Carbohydrate Epimerization

II. Stereospecific Ester Activation in Nitrite-Mediated Carbohydrate Epimerization... 

Based on the efficient multiple carbohydrate esterifications and Lattrell-Dax carbohydrate epimerization, novel and convenient double parallel- and double serial inversion methods have been developed, by which methyl p-D-mannosides and methyl P-D-talosides have been efficiently synthesized in very high yields at very mild conditions in few steps. The results also indicate that an ester group can, either in parallel or serially, induce its two neighboring groups in the epimerization reacriom... 

Dong, H. Pei, Z. C. Ramstrom, O., Stereospecrfic ester activation in nitrite-mediated carbohydrate epimerization. J. Org. Chem. 2006,71, 3306-3309. 

Commercial A -acetylneuraminic acid aldolase from Clostridium perfringens (NeuAcA EC 4.1.3.3) catalyzes the addition of pyruvate to A-acetyl-D-mannosamine. A number of sialic acid related carbohydrates are obtained with the natural substrate22"24 or via replacement by aldose derivatives containing modifications at positions C-2, -4, or -6 (Table 4)22,23,25 26. Generally, a high level of asymmetric induction is retained, with the exception of D-arabinose (epimeric at C-3) where stereorandom product formation occurs 25 2t The unfavorable equilibrium constant requires that the reaction must be driven forward by using an excess of one of the components in order to achieve satisfactory conversion (preferably 7-10 equivalents of pyruvate, for economic reasons). 

Uzan et al. have reported an alternative route to 1,2-fused thionocarbamates from 1,2-carbohydrate sulfites.49 The reaction proceeded via formation of a -configured thiocyanate, which further epimerizes to the ot-anomer, ready to undergo cyclisation into the fused OZT (Scheme 36). 

Keywords Carbohydrate Chemistry, Carbohydrate Protection, Epimerization, Inversion, Dynamic, Regioselective Control, Neighboring Group Participation... 

Epimerization of carbohydrate stractures to the corresponding epi-hydroxy stereoisomers is an efficient means to generate compounds with inverse coirfiguration that may otherwise be cumbersome to prepare. Several different synthetic methods have been developed, including protocols based on the Mitsunobu reaction,sequential oxidation/reduction... 

During this epimerization process, it was found that the reactivity in the 4-position was however much higher than in the 2-position. At room temperature, the epimerizatiou reaction in the 4-position occurred instantaneously, completed withiu teu to tweuty minutes, whereas in the 2-position the epimerization reaction proceeded very slowly under these conditions. This result incited us to make use of the reactivity difference between the different positions to develop a new method, stepwise inversion of the hydroxyl groups amounting to a double serial inversion protocol, by which carbohydrate structures where one position is a hydroxyl group and the other positions were protected with ester groups could be obtained. 

Carbohydrate ketones.J This reagent is recommended for oxidation of carbohydrate alcohols to ketones without epimerization of axial a-substituents to the more stable cpimcrs. Ru04 has been used successfully, but is expensive when used in stoichiometric amounts as required for consistent results. 

L-lduronic acid synthesis Synthesis of L-iduronic acid residues occurs after D-glucuronic acid has been incorporated into the carbohydrate chain. Uronosyl 5-epimerase causes epimerization of the D- to the L-sugar. 

Although molecular rearrangements of carbohydrate inflates are rare, they are not unknown [2,21,31]. Many of these rearrangements are ring-contraction reactions associated with treatment of Inflates with lithium triethylborohydride [see Eq. (10) 20,21]. Reported rearrangement reactions occurring when halide or azide ions are the nucleophiles are quite rare and are restricted to epimerization at centers next to a carbonyl group. Such reactions have been reported only for the more basic fluoride [32] and azide ions (Scheme 5) [33],... 

The method employing triphenyl phosphite methiodide, as adapted to carbohydrates,130 has been used for the synthesis of protected 4-deoxy sugars. From methyl 2,3-di-0-methyl-6-0-p-tolylsulfonyl-a-D-glucoside and the corresponding D-galactoside, epimeric 4-iodo derivatives were obtained these were both reduced to methyl 4-deoxy-2,3-di-0-methyl-b-0-p-tolyl-sulfonyl-a-D-zj/Zo-hexoside. 

An intramolecular radical cyclization on carbohydrate derivatives was the method developed by Lundt and Homeman in a highly stereocontrolled synthesis of functionalized cyclopentanes [9]. Due to the neutral conditions required for the cyclization step, which prevented competing side reactions such as P-elimination and base-promoted epimerization, the potential of the employed radical intramolecular reaction versus the classical carbanionic carbon-carbon bond forming reactions was demonstrated. 

Predict which carbohydrates mutarotate, which reduce Tollens reagent, and which undergo epimerization and isomerization under basic conditions. (Those with free hemiacetals will, but glycosides with full acetals will not.) Problems 23-58, 62, 63, and 66... 

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