Intramolecular Transfer Processes 1,8 in Complex Carbohydrate Systems

Intramolecular hydrogen transfer (IHT) radical reactions involving six- and seven-member transition states are very common, while those via seven-member transition states are scarce. Recently, our group has pioneered an unusual 1,8-TIH process in (1→4)-O-disaccharides systems promoted by the 6-O-yl radical that occurs via a nine-member transition state between the two disaccharide units.

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The regioselectivity of this process is very dependent on the stereochemistry of the four chiral centres involved (C5, C4, C1' and C5'). Thus it has been established that when the trioxocane ring can be formed in a stable chair-boat conformation, abstraction takes place preferably on carbon 5' (1,8-TIH), as in b-maltose. In addition, when the generation of this 6-O-yl radical takes place under reductive conditions, one of the monosaccharides of the D to L series can be selectively transformed from the system to D-Glcp-(1→4)-D-Glcp to bL-Idop-(1→4)-D-Glcp, an interesting fragment similar to the one present in heparin and heparan sulphate, glycosylaminoglycans related to numerous metabolic functions.

Currently, our objective in this line of research is to design new structures of cyclodextrins (CDs), natural cyclic oligosaccharides composed of glycopyranosyl units in 4C1 conformations united in a very similar way to b-maltose (a-1,4-glicosidic bonds) and that present a high potential due to their capacity of inclusion with a great variety of molecules.

Access to these new CD structures is via the radical protocols established in our 1,8-TIH group that allow remote functionalization from one unit to another, transformations difficult to obtain by conventional methods. The three most common CDs are used as precursor substrates and the conditions developed in our laboratory are applied: an oxidative one to generate trioxocane rings from the primary hydroxyl groups and another reductive one that modifies the D-glucose unit to L-idose and therefore originates an investment in chair conformation.

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In both cases, CD structures are expected with noticeable deformations in the cavity and consequently, selectivity differences when encapsulating molecules.