Acetals of sucrose

Trityl ethers and acetals of sucrose have generally been used as precursors for the synthesis of partially acylated derivatives of sucrose. Deacetalation of 3,4,3, 4 -tetra-0-acetyl-2,l 6,6 -di-0-(diphenylsilyl)sucrose (33) and 3,3, 4, 6 -tetra-0-acetyl-2,l 4,6-di-0-isopropylidenesucrose (35) with aqueous acetic acid for 25 min at 50° gave 3,4,3, 4 -tetra-0-acetylsucrose27 (34) and 3,3, 4, 6 -tetra-0-ace-tylsucrose32 (36), respectively. Synthesis of 2,3,4,3, 4 -penta-0-acetyl-... 

E. Fanton, C. Fayet, J. Gelas, D. Jhurry, A. Deffieux, and M. Fontanille, Ethylenic acetals of sucrose and their copolymerization with vinyl monomers, Carbohydr. Res. 226 337 (1992). 

Some work has also been done on the separation of acetyl derivatives of disaccharides. Thus van den Heuvel and Homing (154) first showed that octa-acetates of sucrose and a-cellobiose were amenable to GLC and Jones and Perry (178) separated a number of other disaccharides. The reducing disaccharides, however, gave broad peaks which could be improved by prior reduction. 

Trityl Ethers. Treatment of sucrose with four molar equivalents of chlorotriphenylmethyl chloride (trityl chloride) in pyridine gives, after acetylation and chromatography, 6,1, 6 -tri-O-tritylsucrose [35674-14-7] and 6,6 -di-O-tritylsucrose [35674-15-8] in 50 and 30% yield, respectively (16). Conventional acetylation of 6,1, 6 -tri-O-tritylsucrose, followed by detritylation and concomitant C-4 to C-6 acetyl migration using aqueous acetic acid, yields a pentaacetate, which on chlorination using thionyl chloride in pyridine and deacetylation produces 4,l, 6 -trichloro-4,l, 6 -trideoxygalactosucrose [56038-13-2] (sucralose), alow calorie sweetener (17). 

Cyclic Acetals. One of the most significant developments in the chemistry of sucrose was the synthesis of cycHc acetals which, despite many attempts, were not synthesized until 1974. The first synthesis of 4,6-0-benzyhdenesucrose was achieved from the reaction of sucrose with a, a-dibromotoluene in pyridine (29). Since then, many new acetalating reagents have been used to give a variety of sucrose acetals, generally by transacetalation reactions. 

Acetates. Because of the significant interest in selective acetylation reactions of sucrose, the need for a convenient and unambiguous method of identification has been recognized (34,35). The position of an acetyl group in a partially acetylated sucrose derivative can be ascertained by comparison of its H-nmr acetyl methyl proton resonances after per-deuterioacetylation with those of the assigned octaacetate spectmm. The synthesis of partially acetylated sucroses has generally been achieved either by way of selectively protected derivatives such as trityl ethers and cychc acetals or by direct selective acetylation and deacetylation reactions. 

Acetylsucrose [63648-81-7] has been prepared in 40% yield by direct acetylation of sucrose using acetic anhydride in pyridine at 40° C (36). The 6-ester has subsequently been obtained in greater than 90% yield, by way of 4,6-cycHc orthoacetate. Other selective methods for the 6-acylated derivatives include the use of alkyl tin reagents such as dibutyl tin oxide (37) and of dibutyl stannolane derivatives (38). Selective acetylation of sucrose by an enzymic process has also been described. Treatment of sucrose with isopropenyl acetate in pyridine in the presence of Lipase P Amano gave, after chromatography, 6-0-acetylsucrose (33%) and 4/6-di-O-acetylsucrose (8%). The latter compound has been obtained in 47% yield by the prolonged treatment (39). 

