Mannose 2,5-anhydro

Deoxy-sugars. Part XXV. Structure and Reactivity of Anhydro-sugars. Part II. Derivatives of 3 6-Anhydro-D-mannose, 3 6-Anhydro-2-deoxy-D-galactose, and 3 6-Anhydro-2-deoxy-D-g ucose," A. B. Foster, W. G. Overend, M. Stacey, and G. Vaughan,/. Chem. Soc., (1954) 3367-3377. 

More-specific methods are available for identifying and quantitating the typical, amino sugar component of heparin (and some heparan sulfate species), namely, 2-deoxy-2-sulfoamino-D-glucose. Most of these methods are based on conversion of these residues into 2,5-anhydro-D-mannose by deamination with nitrous acid (see Section VIII,2). The 2,5-anhydro-D-mannose residues may be determined either colorimetrically,52-54 or fluorimetrically.55... 

From pig mucosa. Notations as for Scheme 1. Major products (yield 40-80% of original heparin). Major disaccharide fraction (50-80%). From heparin chains terminating with a D-glucuronic acid residue at the reducing end. Minor products (yield <3% of original heparin). From the active site for antithrombin (asterisk denotes 3-C-sulfation of the amino sugar or anhydro-D-mannose). 

A possible electron circuit in this complex reaction is shown in LXVIII and the products of the completed reaction in LXIX. The h-ans-arrangement of the hydroxyl on C4 and the aldehyde group (Cl) in LXIX makes the establishment of a furanose ring sterically unlikely and consequently 2,5-anhydro-D-mannose (chitose) probably exists as an dldehydo-mga,T. 

C-Nucleoside analogue 464 of this ring system was prepared (86SC35) from 2,5-anhydro-3,4,6-tri-0-benzoyl-L-mannose dimethyl acetal 462 and 6-(2-aminophenyl)-3-methylthiotriazin-5(2//)-one 463 in the presence of acetic and hydrochloric acids. 

In contrast to other 2,5-anhydroaldoses (which exhibit mutarota-tion, possibly due to the formation of hemiacetals28), 2,5-anhydro-D-glucose does not show any mutarotation.27 The importance of this compound as a potentially useful precursor to C-nucleosides warrants a reinvestigation of the deamination reaction, and the definitive proof of the structure of the compound. The readily accessible 2,5-anhydro-D-mannose (11) does not possess the cis-disposed side-chains at C-2 and C-5 that would be required of a synthetic precursor to the naturally occurring C-nucleosides, with the exception of a-pyrazomycin (8). The possibility of an inversion of the orientation of the aldehyde group in 11 by equilibration under basic conditions could be considered. 

To accommodate these facts, the earliest mechanisms proposed for degradation of D-fructose assumed that it was present in the furanose form, and that the ring remained intact. It was assumed that the initial reaction was the elimination of water, to form the 1,2-enolic form of 2,5-anhydro-D-mannose, and that further dehydration resulted in 2-furaldehyde. The necessity for D-glucose to isomerize to D-fructose was assumed to account for the much lower reaction-rate of D-glucose. This mechanism does not account for the observation that 2,5-anhydro-D-mannose is less reactive than D-fructose, nor is there any evidence that 2,5-anhydro-D-mannose is present in reacting D-fructose solutions. Nevertheless, similar mechanisms have since been proposed.13-16 Because of the ease of mutarotation of D-fructose... 

Lemieux and Fraser-Reid174 have reported that the reaction of methyl 3,4,6-tri-0-acetyl-2-deoxy-2-iodo-j3-D-glucopyranoside (137) with bromine and silver acetate in acetic acid containing potassium acetate gives an almost quantitative yield of 1,3,4,6-tetra-O-acetyl-2,5-anhydro-D-mannose methyl hemiacetal (139), obtained as an... 

The key sequence in the determination of the structures of 2,5-anhydro-D-mannose (2) and -D-talose (4) was their reduction to the corresponding 2,5-anhydroalditols (5 and 6) and identification of the asymmetric dialdehyde (7) resulting from oxidation of the anhydro-alditols with periodate.37,43... 

Levene15 reported that heating of 2-amino-2-deoxy-D-mannose (8) in the presence of silver oxide leads to a crystalline, nitrogen-free compound to which he attributed the structure of 2,5-anhydro-D-glucose on the basis of its elemental analysis. The possibility of interconversion between the two chair forms Cl (d) — 1C (d), which would bring the amino group at C-2 into equatorial orientation, has been postulated.22 Without excluding this possibility, it remains to be proved that the deamination by silver oxide does, indeed, proceed by... 

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