Anhydro compounds stability

The condensation of acetone with D-ribose, with sulfuric acid as the catalyst, has also been examined in detail.17 The major component is 2,3-O-isopropylidene-D-ribofuranose (59%), together with three minor components l,5-anhydro-2,3-0-isopropylidene-D-ribofuranose (9%), 1,2 3,4-di-O-isopropylidene-a-D-ribopyranose (3%), and 1,2-0-isopropylidene-a-D-ribofuranose (6%). The authors observed that the only marked difference when other catalysts (such as copper sulfate or zinc chloride) were used was the absence of the anhydro compounds. Assuming that the 1-hydroxyl group is equatorial, the preponderance of the 2,3-acetal is consistent with the thermodynamic stability of the isomer having the least number of endo substituents and with the unfavorable interactions between the acetal rings in the 1,2 3,4-diacetal, which possesses a cis-syn-cis arrangement of rings.10... 

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). 

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. 

The stability of 5-substituted anhydro-5-amino-l,2,3,4-oxatriazolium hydroxides (6) depends on the nature of the substituent and decreases from very stable to moderately stable compounds in the order RSO2 > RNHCO > RCO > R <94MI 418-0 >. 

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... 

Due to their extremely polar character, tetracyclines bind with proteins to form conjugates that are difficult to extract from biological matrices. Use of dilute mineral acids is of great help in dissociating tetracyclines from proteins, but once in aqueous solution, their exfraction into volatile organic solvents for further concentration and cleanup is hampered by the unfavorable partition coefficients. Most of these antibiotics are photosensitive compounds, whereas all of them show poor stability under strong acidic and alkaline conditions with reversible formation of the 4-epi-tetracyclines in weakly acidic conditions (pH 3), and anhydro-tetracyclines in strong acidic conditions (below pH 2). 

Compounds containing methylene groups activated by both a cationic ring and another electron-withdrawing group easily form stable anhydro-bases, e.g. (636) — (637), (638) — (639). Stabilization is also achieved by utilization of the aromatic character of the cyclopentadiene anion or the pyrrole anion compounds of type (640 Z = NR, O, S) and (643) readily lose protons to give the mesomeric anhydro-bases (as 641 <- 642) which are called pseudoazulenes. 

The ease of formation of alcoholates and adducts can be related to both the acidity and the geometry of the poly hydroxy compound. The geometry is important, in that the chelate ring must possess a minimum of strain in order to allow the complex to possess the maximum stability. Reaction of a cyclic 1,2-diol with a metal hydroxide is physically impossible if the hydroxyl groups are oriented in directions that are exactly opposite (180°) to each other. Cyclic 1,3-diols can form chelates if both of the hydroxyl groups are cis and axial. An example of this is the reaction of 1,6-anhydro-... 

Probably most significant is the observation that presence of an anhydro ring may, like presence of an acetal ring, confer stability on a primary sulfonyloxy group (c/., compounds 5 and 8 12 and 13 27 and 30, for example). 

Anhydro-5-hydroxyoxazolium hydroxides lacking substituents at C(4) dimerize spontaneously by a process in which one molecule acts as an electrophile and the other as a nucleophile (Scheme 21). This accounts for the fact that dimeric products of this type are obtained by the action of dicyclohexylcarbodiimide on acylamino acids of the general formula R1C0NR2CH2C02H. Substituents at position 4 stabilize the mesoionic system the first compounds to be prepared were the acetyl derivatives (220) (B-49MI41800) and (221) (58Cl(L)46l) and much of the more recent work has been carried out with the relatively stable methyldiphenyl compound (222). This miinchnone decomposes above 115 °C to yield the allene (225) with loss of carbon dioxide. The mechanism proposed for this remarkable reaction (Scheme 22) involves valence isomerization to the ketene (223), which undergoes a 1,3-dipolar cycloaddition with the miinchnone. The product loses carbon dioxide to form a new betaine (224), which collapses to the allene as shown. 

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