Carbohydrates, conformational analysis

Tel. 212-280-2577, fax 212-678-9039, e-mail sl model%cuchem.bitnet A user-friendly molecular modeling package for molecular mechanics and conformational searching of organic molecules, proteins, nucleic acids, and carbohydrates. Conformational analysis. AMBER-, MM2-, and MM3-like and OPLS force fields implicit solvation model. Reads Cambridge and Brookhaven PDB files. VAX, Convex, Alliant, Cray, and workstations. 

The Homans parameters have been used for both solvated and in vacuo 3 >i3 simulations. In a recent study of a tetrasaccharide model for the blood group determinant Lewis-X (P-D-Gal(l-4)[a-L-Fuc(l-3)]p-D-GlcNAc(l-3)p-D-Gal) (7), Homans and Forster proposed a protocol for carbohydrate conformational analysis. o Their protocol was composed of the six components summarized in Table 1. 

Several problems associated with the interpretation of NOE data in carbohydrate conformational analysis have been elegantly illustrated by Widmalm et al., who were able to reproduce only two of three NOE buildup curves for the disaccharide a-L-Rha(l-2)a-L-Rha... 

The computational method selected for use in carbohydrate conformational analysis depends on the data amount available and accuracy and on the project goal to find a single conformation that satisfies the experimental data or to generate a statistically accurate ensemble of conformations. Advances in... 

Key words Carbohydrate - Conformational analysis -Stereoelectronic effects - Hyperconjugation... 

Keywords Amino acids Building blocks Carbohydrates Conformational analysis Laser ablation Microwave spectroscopy Nitrogen bases... 

Carbocation Force Fields Carbocation Stabilities Comparison of Theory and Experiment Carbohydrate Force Fields Carbohydrates Conformational Analysis 1 Conformational Analysis 2 Conformational Analysis 3 Force Fields A Brief Introduction Force Fields A General Discussion Infrared Spectra Interpretation by the Characteristic Frequency Approach Natural Bond Orbital Methods Solvation Carbohydrates Transition States in Organic Chemistry Ab Initio. 

Application of NMR spectroscopy to heterocyclic chemistry has developed very rapidly during the past 15 years, and the technique is now used almost as routinely as H NMR spectroscopy. There are four main areas of application of interest to the heterocyclic chemist (i) elucidation of structure, where the method can be particularly valuable for complex natural products such as alkaloids and carbohydrate antibiotics (ii) stereochemical studies, especially conformational analysis of saturated heterocyclic systems (iii) the correlation of various theoretical aspects of structure and electronic distribution with chemical shifts, coupling constants and other NMR derived parameters and (iv) the unravelling of biosynthetic pathways to natural products, where, in contrast to related studies with " C-labelled precursors, stepwise degradation of the secondary metabolite is usually unnecessary. 

J. M. CODDINCTON and M. J. Taylor, J. Coord. Chem. 20, 27-38 (1989), and references cited therein, including those which describe its application to conformational analysis of carbohydrates and its use in separation and chromatographic techniques. 

The proton spin-lattice relaxation-rate (R,) is a well established, nuclear magnetic resonance (n.m.r.) parameter for structural, configurational, and conformational analysis of organic molecules in solution. " As yet, however, its utility has received little attention in the field of carbohydrate chemistry,... 

A. Dondoni, M. Kleban, X. Hu, A. Marra, and H. D. Banks, Glycoside-clustering round calixarenes toward the development of multivalent carbohydrate ligands. Synthesis and conformational analysis of calix[4]arene O- and C-glycoconjugates, J. Org. Chem., 67 (2002) 4722 -733. 

Several reviews have already been published on the subject, for example, the acetala-tion of alditols [4], of aldoses and aldosides [5,6], and of ketoses [7]. Some aspects of the stereochemistry of cyclic acetals have been discussed in a review dealing with cyclic derivatives of carbohydrates [8], also in a general article [9] and, more recently, in a chapter of a monograph devoted to the stereochemistry and the conformational analysis of sugars [10], Aspects on predicting reactions patterns of alditol-aldehyde reactions are reviewed within a general series of books on carbohydrates [11]. The formation and migration of cyclic acetals of carbohydrates have also been reviewed [12,13],... 

I. Braccini, C. Derouet, J. Esnault, C. Hervd du Penhoat, J.-M. Mallet, V. Michon, and P. Sinay, Conformational analysis of nitrilium intermediates in glycosylation reactions, Carbohydr. Res. 246 23 (1993), and references therein. 

This chapter is divided into two parts. The first, and major, portion is devoted to carbohydrate structure. You will see how the principles of stereochemistry and conformational analysis combine to aid our understanding of this complex subject. The remainder of the chapter describes chemical reactions of carbohydrates. Most of these reactions are simply extensions of what you have already learned concerning alcohols, aldehydes, ketones, and acetals. 

Application of mass spectrometry to stereochemical analysis in the monosaccharide series is limited by the lack of experimental studies, by the absence of a generalizing, theoretical concept based upon modem conformational analysis, and by lack of precise knowledge of the mechanism and stereochemistry of the reactions taking place in the mass spectrometer. The only investigation in which a thorough study has been made of the effect of the stereochemical features of carbohydrates upon their mass spectra is that of Heyns and Scharmann, who measured the mass spectra of a number of permcthylated methyl pentopyranosides, namely, methyl tri-0-methyl-j8-D-ribo-(13), -arabino-(14), -xylo-(lS), and -lyxo-pyrano-sides (16), and of methyl tri-Omethyl-a-D-lyxopyranoside (17). 

There are several reasons for reservations about applying the computer extrapolation of crystal structure data for carbohydrates. One is that much of the crystal structure data refer to unsubstituted sugars which are only soluble in hydroxylic or polar solvents where the conformational analysis may be complicated by hydrolysis, isomerism (muta-rotation) (12), or stereospecific solvent interactions which require a more sophisticated model. However, assuming that such chemical changes do not occur or can be suppressed, there still remain questions to be answered before the conformation observed in the crystal can be accepted as a close enough approximation to that of one or more of the rotomers which may predominate in the solution state. (a-L-Sorbose gives an example of the coexistence of two primary alcohol rotameric... 

Hphe molecular mechanism of acid hydrolysis of glycosides is rather well understood today, much confusion being resolved now by the achievements of conformational analysis of carbohydrates (1,2). With regard to the three consecutive steps of reaction (cf. Figure 1)—Le., the formation of a conjugate acid by protonation of either one of the acetalic... 

G. M. Lipkind, V. E. Verovskii, and N. K. Kochetkov, Conformational analysis of the carbohydrate chains of blood-group substances, Bioorg. Khim., 8 (1982) 963-970. 

R. U. Lemieux Newer developments in the conformational analysis of carbohydrates... 

Applications of Empirical Rules for Optical Rotation to Problems of Conformational Analysis, R. U. Lemieux and J. C. Martin, Carbohydr. Res., 13 (1970) 139-161. 

---