Heparin hexasaccharide

One key NMR-based study has focused on the evaluation of the dynamic properties of heparin-like hexasaccharides.20 The analysis of Tj, T2 and NOE 13C-NMR data of biologically active synthetic compounds has shown that the sulphation pattern strongly influences the internal dynamics, and supports the importance of the GAGs flexibility on the selectivity of the interaction with fibroblast growth factors. 

These conformer populations were confirmed by a number of n.O.e. measurements (the H2—H5 distance can act as a marker in identifying the ring form). The case of a hexasaccharide (compound 23 in Ref. 9) where the three IdoA residues yield different n.O.e. enhancements, is striking. Moreover, models computed with molecular mechanics have been put forward for the peculiar pentasaccharide of heparin. The models are in acceptable agreement with the observed vicinal coupling constants and n.O.e. values (10) (a full paper by Ragazzi, M. et al. Carbohvdr. Res.. is in press). 

SCHEME 10.12 Preparation of hexasaccharides based on heparin and HS via preactivation. TTBP, 2,4,6-tri-tert-butylpyrimidinc. 

Complex oligosaccharides as complex carbohydrates are classified into specific classes based on the presence and sequence of various multiple sugar moieties linked via functional groups at totally different positions. One of the specific functionalities of tetra-, penta-, and hexasaccha-rides is their water solubility, highly dependant on the presence of a number of 0-glycosylated and W-acetamido moieties of individual fragments. One well-known example of this classical functionality is heparin pentasaccharide. The physical properties of the most important selected complex oligosaccharides, such as tetra-, penta-, and hexasaccharides, are listed in O Table 8. 

J. Choay, J.C. Lormeau, M. Petitou, P. Sinay and J. Fareed,"Structural Studies on a Biologically Active Hexasaccharide Obtained from Heparin", Ann. N.Y. 

The synthesis of a series of amine-funetionalized heparin tetra-saccharide (117) and hexasaccharides (118, 119) was performed (Fig. 5) using a n -h 2 modular approach. The conditions of the glycosylation reactions were carefully optimized to produce efficiently the desired synthetic intermediates with an N-ben lorgrearbonyl-protected ami-noethyl spacer at the reducing end. The use of microwave heating greatly facilitates O- and N-sulphation steps. ... 

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