Orthoesters. The value of cycHc orthoesters as intermediates for selective acylation of carbohydrates has been demonstrated (73). Treatment of sucrose with trimethylorthoacetate and DMF in the presence of toluene-/)-sulfonic acid followed by acid hydrolysis gave the 6-0-acetylsucrose as the major and the 4-0-acetylsucrose [63648-80-6] as the minor component. The latter compound underwent acetyl migration from C-4 to C-6 when treated with an organic base, such as / fZ-butylamine, in DMF to give sucrose 6-acetate in >90% yield (74). When the kinetic reagent 2,2-dimethoxyethene was used,... 

An economic synthesis of (3) has been patented (74,91). The process iavolves (/) synthesis of sucrose 6-acetate by way of sucrose 4,6-cychc orthoacetate (2), and (2) selective chlorination usiag thionyl chloride—pyridine—1,1,2-trichloroethane, followed by removal of the acetate group. 

The reactive intermediate, (C2H3)2NCH2CH2C1 HCl, which is used to produce cationic starch, is made by the reaction of (C2H3)2NCH2CH20H with thionyl chloride. A synthetic sweetener (qv), sucralose [56038-13-2] is made by the reaction of sucrose or an acetate thereof with thionyl chloride to replace three hydroxy groups by chlorines (187,188). 

A crystalline 5,5 -diene, or bis (vinyl ether), derivative of sucrose has been prepared from 6,6 -dideoxy- 6,6 -diiodo-sucrose hexa-acetate, derived from the 6,6 -ditosylate, by treatment with silver fluoride in pyridine (26). 

Similar anomalous distributions are observed in other thermal product mixtures. A commercial soft caramel made by heating sucrose and 0.1% acetic acid to 160°C contained 18% of a mixture of di-D-fructose dianhydrides.94 fi-D-Fru/-1,2 2,1 - 3-D-Fru/(now assigned as a-D-Fru/-l,2 2,l -a-D-Fru/83), ot-D-Fru/-1,2 2,1 -p-D-Fru/(5), ot-D-Frup-1,2 2,l -0-D-Fnjp (4), ot-D-Fru/-l,2 2,1 - 3-D-Frup (1), and p-D-Fru/-l,2 2,3 - 3-D-Fru/ (2) were found in the ratio 4 12 1 6 2. The first three of these, constituting 68% of the mixture, are considered to be kinetic products. The authors commented on this, but did not offer any explanation. Notice, however, that the preparation of such commercial caramels commences with heating of an acidic aqueous solution of sucrose, which almost certainly results in hydrolysis. Hence, the final dianhydrides are probably derived from the reaction of fructose, rather than sucrose. 

Cf Conversion fector of sucrose to acetate (g-acetate/g-sucrose) 1.05... 

Fig. 1. Time courses of the concentration profiles of sucrose and acetate in bulk liquid phase (solid line simulation 1, short-dotted line simulation 2, long-dotted line simulation 3).

The metabolic and pharmacokinetic profile of sucralose (this is a novel intense sweetener with a potency about 600 times that of sucrose) in human volunteers was studied by Roberts and coworkers [82]. Part of this study was realized using PLC in the following chromatographic system in which the stationary phase was silica gel and the mobile phase was ethyl acetate-methanol-water-concentrated ammonia (60 20 10 2, v/v). Separated substances were scraped off separately, suspended in methanol, and analyzed by filtration, scintillation counting, or enzymatic assay. It was shown that the characteristics of sucralose include poor absorption, rapid elimination, limited conjugative metabolism of the fraction absorbed, and lack of bio-accumulative potential. 

The reaction of sucrose with a combination of 2,2-dimethoxy-propane-N,N-dimethylformamide-p-toluenesulfonic acid has been exploited to give various, interesting, cyclic acetal derivatives.32,83-85 This combination of reagents for acetonation is known to give strained, and otherwise inaccessible, acetals of monosaccharides.86-89 Treatment of sucrose with 2,2-dimethoxypropane in N,N-dimethyl-formamide in the presence of a catalytic proportion of p-toluenesul-fonic acid for 80 min at room temperature afforded a mixture containing 4,6-O-isopropylidenesucrose, 2,1 4,6-di-O-isopropyli-... 

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