1.7- Anhydro derivatives

The rare 4-membered (trimethylene oxide) anhydro ring is represented in 3,5-anhydro-l,2-0-isopropylidene-D-xylose 34) and l,3-anhydro-2,4-0-methylenexylitol 35). 

The 6-membered (pentamethylene oxide) anhydro ring is present in methyl 2,6-anhydro-a-D-altroside 36) and in the naturally occurring 1,5-anhydrohexitols, styracitol and polygalitol. 

Peat (anhydro sugars). Advances in Carbohydrate Chem. 2, 37 (1946). 

Methods of Preparation a. Alkaline Elimination of Halogen or Sulfonic Ester Groups 

Other sugar esters that readily undergo displacement, rather than hydrolysis, under alkaline conditions are the methanesulfonates, sulfates 39), and, to some extent, the nitrates 40). No clear-cut example of displacement under alkaline conditions of a sugar phosphate ester has been recorded 41). (See Chapter III.) 

On treatment with aqueous potassium hydroxide for 40 h on a steam bath,32 phenyl /3-maltose heptaacetate (40) was converted into the 1,6-anhydride 41, isolated in 72% yield as its acetate (42). Compound 42 

6-anhydride adopts the C4 conformation45 despite the axial glycosyl-oxy group on C-4. 

Attempts66 to prepare the 2,3-anhydride from methyl 3-0-(methyl-sulfonyl)-/3-maltoside, using M sodium methoxide, resulted in the corresponding 3,6-anhydride 43. To circumvent the formation of 43, the reaction was performed with methyl 3-0-(methylsulfonyl)-6,6 -di-0-trityl-/3-maltoside. The desired product, methyl 2,3-anhydro-4-0-(2,3,4-tri-0-acetyl-6-0-trityl-a-D-glucopyranosyl)-6-0-trityl-/3-D-allopyrano-side (44), was obtained in 72% yield. Attempted detritylation of 44 by brief treatment with hydrogen bromide in glacial acetic acid, followed by conventional acetylation, gave methyl 2,6,2, 3, 4, 6 -hexa-0-acetyl- 

3-bromo-3-deoxy-/3-maltoside (45) in 85% yield. Compound 45 must have arisen from diequatorial ring-opening, by attack at C-3 in 44 by the bromide anion. Had the reaction had Sn2 character, the epoxide would have had to react by way of the 5H0 conformation 46, so that the 2- and 3-substituents would be held antiperiplanar in the conformation 47 first formed. However, the approach of the bromide anion to 

Synthesis of methyl 3,6 3, 6 -dianhydro-/3-maltoside has been achieved by alkaline alcoholysis of the 6,6 -di-0-(methylsulfonyl) or 6,6 -di-0-p-tolylsulfonyl derivative of methyl /3-maltoside.20,23 Similar treatment of methyl 2,3,2, 3, 4 -penta-0-acetyl-6-deoxy-6 -0-p-tolyl-sulfonyl-/3-maltoside with ethanolic sodium hydroxide for 3.5 h at 60° afforded methyl 3, 6 -anhydro-6-deoxy-/3-maltoside in 90% yield.90 

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Similarly, anhydro derivatives of monosaccharides and disaccharides readily react with 359 to give the respective carba-di- and -tri-saccharide. 

Likewise, complete synthesis of acarbose was conveniently accomplished by use of the anhydro derivative 392b prepared from maltotriose. Condensation of 392b with optically active 359 afforded two products, one of which was, after deprotection, shown to be identical to an authentic sample of acarbose. 

Direct conversion of the 6-sulfonates of D-galactopyranosides into their 6-deoxy-6-fluoro derivatives is usually hindered, because of the polar field-effect exerted by the lone electron pairs of the axial 0-4 (Ref. 158). Thus, the 6-0-mesylgalactoside 294 gave ° the 3,6-anhydro derivative 297 (23%) as the only isolated product on reaction with CsF in boiling ethanediol. How-... 

The influence of other radicals in the stabilization of dihydroxytetrahy-drofuran rings should also be considered, as, for example, the p-toluene-sulfonic esters.41 When the compound LXI is hydrolyzed by acids, it gives the 2,5-anhydro derivative (LXII), whereas the compound LXIII gives D-glucitol. 

Remarkable selectivity has been observed in the oxidation of molecules containing several secondary hydroxyl groups, such as al-dopentopyranosides, 6-deoxyaldohexopyranosides, cyclitols, and various anhydro derivatives. As indicated previously, attack usually occurs at relatively hindered hydroxyl groups. When aqueous solutions of benzyl /3-D-arabinopyranoside, benzyl jS-D-ribopyranoside,... 

