Esters anhydro derivatives

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. 

Imidazole-l-sulfonyl esters of a-D-galactopyranoside derivatives are easily transformed to their corresponding 3,6-anhydro derivatives [78] at room temperature in dry DMF, by intramolecular participation of 3-O-methyl substituent (Scheme 16). Formation of... 

Anguibactin (470) is a unique siderophore (microbial iron-transport compound) isolated from iron-deficient cultures of a fish pathogenic bacterium, Vibrio anguillarum (378). The structure of 470 was determined by X-ray diffraction studies of its anhydro derivative. Another related compound copurified with 470 was identified as 2-(2, 3 -dihydroxyphenyl)-thiazoline-4-carboxyiic acid methyl ester (471) (379). 

In erythromycin-11,12-carbonate (11), the cyclic ester locks the structure of the ring predominantly into the 6,9-hemiketal, with only a minor amount of the 9-keto form present [36, 77-79]. As a consequence, the facile dehydration of the 6,9-hemiketal to the 8,9-anhydro derivative (8) is inhibited. The increased stability results in better potency, pharmacokinetics, and tissue penetration than erythromycin [80, 81]. However, concerns about potential hepatotoxicity have prevented its wider usage [71, 82, 83]. 

Replacement of the C-8 proton of erythromycin with a less labile substituent prevents dehydration of erythromycin-6,9-hemiketal (18, X=H) to the 8,9-anhydro derivative (8). Flurithromycin (19) was obtained via mutational biosynthesis by feeding 8(5 -fluoroerythronolide A to a biosyntheti-cally-blocked mutant strain of S. erythraea [117]. The starting material for bioconversion was prepared by treating 8,9-anhydroerythronolide-6,9-hemiketal with trifluoromethyl hypofluorite [118]. The 2 -ethylsuccinate ester of flurithromycin is now in clinical trial [119]. 

Some of the ester derivatives of polysaccharides, such as cellulose acetates or nitrates, are of considerable industrial importance (Chapter XII). Those of the sugars have not been commercialized to any great extent, with the possible exception of sucrose octaacetate. An important series of surface-active materials are provided by alditols and their anhydro derivatives partially esterified with long-chain fatty acids (Chapter VII). For the latter derivatives, increased solubility in water is provided by reaction with ethylene oxide. 

Alditols, particularly glycerol (I), ethylene glycol, sorbitol, and D-manni-tol, have widespread commercial applications, frequently as a result of their hygroscopic properties. The organic monoesters, particularly of long-chain fatty acids, may have surface-active properties which make them of interest as emulsifiers, but the usual conditions of commercial esterification produce anhydro derivatives simultaneously (Chapter VII). Nitrate esters are important as explosives and as pharmaceuticals. The acetal derivatives (Chapter IV) have been extensively prepared and studied, but as yet have found no practical application. 

The use of 2-substituted amino-3-aminopyridines (or corresponding 3-substituted amino-2-amino, 3-substituted amino-4-amino and 4-substituted amino-3-amino derivatives) gives the corresponding TV-substituted pyridopyrazinones with esters or alloxan, or with diketones gives quaternary salts such as (403) or their anhydro bases (404) e.g. 56CB2684, 78HCA2452). 

Deoxyhalogeno sugars are susceptible to nucleophilic attack, leading either to displacement, elimination, or anhydro-ring formation. The ease of displacement decreases in the order I > Br> Cl > F the iodo and bromo derivatives have, therefore, been especially utilized in such reactions, although several reactions with chlorodeoxy sugars have now been reported as a result of the increased availability of these compounds. The approach delineated in Section 11,1 (see p. 227) for predicting the reactivity of sulfonic esters can be expected also to be applicable, in an approximate and qualitative way,... 

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