Sugar mimics

Intramolecular cycloaddition between an azide and an unsaturated ester (see 300) was the key step in the synthesis of triazole carboxylic acids 302 a, b, prospective anionic sugar mimics (Eq. 33) [79]. 

Other class of polyhydroxylated derivatives acting as sugar mimics consists of carbasugars i.e. sugars in which the ring-oxygen atom is replaced by the carbon atom. Their synthesis can be initiated either from achiral (or racemic) derivatives (this approach will not be dealt with) or more conveniently from simple sugars (chirons). Syntheses of these important compounds were comprehensively reviewed recently.4... 

Yasuda K, Kizu H, Yamashita T, Kameda Y, Kato A, Nash R-J, Fleet G-WJ, Molyneuk R-J, Asano N. (2002) New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii. J Nat Prod 65 198-202. 

Asano, N., Nash, R. J., Molyneux, R. J., Fleet, G. W. J. (2000). Sugar-mimic glycosidase inhibitors natural occurrence, biological activity and prospects for therapeutic application. Tetrahedron-Asymmetry, 11, 1645-1680. 

Naturally occurring cyclopentylamines are found in aUosamidin, mannostatin and trehazolin, aU of which can be regarded as sugar mimics, exhibiting inhibitory activities toward glycosidases [333]. 

Two modifications which constrain the carbohydrate into a particular conformation have been reported in which the altered sugars mimic the conformation of deoxyribose in either DNA-DNA... 

Research progress on sugar-mimic polyhydroxy alkaloids derived from plants 07CJO1337. 

Considering polyhydroxylated pyrrolidines as iminosugars and then sugar mimics, it is logical that most of the reported synthetic approaches are based on the utilization, as ring A precursors, of sugars with resident stereochemistry at C-1, C-2, and C-3 positions. 

More recent examples of cyclooctene formation have been reported where cyclization was achieved without the need for annulation. For example, Percy has reported the syntheses of difluorinated cyclooctenones en route to conformationaUy locked sugar mimics (Scheme 2.46). " These cy-clizations were aided by a judicious choice of protecting group (vide supra) RCM of benzyl-protected 47 proceeded at 2.2 mmol L in 46% yield, while the benzoyl-protected substrate 45 underwent RCM at 10 mmol in 75% yield. Collectively, these results illustrate that synthesis of cyclooctenes can be challenging, and that the outcome of such reactions can acutely depend on substrate structure. 

Scheme 2.46 Synthesis of cyclooctenone compounds en route to conformationaUy locked sugar mimics. ...

Dendrimers up to a G3 generation (octavalent) were synthesized based on the 3,5-di-(2-aminoethoxy)-benzoic acid branching unit and tested in an SPR competition assay with immobilized asialofetuin. Strong multivalency effects were observed, up to a factor of 4t)0, which reached the Hmit of the assay [47]. Even more spectacular enhancements were obtained with a divalent ligand, prepared by tethering two units of 42 onto a functionalized caHx[4]arene. A 3800-fold (1900-fold per sugar mimic) affinity eiihancement was measured by fluorescence spectroscopy, thus reaching the same potency of GMl-os [59]. 

Syntheses of various hydantocidin analogues are covered in Section 1.3 of this Chapter and in Chapter 19, and cyclic guanadinium ion sugar mimics are covered in Chapter 9. 

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