Carbohydrate synthesis solid-phase linkers

Photolabile linkers play an important role in solid-phase organic synthesis (SPOS) due to their stability under both acidic and basic conditions. The ONb photolabile linker was modified to improve cleavage rates and yields Fmoc-Tos-OFI was released in 87% yield after 23 h (Scheme 4) [24]. Specifically, the primary alcohol was changed to a secondary benzylic alcohol and the attachment to the resin was through an alkyl chain as opposed to an amide function. Linker 20 was used for the production of carboxylic acids or carbohydrates. A second example... 

The fhioethyl group present in the anchor group of (40) was activated by treatment with N-iodosuccinimide (NIS) followed by displacement with a variety of alcohols (44-46). To prove the possible application of this linker in solid phase carbohydrate synthesis, protected glycosides (47) and (48) were coupled to linker (40) and released enzymatically. Flitsch et al. also described the immobilization and enzymatic cleavage on a variety of amines [41]. Nevertheless, the application of this enzyme-labile hnker group in multi-step syntheses on the solid phase and subsequent enzyme-initiated release from the polymeric support has not been described yet. 

A survey of the literature reports regarding the synthesis of (3-lactam using carbohydrate precursors has recently been published by Furman et al. [215]. They have shown that the carbohydrates were used either as chiral tools or chiral auxiliaries. A few solid phase approaches have been outlined in the survey using the vinyl ether bound to the polymeric support through a sulfonyl linker. Two alternative modes of attachment of the vinyl ethers to the resin have been reported. 

An automated solid-phase method necessitates a polymer support and a linker that are compatible with the reagents used in carbohydrate synthesis. Several strategies have been developed that address functional group compatibility and swelling of the polymer support. Of these strategies, a family of olefinic linkers has proven to be readily cleaved under neutral... 

D. Weigelt, G. Magnusson. A linker for solid phase carbohydrate synthesis, permitting the introduction of variable anomeric functionality in the release step. Tetrahedron Lett. 1998,39,2839-2842. 

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