-like character of the CH/π interaction, electronic substituent effects on the equilibria between the stretched and the folded conformers of series of compounds capable of forming CH/π interactions were examined by measurements of NOE enhancements of 1H NMR signals. Nuclear Overhauser enhancement is shown to be useful to determine the abundance of the CH/π proximate folded conformer. The Hammett plots of all series of the compounds capable of having CH/π interaction gave negative ρ values. Together with other substituent effects (effects of electronegative substituents, on the CH donor, of ring size, and of α-alkyl substituent), the involvement of delocalization interaction and the hydrogen-bond-like character of the CH/π interaction were established.

Rotational Barriers and 15N Chemical Shifts of N‐Acyl‐N‐alkyl‐substituted Amino Acids

Rotational barriers about the C—N bonds of several N‐acyl‐N‐methyl‐α‐amino acids and their esters R3CO—N(R4)—CR1R2—COOR5, and also N‐Boc‐protected dipeptides, were determined and the steric effects caused by the substituents R1–R5 are discussed by comparing them with the results of MM3 calculations on these amides. Bulky substituents on both the acyl group and the nitrogen atom were shown to have lower ΔG‡. In the series of N‐acylglycines with variable R3, the 15N chemical shifts were correlated with ΔG‡.

CH/π Interaction on the Structure of N-Substituted-4-phenyltetrahydroisoquinoline Derivatives

Rotational barriers about the C–N bonds and differences of ground state energies of tert-butyl 4-phenyltetrahydroisoquinoline-2-carboxylate derivatives were determined by NMR spectroscopy. The resu...

Structure-Sweetness Relationships of Aspartame Derivatives by GUHA

Structure-Sweetness Relationships of Aspartame derivatives have been established using fingerprint descriptors by GUHA method. GUHA is the acronym for General Unary Hypotheses Automaton. The glucophoric hypotheses on the reasons for sweetness of aspartame derivatives were generated. Moreover, new results on sweetness receptor site topology have been found. The results were confirmed both by theoretical studies of other authors and chemical evidence. New knowledge obtained can be used for tailoring new aspartame analogous as artificial sweeteners.

Computer Aided Hypotheses Based Drug Discovery Using CATALYSTRTM and PC GUHA Software Systems

CATALYSTRTM [1] and PC-GUHA [2], [3] software systems have been used in computer aided hypotheses based drug discovery. They are based on quite different principles. CATALYSTRTM represents molecular simulation approach based on search for common structure parts of drug molecules responsible for the therapeutic activity (pharmacophores). CATALYSTRTM is distributed by Molecular Simulation, Inc. GUHA is acronym of General Unary Hypotheses Automaton. GUHA is academic software distributed by the Institute of Computer Science of the Academy of Sciences of Czech Republic where it is being developed since 1960s. GUHA differs from various statistical packages enabling to test hypotheses that one has formulated, by its explorative character; it automatically generates hypotheses from empirical data by means of computer proceduresCATALYSTRTM [1] and PC-GUHA [2], [3] software systems have been used in computer aided hypotheses based drug discovery. They are based on quite different principles. CATALYSTRTM represents molecular simulation approach based on search for common structure parts of drug molecules responsible for the therapeutic activity (pharmacophores). CATALYSTRTM is distributed by Molecular Simulation, Inc. GUHA is acronym of General Unary Hypotheses Automaton. GUHA is academic software distributed by the Institute of Computer Science of the Academy of Sciences of Czech Republic where it is being developed since 1960s. GUHA differs from various statistical packages enabling to test hypotheses that one has formulated, by its explorative character; it automatically generates hypotheses from empirical data by means of computer procedures