Carbasugar

In the last twenty years, nitro sugars became powerful chemical tools on account of their usefulness for the construction of carbon-carbon bonds prior to the transformation of the nitro group into a variety of other chemical functionalities. As a result, a diverse range of funcionalized carbohydrates and other derivatives as carbasugars, cyclitols and heterocycles have been prepared. 

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... 

Besides these general methods a number of others such as 1,3-dipolar cycloaddition, aldol condensation etc. are applied to prepare carbasugars. 

Monocyclic carbasugars. The 1,3-dipolar cycloaddition was used in the synthesis of polyhydroxylated compound with the seven-membered ring (Fig. 16).29... 

Fig. 16 Application of cycloaddition for the synthesis of 7-membered ring carbasugar derivatives.

A general method for the preparation of carbasugars with various ring size consists of the metathesis of properly prepared sugar diolefins. 

An interesting 6-cxn-dig radical cyclization leading to carbasugars was reported by Lopez (Fig. 28).42... 

Fig. 26 Carbasugar derivative obtained by intramolecular aldol condensation.

Fig. 28 Application of radical reaction in the synthesis of carbasugar derivatives.

Bicyclic derivatives. Polyhydroxylated carbo-bicyclic derivatives may be regarded as carbasugars with the rigid structure resulting from the presence of the additional carbocyclic ring. The most convenient way for construction of the bicyclic skeleton consists of the Diels-Alder reaction of properly functionalized trienes (intramolecular version) or dienes and olefins (intermolecular). 

Application of simple sugars as starting materials for the preparation of optically pure complex products represents nowadays the classic methodology of organic synthesis it is covered by many comprehensive reviews, cited here only in references.88 These references provide the precise state-of-art in the synthesis of aza sugars, carbasugars and other derivatives. 

Gabosines which have been isolated from Streptomyces strains constitute a family of keto carbasugars, most of them possessing a trihydroxylated cyclohexenone structure. Because of their interesting bioactivities, a large number of synthetic approaches to these compounds have been proposed (for example [115, 116]). The shortest route (four to five steps) to gabosines I and G was accomplished starting... 

Lundt I (2003) Iminosugars, isoiminosugars, and carbasugars from activated carbohydrate lactones efficient synthesis of biologically important compounds. In Witzak ZJ, Tatsuta K (eds) Carbohydrate synthons in natural products chemistry synthesis, functionalization and applications. ACS Symposium Series, vol 841. American Chemical Society, Washington, DC,pp 117-140... 

The 2-oxygenated lactone 67 was reduced by means of sodium borohydride to give the protected carbasugar 72, which by hydrolysis yielded carba- -D-manno-furanose (73). Similarly, the 2-amino substituted lactone 70b was reduced to carba-5-amino-5-deoxy-a-L-glucofuranose (74) [98a] (Scheme 15). 

In our early work, we attempted the alkylation of the amine 81 with various carbohydrate triflates, namely 82-84 [57]. Somewhat disappointingly, the main products isolated were the alkenes, e.g. 85 and 86. Only a small amount of the desired N-linked carbasugar, e. g. 87 was ever obtained. At one stage we attempted an alkylation of the amine 81 with the triflate 82 and with the triflate 84 in the presence of potassium carbonate to our surprise, carbamates were formed, 88 and 89 These two carbamates have subsequently been deprotected to give the methyl -o-glucoside 90 and the free sugar 91, interesting candidates for enzyme inhibition studies [57]. 

The intramolecular nitrone cycloaddition (INC) has been used particularly for the synthesis of amino carbasugars [60, 61]. The following scheme illustrates this strategy (Scheme 16) [60], The cycloaddition of nitrone derived from lactol 49 and an excess of N-methylhydroxylamine occurs from the least hindered face affording the isoxazolidine 51 (85% yield). The amino carbasugar 52 was obtained after the cleavage of the N-0 bond. 

Iminosugars, Isoiminosugars, and Carbasugars from Activated Carbohydrate Lactones Efficient Synthesis of Biologically Important Compounds... 

Highly Functionalised Cyclopentanes and Cyclohexanes Synthesis of Carbasugars... 

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