Thioethyl glycosyl donors

SOLID SUPPORT GLYCAL ASSEMBLY VIA THIOETHYL GLYCOSYL DONORS 25... 

Conversion of 26 to the protected thioethyl glycosyl donors 27 was achieved through epoxidation with dimethyldioxirane to yield the 1,2-anhydro sugar, followed... 

The concept was based upon the ability to control the reactivity of thioethyl and selenophenyl glycosyl donors by careful choice of anomeric substituent and hydroxyl protecting groups. Selenoglycosides are more reactive than their sulfur analogs and therefore four different levels of reactivity can be attained using only one promoter system (NIS/TfOH) (Fig. 4). As iodonium transfer to the sulfur or selenium atom is rapid and reversible under the conditions of the reaction, only the most reactive glycosyl donor in the mixture is activated when one equivalent of NIS is used. Sequential addition of NIS and acceptor units thus allows the rapid, controlled synthesis of complex carbohydrate structures. 

To install the appropriate functionality at C2, solution phase chemistry has relied on a trans-diaxial addition of an iodonium electrophile in the presence of an amine to form an iodosulfonamide. Displacement of iodine proceeds presumably through an aziridine intermediate and may be induced by a thiolate nucleophile to fashion thioethyl 2-amidoglycosyl donors [38]. Successful transfer of this method to the solid support allowed polymer-bound glycals to be converted into thioethyl gly-cosyl donors. These donors were in turn coupled with a variety of glycosyl acceptors, including glycals [39]. 

On the other hand, the reactivity-tuned coupling of selenophenyl donor 92 and thioethyl glycoside 93, mediated by NIS/TMSOTf, proceeded smoothly to give the disaccharide 94 as a single anomer in 77% yield. The Aloe group was selected to control the a-selectivity of the glycosylation reaction. 

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