C-glycosyl compounds

C-glycosyl residue, to give either the aglycon or degradation products thereof. 

Studies of ultraviolet and infrared spectra of compounds of this class yield valuable information as to the structure of the aglycons. The use of infrared spectra in recognizing C-glycosyl compounds is complicated by the number and variety of oxygen functions, and, so far, little progress has been made. Studies on nuclear magnetic-resonance spectra have obvious promise, once suitable solvents or appropriate derivatives of the compound under examination, or both, are available. 

Barbaloin was first isolated in 1851, but an acceptable structure was not proposed until 1952, when Miihlemann showed that condensation of aloe-emodin anthrone Ql,8-dihydroxy-3-(hydroxymethyl)anthrone, 7, R = CH2OH] with tetra-O-acetyl-a-D-glucopyranosyl bromide in acetone in 

Oxidized with periodate at 0° in the dark, one mole of barbaloin rapidly consumes 2.0 moles of the oxidant, with the production of one mole of formic acid, and no further oxidation takes place during a further 24 

The biogenesis of barbaloin has not yet been studied, but its synthesis gives rise to some legitimate speculations thereon. A phenoxide ion can be alkylated on an oxygen atom or on a carbon atom, as shown in the reaction sequence below which reaction predominates depends on the phenol, the conditions employed, and the alkylating agent used. The glycosylation of the anion from aloe-emodin anthrone is an example of reaction b, whereas 

Koeppen has reported that homoorientin, orientin, and barbaloin yield glycerol on oxidation with periodate, followed by reduction with sodium borohydride and acid hydrolysis. A similar result had been reported earlier for mangiferin, which is now known to be a C-glycosyl compound (see p. 360) and it is clear that this method cannot reliably differentiate C-glycosyl compounds and glycosides. 

Comparison of the ultraviolet and infrared spectra of barbaloin with those of the cascarosides suggested that at least one of the phenolic groups in the barbaloin residue of the cascarosides is free. 

In a later paper, Fairbairn and Simic described the cascarosides as primary glycosides of barbaloin and chrysaloin (11-deoxyaloin) and mentioned that about four have been identified. 

Previous doubts as to whether mangiferin (6) is a difficultly hydrolyzed D-glucoside or a C-D-glycosyl compound have now been resolved, and 

The earlier workers had been led astray by the results obtained on periodate oxidation of vitexin itself, which yields a compound, named dehydro-secovitexin, C2iH280io, which contains the same number of carbon atoms as vitexin. This compound was formulated as the dialdehyde (10). Horowitz and Gentili confirmed that this oxidation causes no loss of carbon (contrary to the suggestions of Rao and Venkateswarlu ), and formulated the product as the bis(hemiacetal) (11) derived from the dialdehyde (12). This observation serves to emphasize the importance of carrying out periodate oxidations on materials that have a nonsugar component which is unable to influence the reaction. 

---

C-Glycosyl compounds have a carbon atom ia place of the exocycHc oxygen atom of the acetal group and, therefore, are branched cycHc ethers. An example is the naturally occurring anthroquiaone dye, carminic acid [1260-17-9] (Cl Natural Red 4). 

Fischer projection of acyclic form, 56-57 glycosides, 132-135 C-glycosyl compounds, 139-140 N-glycosyl derivatives, 137-139 glycosyl halides, 136-137 glycosyl residues, 125 isotopic substitution and isotopic labelling, 91 me so forms, 59 optical rotation, 59 parent structure choice, 53... 

The anion of nitromethane adds easily to the carbonyl functions of sugars. This is a useful strategy for extension of the carbon chain.100 2-Acetamido-2-deoxy-P-D-glucose (A-acetyl-D-glucosamine) is the carbohydrate unit of glycoproteins that occurs most often. The nitromethy-lation method provides a straightforward route to a series of C-glycosyl compounds with the acetamido functionality (Eq. 3.62).101... 

A few years later, the same group extended this strategy in order to access metabolically stable C-glycosyl clusters containing long-arm spacers via a sequence of transition metal-catalyzed transformations (Scheme 11).93 In this context, crossmetathesis reactions of various C-glycosyl compounds with alkenes having available... 

These model reactions were of great value in the extension of the C-glycosylation reaction with malonic esters to five-membered ring-systems. Treatment of 2,3 5,6-di-O-isopropylidene-a-D-manno-furanosyl bromide122,123 (150) with diethyl sodiomalonate led to an anomeric mixture of C-glycosyl compounds that could be separated by column chromatography, with the a (151) and /B (152) anomers in... 

The formation of the desired C-glycosyl compounds was found to be much more favored when nonparticipating groups were present in the starting halide. Thus, treatment of 2,3,5-tri-0-benzyl-/3-D-ribofuranosyl chloride124 (158) with diethyl sodiomalonate gave a mixture of the expected C-glycosyl compounds that were isolated as the benzoates (161 and 162) in 44 and 46% yields, respectively. The... 

Ohrui and Fox128 reported that treatment of 2,3-O-isopropylidene-5-O-trityl-jS-D-ribofuranosyl chloride (171) with diethyl sodiomalonate in 1,2-dimethoxyethane gave an anomeric mixture of C-glycosyl compounds (172) which, when allowed to equilibrate in ethanol containing sodium ethoxide, gave the )3 anomer (173) as the preponderant product. Similar observations were made with the C-... 

The scope of the acid-catalyzed formation of C-glycosyl compounds has been greatly expanded with the finding that enol ethers and ketene acetals can be used as the carbon source in electrophilic substitution reactions at the anomeric center.126 Treatment of 198 with the trimethylsilyl enol ether derived from cyclohexanone, in the presence of stannic chloride, led to 2-(2,3,5-tri-0-benzoyl-/J-D-ribofuranosyl)cyelohexanone (206), presumably by way of the inter-... 

Another approach to functionalized C-glycosyl compounds consists in the condensation, catalyzed by stannic chloride, of 1-O-acetyl-2,3,5-tri-0-benzoyl-j8-D-ribofuranose (198) with terminal al-kenes.126 153 Treatment of 198 with 1-hexene in the presence of stannic chloride gave a C-D-ribofuranosyl derivative (213) in high... 

Moffett and coworkers203 reported the synthesis of several 4-/3-D-ribofuranosylpyrazoles, such as 284(a-c), by 1,3-dipolar cycloaddition of diazoalkanes to the alkenic C-glycosyl compound 283, followed by dehydrogenation of the resulting pyrazolines. In view of the known biological activities of several nucleosides containing the... 

Kishi and co-workers have proposed that O-glycosides and C-glycosyl compounds share the same conformational characteristics in solution.34 This is the case, for instance, for the C-disaccharide 27 (Fig. 15).35 It adopts a major conformation similar to that proposed for methyl 3-<9-(a-n-galactopyranosyl)-a-D-mannopyranoside (28). 

Stereoselective methods for the preparation of 1,2-cw-O-glycosides and 1,2-cw-C-glycosyl compounds are presented. 

---