Carbohydrate scaffold

The introduction of electronic asymmetry into this class of bis(diaryl)phosphinites has been used to design catalysts that can afford both enantiomers of naproxen nitrile. If the carbohydrate scaffold is based on methyl o-D-fructol uranosidc (29), (i )-naproxen nitrile is produced. In a similar manner to the results above, electron-donating aryl substituents on phosphorus afford... 

Fig. 15. Various mannosylated glycoclusters built around carbohydrate scaffolds.160-162...

F. -Y. Dupradeau, and J. Kovensky, Multi-mannosides based on a carbohydrate scaffold Synthesis, force field development, molecular dynamics studies, and binding affinities for lectin Con A, J. Org. Chem., 72 (2007) 9032-9045. 

A series of potent, linear C2-symmetric HIV-1 protease inhibitors with K, values in the nanomolar range was prepared from a diaryl bromide precursor emanating from a carbohydrate scaffold, by application of Heck, Suzuki, Stille, and cyanation reactions. Included in this series was the first reported microwave-promoted Suzuki coupling with an alkyl borane [41]. A very high-yielding Suzuki coupling is presented... 

Thionocarbamates on carbohydrate scaffolds—from synthesis to bioactivity... 

Thioxotetrahydro-l,3-0,iV-lieterocycles are commonly named cyclic thiocarbamates or thionocarbamates. The structural association of five- and six-membered thionocarbamates with diverse carbohydrate scaffolds has shown a promising potential in modern organic synthesis and in the preparation of biomolecules mimics. The principal pathways for their synthesis, the recent and most important developments of their chemical transformations as well as some examples of their biological activities will be considered in the following discussion. 

Introduction—interest of thionocarbamates connected on carbohydrate scaffolds... 

This review summarizes the most relevant methods for the preparation of thionocarbamates on carbohydrate scaffolds, the recent and most important developments of their chemical transformations and some examples concerning their biological activities. 

Thionocarbamates and carbohydrate scaffolds may be connected to give either fused, anchored or spiro compounds (Fig. 1). 

The second- and oldest-method for the preparation of thionocarbamates on carbohydrate scaffolds consists of the condensation of thiocyanic acid, generated in situ from potassium thiocyanate and a protic acid, with an anomeric-free sugar to form the thermodynamically more stable five-membered ring OZT as the major compound (Scheme 2).27,28... 

Some examples of thionocarbamates syntheses on carbohydrate scaffolds from their isothiocyanate precursors were reviewed by Ortiz-Mellet27,28 and more recently by Fernandez-Bolanos.29 The present review will consider the... 

Fig. 1 Different possibilities of thionocarbamate connection on carbohydrate scaffolds.

Saccharidic templates bearing an amino group in C-2, C-6, C-3, C-5. Generally, an amine located on non-anomeric position reacts similarly through the condensation reaction with carbon disulfide or thiophosgene, the preliminary formed isothiocyanate leads to spontaneous or base-induced cyclization into 1,3-oxazolidine- or l,3-oxazine-2-thiones, as previously mentioned. Several extensive studies are reported about the selective introduction of thionocarbamate moieties on carbohydrate scaffolds.3 22 23 320 34 38... 

One last approach to thionocarbamates on carbohydrate scaffolds was developed in D-Fru series the intermediate imino sugar (2R,3R,4R,5R)-2,5-bis(hydroxymethyl)-3,4-dihydroxypyrrolidine (DMDP) obtained in... 

The condensation of DMDP with carbon disulfide/dicyclohexylcarbodiimide (DCC) afforded the indolizine derivative—potentially biological active thionocarbamate on carbohydrate scaffold, fused from the nitrogen side. 

Methods for the A-acylation of similar heterocycles, such as simple thiazolidinethiones, have been reported since 1977, namely acyl chlorides in miscellaneous conditions,586 or carboxylic acids under DCC-activation.60,61 However the easiest and most effective method involves acyl chlorides or carboxylic anhydrides in the presence of an amine.47 Applying that procedure on carbohydrate scaffolds Rollin and co-workers62 reported the synthesis of diverse /V-acylated OZTs. The reactions were performed with good yields and the /V-selective acylation was ascertained by NMR— namely the thiocarbonyl 13C chemical shift (Scheme 41). Thanks to the dual nature of the carbanion drifting in the reaction,596 60 no competitive formation of the thioester, as mentioned by Plusquellec el al. in the case of benzothiazole, was observed. 

We report here some literature examples 13, 55 of A-vinylsulfonylation and reduction to A-vinyl derivatives. Reactions were applied to different types-fused, anchored, spiro-OZTs on carbohydrate scaffolds and the examples shown indicate that the location of the OZT moiety with respect to the anomeric carbon can sometimes influence the results obtained. 

With respect to OZTs anchored on carbohydrate scaffolds, the direct replacement of the sulfur by oxygen showed to be tricky (Scheme 51). 

In general OZT moieties in carbohydrates scaffolds are very important structures due to the wide range of biological and pharmaceutical applications. But many further applications still remain to be developed. 

In summary, it was shown that a thionocarbamate function can be connected on carbohydrate scaffolds according to three different possibilities fused, anchored and spiro. Each linkage can be selectively obtained depending on the synthetic pathway and/or the carbohydrate backbone. 

Other carbohydrate scaffolds with synthetic interest have also been investigated by NMR. For instance, the factors driving the conformational preferences of methyl azido-trideoxy-hex-5-enopyranosides have been discussed based on the analysis of the 1H-1H coupling constants which afford conformational information.61... 

Scheme 2.2.5.10 RhuA stereoselectivity screening using structurally defined aldehydes based on carbohydrate scaffolds.

Structural relationships suggest that the extended carbohydrate scaffolds obtainable by such tandem aldolizations may be regarded as metabolically stable mimetics of oligosaccharides, in particular of C-glycosides that are hydrolytically stable. The latter class of compounds shares an interest for potential therapeutic applications with the class of so-called aza sugars that have commanded attention in recent years as potent glycoprocessing inhibitors for the treatment of diabetes and other metabolic disorders, as well as for the blocking of viral or microbial infection and metastasis. 

Sugar amino acids (Saa) 1 are carbohydrate scaffolds that carry an amino and a carboxy function.12 Due to their structural and functional diversity, no detailed nomenclature for this class of amino acids has yet been established. Saa are found in nature as subunits of oligosaccharides (neuraminic acid 1) in cell walls of bacteria (muraminic acid 2) and in some antibiotics 3-6 (Scheme l). 2-8 ... 

The C2-symmetric diphosphinite and CVsymmetric phosphinite-phosphate ligands, based on a carbohydrate scaffold, and iridium complexes give catalyst precursors that are active in the hydrogenation of imines. Cationic iridium complexes gave rise to catalytic systems that were more active than the neutral iridium complexes. Enantioselectivities up to 76% were obtained.347... 

Additionally, the environmental issue of utilizing waste cellulosic material and waste biomass products should be considered as an alternative green chemistry application to the production of many value added products. The combinatorial utilization of carbohydrate scaffolds based on chiral building block functionalization will also constitute attractive and relatively cheap starting materials. This rich selection of potential approaches, combined with further developments of new procedures and modem reagents, creates an enormous opportunity for the field to be at the frontier for many years to come. 

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