Hiroko Satoh

Theoretical Investigation of Solvent Effects on Glycosylation Reactions: Stereoselectivity Controlled by Preferential Conformations of the Intermediate Oxacarbenium-Counterion Complex.

The mechanism of solvent effects on the stereoselectivity of glycosylation reactions is investigated using quantum-mechanical (QM) calculations and molecular dynamics (MD) simulations, considering a methyl-protected glucopyranoside triflate as a glycosyl donor equivalent and the solvents acetonitrile, ether, dioxane, or toluene, as well as gas-phase conditions (vacuum). The QM calculations on oxacarbenium-solvent complexes do not provide support to the usual solvent-coordination hypothesis, suggesting that an experimentally observed β-selectivity (α-selectivity) is caused by the preferential coordination of a solvent molecule to the reactive cation on the α-side (β-side) of the anomeric carbon. Instead, explicit-solvent MD simulations of the oxacarbenium-counterion (triflate ion) complex (along with corresponding QM calculations) are compatible with an alternative mechanism, termed here the conformer and counterion distribution hypothesis. This new hypothesis suggests that the stereoselectivity is dictated by two interrelated conformational properties of the reactive complex, namely, (1) the conformational preferences of the oxacarbenium pyranose ring, modulating the steric crowding and exposure of the anomeric carbon toward the α or β face, and (2) the preferential coordination of the counterion to the oxacarbenium cation on one side of the anomeric carbon, hindering a nucleophilic attack from this side. For example, in acetonitrile, the calculations suggest a dominant B2,5 ring conformation of the cation with preferential coordination of the counterion on the α side, both factors leading to the experimentally observed β selectivity. Conversely, in dioxane, they suggest a dominant (4)H3 ring conformation with preferential counterion coordination on the β side, both factors leading to the experimentally observed α selectivity.

Design of chemical glycosyl donors: does changing ring conformation influence selectivity/reactivity?

This tutorial review focuses on the design of glycosyl donors, especially on attempts to control selectivity/reactivity by employing bulky substituents, cyclic protecting groups, or bridged structures. These structural modifications are performed to change the conformational distributions of pyranoside/furanoside rings. We also briefly discuss this issue with regard to studies on furanosides and enzymatic glycosylation reactions. Readers will find that some of the designed glycosyl donors have been used to achieve total syntheses of natural products.

CONTACT ANGLE LOWERING OF POLYSTYRENE SURFACE BY SILVER-NEGATIVE-ION IMPLANTATION FOR IMPROVING BIOCOMPATIBILITY AND INTRODUCED ATOMIC BOND EVALUATION BY XPS

Abstract Negative-ion implantation technique is expected as an effective surface modification method for insulators of polymer, since in negative-ion implantation into insulators the charge-up potential of the surface is in several volts. Polystyrene dishes were implanted with Ag − ions in an ion energy range under 30 keV in order to bring hydrophilic property to their surface for improving surface biocompatibility of cell adhesion property, and contact angles to water were measured. Contact angle was found to be lowered to 73° by the Ag-ion implantation from an original value of 86°, and it decreased with increase in both ion dose and ion energy below 20 keV. Atomic bonds of C–O, CO, and OC–O were introduced by ion implantation, these were increased in number with increase in dose and energy of implantation. These atomic bonds were considered to bring the hydrophilic property to the polystyrene surface. Human umbilical vascular endothelial cell (HUVEC) was cultured on each sample with a 199 medium. The cell growth and attachment were observed only for Ag-implanted surfaces.

Endocyclic cleavage in glycosides with 2,3-trans cyclic protecting groups.

An endocyclic pathway is proposed as a reaction mechanism for the anomerization from the β (1,2-trans) to the α (1,2-cis) configuration observed in glycosides carrying 2,3-trans cyclic protecting groups. This reaction occurs in the presence of a weak Lewis or Brønsted acid, while endocyclic cleavage (endocleavage) in typical glycosides was observed only when mediated by protic media or strong Lewis acids. To rationalize the behavior of this class of compounds, the reaction mechanism and the promoting factors of the endocleavage are investigated using quantum-mechanical (QM) calculations and experimental studies. We examine anomerization reactions of thioglycosides carrying 2,3-trans cyclic protecting groups, employing boron trifluoride etherate (BF(3)·OEt(2)) as a Lewis acid. The estimated theoretical reactivity, based on a simple model to predict transition state (TS) energies from the strain caused by the fused rings, is very close to the TS energies calculated by the TS search along the C1-C2 bond rotation after the endo C-O bond breaking. Excellent agreement is found between the predicted TS energies and the experimental reactivity ranking. The series of calculations and experiments strongly supports the predominance of the endocyclic rather than the exocyclic mechanism. Furthermore, these investigations suggest that the inner strain is the primary factor enhancing the endocleavage reaction. The effect of the cyclic protecting group in restricting the pyranoside ring to a (4)C(1) conformation, extensively discussed in conjunction with the stereoelectronic effect theory, is shown to be a secondary factor.

