Hydrolysis anhydro compounds

SE-52 at 160°. Similarly, l,6-anhydro-/ -D-glucofuranose corresponds to /J-D-xylopyranose. These anhydro compounds must be formed in the acid-hydrolysis stage, and they give incorrect values for D-xylose unless their presence is detected 78 this may be done by operating the column at 135°. 

In the first case, typical reactions are the formation of the methyl fi-D-glucoside from a-D-glucopyranosyl fluoride and of its 2-amino-2-deoxy derivative from 2-amino-2-deoxy-a-D-glucopyranosyl fluoride, on treatment with sodium methoxide in methanol. The products from the reaction of aqueous bases with the glycosyl fluorides depend on the concentration of alkali. At low concentrations, the normal hydrolysis products are formed. At higher concentrations of base, if the proper (trans) steric relation exists between C-6 and the fluorine atom at C-1, anhydro compounds are formed, as in (21) from (20). 

The racemization apparently takes place before hydrolysis. Similar results have been obtained with D-xylitol 5-phosphate and n-mannitol 6-phosphate. 1,4-Anhydro-ribitol is also formed from the treatment of ribitol with dilute mineral acid. However, since the anhydro compounds are produced more readily from the phosphates than from the unsubstituted alditols, it has been suggested that the latter compounds are not formed as intermediate products. The mechanism of this reaction has been explained by assuming protonation of the ester oxygen atom, with subsequent intra-... 

The stability of these 2,5 -anhydro nucleoside derivatives (38-41) which displayed antiviral activity, as well as compound 42, were determined at pH 7.5 and 2.0 (Table 4).l This was performed to determine if the biological activity of this class of compounds was due to the anhydro compound itself, or whether hydrolysis of the 2,5 -anhydro linkage occurred in solution to yield the parent compound which, as previously shown, had antiviral activity. All of the compounds tested are stable at neutral pH, with half-life values ranging from 60.5 h for 2,5 -anhydro-3 -azido-5-bromo-2, 3 -dideoxyuridine (40) to >168 h for 3 -azido-2, 3 -dideoxy-5-methylisocytidine (42). At low pH, however, the compounds displayed shorter and more variable half-lives, ranging from 11.3 min for 2,5 -anhydro-3 -azido-2, 3 -dideoxyuridine (38) to 140 min for 3 -azido-2, 3 -dideoxy-5-methylisocytidine (42). Pyrimidine base formation was not detected from any of these compounds. Moreover, the compounds decomposed to yield 7.5% or less of the parent compound after one half-life at either neutral or acidic pH, except for 18% of 2,5 -anhydro-3 -azido-2, 3 -dideoxyuridine (38), which was recovered as AZDU (1). 

Conversion of the C-2 amide to a biologically inactive nitrile, which can be further taken via a Ritter reaction (29) to the corresponding alkylated amide, has been accomphshed. When the 6-hydroxyl derivatives are used, dehydration occurs at this step to give the anhydro amide. Substituting an A/-hydroxymethylimide for isobutylene in the Ritter reaction yields the acylaminomethyl derivative (30). Hydrolysis affords an aminomethyl compound. Numerous examples (31—35) have been reported of the conversion of a C-2 amide to active Mannich adducts which are extremely labile and easily undergo hydrolysis to the parent tetracycline. This reverse reaction probably accounts for the antibacterial activity of these tetracyclines. 

Deoxy-D-jcylo hexose 6-(dihydrogen phosphate) (21) has also been synthesized (2) the reaction sequence makes use of 3-deoxy l 2,5 6-di-O-isopropylidene D-galactofuranose (16), a compound that can be easily prepared from D-glucose (2, 60). The mono-isopropylidene derivative (17) formed by partial hydrolysis of the di-ketal is converted into the 6-tosylate (18) by reaction with one molar equivalent of p-toluenesulfonyl chloride. From this the epoxide (19) is formed by reaction with sodium methoxide. Treatment of the anhydro sugar with an aqueous solution of disodium hydrogen phosphate (26) leads to the 6-phosphate (20)... 

The identification of L-iduronic acid as the major glycuronic acid constituent of heparin proved to be a much slower process than the identification of the amino sugar residue. Although this compound was detected in acid hydrolyzates of heparin116117 and heparin oligosaccharides,118 its yield was usually poor, because of the drastic conditions used for the acid hydrolysis (which are known to lead to extensive destruction of uronic acid).119120 Also, L-iduronic acid escaped detection as L-idose in the hydrolyzates of carboxyl-reduced heparin, probably because L-idose is readily converted into 1,6-anhydro-L-idose under the usual hydrolytic conditions. 

A branched-chain iodo sugar derivative, l,5-anhydro-4,6-0-benzyl-idene-2,3-dideoxy-3-C-(iodomethyl)-D-rifoo-hex-l-enitol [4,6-O-ben-zylidene-3-deoxy-3-C-(iodomethyl)-D-allal] (200), is one of the products formed on treatment of methyl 4,6-0-benzylidene-2,3-dideoxy-a-D-en/thro-hex-2-enopyranoside (77) with the Simmons-Smith reagent (diiodomethane and zinc-copper couple).123,212 Compound 200 displays high solvolytic reactivity, an observation that has been rationalized by supposing the formation of the highly stabilized carbonium ion213 (201). Thus, under conditions wherein methyl 2,3,4-tri-0-acetyl-6-deoxy-6-iodo-a-D-glucopyranoside required more than 24 hours to react appreciably with an excess of silver nitrate in 50% aqueous p-dioxane buffered with silver carbonate, the iodide 200 was hydrolyzed completely in less than 1 minute the product of hydrolysis of 200 is the cyclopropyl aldehyde 202. Methanolysis of... 

In the 3,4-anhydro-arabinose series, only the hydrolysis of the anomers of methyl 2-0-acetyl-3,4-anhydro-D-arabinopyranoside with aqueous acetic acid appears to have been studied 68 both compounds undergo substitution at C-3, with participation of the acetoxyl group, leading to the corresponding D-lyxose derivatives. 

Both of these classes of compounds differ only in the location of the oxygen atoms and display similar properties. They are stable in alkaline solutions, but are hydrolyzed in acids at approximately the same rate. Nevertheless, this hydrolysis is slower than with ordinary alkyl hexofuranosides. An equilibrium is established between free hexoses and their anhydro derivatives in aqueous acid solution, which in general contains only minor proportions (about 13%) of 1,6-anhydrofuranoses... 

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