Carbohydrate isosteres

Pseudosugars are yet another class of stable carbohydrate isosteres which are resistant to both chemical and enzymatic hydrolysis at the pseudoanomeric center. Understandably, for the construction of highly functionalized carbocycle the natural choice would be to take advantage of chiral templates to install the chirality endowed on their periphery. A novel [3 + 3]-annulation reaction was planned by a Michael-Wittig reaction between a chiral enal and yUde in which the chirality of the cyclohexane could be drawn from the y-chiral hydroxy group of the enal. 

C-Furanosyl compounds embody tetrasubstituted tetrahydrofurans which are analogs of naturally occurring furanosides, in which the anomeric oxygen has been replaced by a carbon atom, providing a non-labile ether functionality in place of the biochemically crucial acetal linkage. C-Furanosyl compounds occur widely in nature, and have been used as carbohydrate isosteres. We undertook preliminary molecular modelling studies on D-jylofuranosylethyne derivatives (Fig. 3), which we... 

S. M. Andersen, M. Ebner, C. W. Ekhart, G. Gradnig, G. Legler, I. Lundt, A. E. Stiitz, S. G. Withers, and T. Wrodnigg, Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors, 1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-D-mannitol Syntheses and glycosidase inhibitory activities of l,2,5-trideoxy-2-fluoro-l,5-imino-D-glucitol and of l,2,5-trideoxy-l-fluoro-2,5-imino-D-mannitol, Carbohydr. Res., 301 (1997) 155-166. 

The carbohydrate-based 1,3,2-dioxathiolane A, -dioxide 23 (Section 6.05.3.1) has demonstrated an exceptional anticonvulsant activity in the standard maximal electroshock seizure test. Compound 23 is much more potent than structural analogs, and approximately 8 times more potent than the isosteric topiramate <1998JME1315>. 

Other carbohydrate based analogues of zanamivir which have been synthesized as potential influenza virus sialidase inhibitors include the sulfur isostere (37), which was prepared from the known [113] 6-thio-Neu5Ac derivative (38) via a sequence analogous to that shown in Scheme 1.2 for the preparation of zanamivir [114]. The sulphur isostere (37) was found to have comparable activity (IC50 = 5 x 10 9 M) to zanamivir [114]. 

For the purposes of this chapter, the term polyhydroxy phosphonic (or phosphinic) acid is used in the widest possible context, and some discussion is therefore directed towards those carbohydrate analogues, both isosteric and non-isosteric, of true natural carbohydrate molecules, and which include at least one direct phosphorus-carbon bond ... 

H.L. Arth, W.-D. Fessner, Practical synthesis of 4-hydroxy-3-oxobutylphosphonic acid and its evaluation as a bio-isosteric substrate of DHAP aldolase, Carbohydr. Res. 305 (1998) 313-321. 

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