The glycosylation of 1,2‐trans‐diequatorial diols derived from tetrabenzoylated and tetrabenzylated D‐ and L‐chiro‐inositol with several glycosyl donors has been investigated. An unprecedented dependence of the regioselectivity on the absolute configuration of the acceptor has been found. However this trend is also modulated by the nature of the protecting groups on both the donor and acceptor, with benzoylated acceptors affording higher levels of regioselectivity. Most of the results have been rationalized by DFT calculations which indicate that stereoelectronic factors and hydrogen bonding between the donor and acceptor govern their relative orientation and determine the regiochemical outcome of the process. These studies also highlight the role of the acyl group adjacent to the OH to be glycosylated in facilitating the glycosylation reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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New and highly effective procedures for the preparation of d-chiro-inositol derivatives, essentially based on selective protection of the vicinal diequatorial diol systems present in this molecule, are reported. This selective protection affords C 2 -symmetric diaxial diols such as 4 and 5, glycosylation of

We have developed an efficient synthetic strategy to HexNH2‐α(1⇄3)‐L‐chiro‐inositol (XII−XIII) and HexNH2‐α(1⇄2)‐D‐chiro‐inositol (XIV−XV) based on the regio and stereoselective glycosylation of tetrabenzoyl‐L‐chiro‐inositol 2 and tetrabenzyl‐D‐chiro‐inositol 14. Compounds XII−XV may constitute the central structural motifs of inositolphosphoglycans, which have been proposed as putative insulin mediators, and their syntheses have been designed on the basis of biosynthetic considerations. The syntheses of XII−XIII and XIV−XV involve the selective monoglycosylation of an L‐chiro inositol diequatorial diol system (2) and a D‐chiro inositol axial/equatorial diol system (14), respectively. To establish the experimental conditions to achieve the best reactivity−selectivity balance, the glycosylation reactions were studied using D‐gluco‐ and D‐galacto‐configured 2‐azido‐2‐deoxytrichloacetimidate glycosyl donors with different reactivities. The results obtained provide a practical synthetic route and new reactivity−selectivity data. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

The stereochemical outcome of glycosylations with 2-azido-2-deoxy-D-gluco- and D-galactopyranosyl trichloroacetimidates as glycosyl donors has been investigated by using a series of chiro-inositol derivatives as glycosyl acceptors. The influence of the absolute configuration, the conformation and the conformational flexibility of the glycosyl acceptor has been studied by using different glycosyl donors under similar pre-established experimental conditions. Although the structure of the acceptor may play a role in governing the stereochemistry of these glycosylations, the results show that, in general terms, the relative influence of these factors is difficult to evaluate. For a given set of experimental conditions, the stereochemical course of these glycosylations depends on structural features of both glycosyl donor and glycosyl acceptor. It is a balance of these factors, where the structure of the glycosyl donor always plays a major role, which determines the stereochemistry of the coupling reaction. Therefore, the examples reported in the literature in which the structure of the glycosyl acceptor appears to be crucial in determining the stereochemistry of the reaction constitute particularly favorable cases which do not presently allow any further generalization.

Synthesis of New Hexosaminyl D-and L-chiro-Inositols Related to Putative Insulin Mediators. -The title compounds [cf. (IV) and (V)] are prepared via regio-and stereoselective glycosylation. -(CID, M. B.; BONILLA, J. B.; ALFONSO, F.; MARTIN-LOMAS*, M.; Eur.

The influence of protecting groups on the reactivity of glycosyl acceptors has been investigated through a series of competitive glycosylation experiments using differently substituted C2 symmetric D-chiro-inositol derivatives. It has been shown that, for a given glycosyl donor, the protective group pattern effectively modulates the reactivity of these derivatives in the glycosylation reaction.Oligosaccharides play an important role in many biological processes. 2 In spite of recent progress in glycosylation methods and strategies, oligosaccharide synthesis still requires considerable effort. The preparation and the coupling of building blocks for oligosaccharide synthesis often involve extensive protecting group manipulation. The past two decades have witnessed an increasing understanding of protecting group effects on the anomeric reactivity of glycosyl donors. 3 As a consequence of the armed-disarmed concept, the possibility of tuning the reactivity of glycosyl donors through protecting group manipulation has culminated with the 'iterative one-pot synthesis of oligosaccharides' 4,5 which has greatly simplified the preparation of complex oligosaccharides. 6 Nevertheless, much less attention has been paid to the reactivity of glycosyl acceptors. The nature of the protecting groups of glycosyl acceptors have been often proposed as a cause of glycosylation failure. 3a,7 However, the influence of protecting groups on acceptor reactivity has not been systematically evaluated. It is generally agreed 3 that the electron-donating or the electron-withdrawing effect of protecting groups may, respectively, activate or deactivate glycosyl acceptors. This effect has been long ago described 8 and more recently used to develop a chemoselective glycosylation strategy. 9 In spite of this, no attempt has been made to asses the effect of protecting groups on the relative reactivity of glycosyl acceptors through competitive experiments with the only exception of a recent study on the acceptor reactivity of the 4-hydroxy group of N-acetyl-, N-phthalimido-, and 2-azido-2-deoxy-D-glucosamine derivatives. 10In the frame of an ongoing program on the synthesis of inositolphosphoglycans as putative mediators in the insulin signalling process, we have prepared a variety of inositol containing oligosaccharides. 11-14 This work has involved extensive studies on the glycosylation of myo 11 and chiro 12-14 inositol derivatives with 2-azido-2-deoxy-D-gluco and D-galactopyranosyl trichloroacetimidates. This has offered a good opportunity to gain insight into the influence of the nature of glycosyl acceptors on the glycosylation reaction. We recently reported on the influence of steric and conformational features of the acceptor on the stereoselectivity of glycosylations. 14 We now present some observations on the influence of the protecting group pattern on the reactivity of glycosyl acceptors in the coupling reaction.In the course of our studies on putative insulin mediators, the synthesis of molecules containing the structural motif 2-amino-2...

The assistance of neighboring protecting groups with different orientations in 1,2-diol acceptors and the reactivity of both reaction partners, the donor and the acceptor, have been evaluated as factors that determine the regioselectivity of glycosylation reactions. It has been established, by experimental and theoretical studies, that the regioselectivity for the glycosylation of a given OH group can be considerably increased by the presence of groups able to form a hydrogen bond with that OH group. Moreover higher regioselectivities are observed when armed donor/activated acceptor combinations are avoided.