The Wittig reaction, or its phosphonate modification, can be a very useful reaction in the synthesis of anomerically functionalized precursors to C-nucleosides, particularly when the ring-closure reaction leads to five-membered, anhydro derivatives, and occurs with a high degree of stereocontrol. Zhdanov and coworkers,130 showed that the following five-membered, Wittig products (179-182) were formed from various free sugars and (p-methoxybenzoyl)- and (acetyl-methylene)-triphenylphosphoranes. 

Internal-displacement reactions to give sugar anhydrides are well known, and anhydro derivatives of sucrose have been prepared by treatment of the respective sulfonates or chlorides with a base. Buchanan and coworkers described the synthesis of 3, 6 -anhydrosucrose by treating 2,3,4,6,l, 3, 4 -hepta-0-acetyI-6 -0-(p-ni-trophenylsulfonyl)sucrose with sodium ethoxide in ethanol for 2 h under reflux.18 Similar treatment of 2,3,4,l, 3, 4, 6 -hepta-0-acetyl-6-chloro-6-deoxysucrose (46) with sodium methoxide in methanol, followed by acetylation, gave crystalline 2,4,l, 3, 4, 6 -hexa-0-acetyl-3,6-anhydrosucrose (47) in 83% yield.81 The H n.m.r. spectrum of 47... 

The tetracycline which may be present is then converted to an anhydro derivative by heating in acid and is measured spectrophotometrically. Feldman et al. (84) developed the alkaline degradation method to measure CTC in fermentation mash and Spock and Katz (85) used this method to determine CTC in animal feed premixes. 

Other Methods for Glycoside Synthesis Dehydro and Anhydro Derivatives... 

Anhydro-D-dulcitol (XXXV) has been prepared by a method which demonstrates its structure. Hockett and coworkers11 prepared it from methyl 3,6-anhydro-a-D-galactopyranoside but both the anhydride itself and its tetraacetate were liquid. Carr63 obtained another anhydro derivative of dulcitol by heating it with phosphoric acid. This also was a liquid but gave rise to a crystalline dibenzoate and a dicarbanilate and was a dianhydro derivative, but no constitutional studies have yet been carried out on this substance. 

The 5,6-anhydro derivatives of D-sorbitol and D-mannitol41 69 behave in like manner to the 5,6-anhydro-l,2-isopropylidene-D-glucofuranose of Freudenberg and coworkers.70 Thus, 5,6-anhydro-l,3 2,4-diethyli-dene-D-sorbitol (LXXXV) readily suffers ring scission with ammonia to give 6-amino 6-desoxy-l,3 2,4-diethylidene-D-sorbitol (LXXXVI)69 or with sodium methoxide to form 6-methyl-l,3 2,4-diethylidene-D-sorbitol.42 l,2 3,4-Diisopropylidene-5,6-anhydro-D-mannitol gives rise... 

A small number of fluorinated analogs has been prepared without prior protection of the hydroxyl groups, but, owing to the strongly basic conditions prevailing, such reactions as concurrent formation of the 3,6-anhydro derivative (7) may occur, as in the fluorination of methyl 6-O-p-tolylsulfonyl-a-D-glucopyranoside (6) with potassium fluoride in 1,2-ethanediol.77 A previous attempt to use this reaction, in... 

Anhydro derivatives of 2,4-dideoxy-2-fluoro-/3-D-xyZo-hexopy-ranose and 2,3-dideoxy-2-fluoro-/3-D-rtfco-hexopyranose, and the corresponding, reducing sugars, have been synthesized from 1,6-anhydro-... 

On studying the KDO content of LPS from Xanthomonas sinensis, Volk and coworkers64 found that only one KDO residue per LPS chain is present in this organism. Moreover, the authors observed the formation of 4,7- and 4,8-anhydro derivatives (39 and 40) of KDO (see Scheme 14) under the conditions used for mild hydrolysis of the LPS with acetic acid. Free KDO was also shown to yield the anhydro derivatives under analogous conditions. The structures of these unusual side-products were identified by mass spectrometry, as follows. Reduction of 39 and 40 with sodium borohydride gave the two epimeric mixtu.es, 41 and 42. These were subjected to periodate treatment followed by borohydride reduction, the products separated by paper electrophoresis, and their trimethylsilyl ether derivatives analyzed by... 

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