Classification of Organic Reactions: Similarity of Reactions Based on Changes in the Electronic Features of Oxygen Atoms at the Reaction Sites1

Organic reactions occur as a result of complicated interactions among many factors:  structural and electronic features of reactants, reagents, catalysts, temperature, etc. In this study, organic reactions were automatically classified based on these factors. A dataset of 131 reactions was investigated focusing on the changes of electronic features on the oxygen atoms at the reaction sites by principal component analysis and self-organizing neural networks analyses. Good correlations were found between the similarities in the changes of the electronic features of oxygen atoms of the reaction sites and the similarities in the substructural transformations at the reaction sites as well as with the known reaction types. These results demonstrate that a classification based on changes of electronic features is closely related to the classifications which chemists have been establishing from various points of view. Furthermore, this indicates the possibility for the automatic and systematic classification of a...

Further Development of a Reaction Generator in the SOPHIA System for Organic Reaction Prediction. Knowledge-Guided Addition of Suitable Atoms and/or Atomic Groups to Product Skeleton

A reaction generator in SOPHIA ( for reaction by ) generates all possible product structures by reconnections of free bonds obtained by cutting all bonds of a reaction site which is automatically perceived in the input reactantt structure and additions of atoms and/or atomic groups (AAG) to the free bonds. The reaction generator has been extended to automatically recognize and add suitable AAG for suitable free bonds by utilizing knowledge base derived from a reaction database. Contents of the knowledge base are structural information of AAG and structural characteristics of sites and their environments to which the AAG are added during reactions in a reaction database. The reaction generator considers reaction conditions to recognize suitable AAG for suitable free bonds by utilizing reaction condition groups obtained by classification based on word combinations of reaction condition descriptions in a reaction database. SOPHIA also has been extended to employ the reaction condition groups for interpretati...

Novel canonical coding method for representation of three-dimensional structures

A new canonical coding method for representation of three-dimensional structures, CAST (CAnonical representation of STereochemistry), is described. CAST canonically codes stereochemistry around an atom in a molecule. The same CAST notations are given for atoms of molecules in the same conformation. The CAST code is based on the dihedral angles of four atoms that are uniquely defined by a molecular tree structure. CAST has successfully represented similarities and differences between several conformers.

Negative-ion beam surface modification of tissue-culture polystyrene dishes for changing hydrophilic and cell-attachment properties

Abstract Negative-silver-ion implantation into tissue-culture polystyrene (TCPS) dishes was investigated and it was found to modify hydrophilic and cell attachment properties of the dishes. Negative-ion implantation has an advantage of being almost free of surface charging, and is a suitable method for implantation into insulators such as polymers. Negative silver ions are used due to the antibacterial property of silver. Ag-implanted TCPS dishes had a contact angle larger than the normal value of 66° of unimplanted dishes. The contact angle of water had a strong dependence on the ion energy rather than the dose. As a cell-culture experiment, human umbilical vascular endothelial cell (HUVEC) was used in unimplanted and Ag-implanted TCPS dishes, the implantation removed the cell-attachment property of the surface. In implantation with a mask with a striped pattern, most attached cells of HUVEC were in the unimplanted region aligned along a stripe direction.

Chemical Structure Elucidation from 13C NMR Chemical Shifts: Efficient Data Processing Using Bipartite Matching and Maximal Clique Algorithms

Computer-assisted chemical structure elucidation has been intensively studied since the first use of computers in chemistry in the 1960s. Most of the existing elucidators use a structure-spectrum database to obtain clues about the correct structure. Such a structure-spectrum database is expected to grow on a daily basis. Hence, the necessity to develop an efficient structure elucidation system that can adapt to the growth of a database has been also growing. Therefore, we have developed a new elucidator using practically efficient graph algorithms, including the convex bipartite matching, weighted bipartite matching, and Bron-Kerbosch maximal clique algorithms. The utilization of the two matching algorithms especially is a novel point of our elucidator. Because of these sophisticated algorithms, the elucidator exactly produces a correct structure if all of the fragments are included in the database. Even if not all of the fragments are in the database, the elucidator proposes relevant substructures that can help chemists to identify the actual chemical structures. The elucidator, called the CAST/CNMR Structure Elucidator, plays a complementary role to the CAST/CNMR Chemical Shift Predictor, and together these two functions can be used to analyze the structures of organic compounds.

A Novel Method for Characterization of Three-Dimensional Reaction Fields Based on Electrostatic and Steric Interactions toward the Goal of Quantitative Analysis and Understanding of Organic Reactions

A novel characterization method named FRAU (Field-characterization for reaction analysis and understanding), which numerically characterizes field around molecules based on electrostatic and steric interactions with pseudoreactant, has been developed for giving numeric measures of factors controlling reactions. FRAU estimates three kinds of features (FRAU features), i.e., extent of reaction field, electrostatic features, and steric features. Power of the FRAU features as discriminators recognizing similarities and differences of characteristics of structures and roles of reagents in reactions have been examined by 39 reagents containing Mg or B atoms. Similarities in these features were analyzed with the help of a self-organizing map (SOM). Good correspondences were found between the features, structures, and the role of the reagents in reaction. The results show abilities of FRAU to give useful numeric characterization of reagents.