Septanosides

An elegant route to derivatives of septanose from the open-chain hexoses has been reported (Fig. 43).59 The protected septanose 137 was converted in few standard steps into free septanosides. 

A distinction must be made between septanosides that lack (6-unsubstituted) or contain (6-substituted) an exocyclic hydroxymethyl group at C-6. In the same way that D-glucose can form a septanose ring by connecting the 6-hydroxyl group to the anomeric center as in Fig. 1, all of the common aldohexoses can adopt a septanose... 

Fig. 6. Septanosides 120-124 prepared by Jayaraman via the ring expansion/oxepine approach.

SCHEME 26. Septanoside used as a donor to prepare a diseptanoside, compound 164. 

Recently McDonald et al. reported the synthesis of (1 —> 5)-linked D-mannoseptanosyl di- and trisaccharides.80 Once again they utilized differentially protected phenyl 1-thio-a-D-mannoseptanoside as donor and methyl a-D-mannoseptanoside as acceptor to synthesize the di- and tri-a-septanosides exclusively. The strategy used for their synthesis mirrored that depicted in Scheme 26. The septanoside structures and their properties in a glycosidase assay are presented in Section IV. 

In addition to the major strategies previously outlined, other methods have also been utilized to synthesize septanosides. Among these, a bis-aldol addition of nitroalkanes onto pyranose-derived dialdehydes has been utilized to synthesize 3-nitro- and 4-nitro-septanosides.81-84 Such septanose derivatives are useful as they... 

There are several instances where reactive intermediates present during the synthesis of septanosides have reacted intramolecularly to give ring-contracted or bicyclic products.91 Similar intramolecular reactions (such as the formation of 1,6-anhydro sugars) have precedents in the pyranose literature. Such cases of intramolecular reactivity described in the literature notably involve novel ethers or thioethers as the nucleophilic species in the ring contractions. 

SCHEME 30. Septanosides reacting intramolecularly to give ring-contracted or bicyclic products. 

FIG. 11. Left Low-energy conformations of seven-membered rings. Right Different views of methyl a-D-g/ycero-D-ido-septanoside (198). Shown are wedge-and-dash, chair conformation, and two-labeled T conformers, illustrating how the T nomenclature works. 

Fig. 13. Conformational map of C-6-unsubstituted septanosides. Left A pseudorotational wheel of septanose conformations. Solid ovals mark conformations of P-septanosides, dashed ovals a-septanosides. Right Septanosides and the conformers that have been observed for them.

Fig. 15. Different perspectives of the methyl 2-deoxy-a-D-g/nco-septanoside (210) structure from X-ray data.

A parameter that has been useful for defining the anomeric stereochemistry of glycopyranosides is the chemical shift of the anomeric carbon atom, C-l. Similarly, the 13C NMR shifts of C-l in methyl septanosides also diagnostic for their anomeric configuration. In general, the Sc.i values for a-septanosides are slightly upfield (99-104 ppm in completely deprotected septanosides) relative to (S-septanosides (104-111 ppm) (Table I). This distribution of chemical shifts mirrors the trends for pyranosides namely, the C-l chemical shifts for a-pyranosides lie upfield from those of p-pyranosides. This observation suggests that the anomeric effect is operative in... 

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