Effect of the Aglycon

Rate Constants and Kinetic Parameters for the Hydrolysis of -D-Glucopyrano8ide8  

Ivanov and coworkers,in an investigation of the effect of keto groups in the aglycon, foimd that the ease of hydrolysis of the 8-D-glucopyrano-sides studied is in the order 3-acetoxypropanonyI (38)iS 2,3-dihydroxy-propyl (39) methyl (1). 

TimeU also examined the influence, on the rate of hydrolysis, of the size of the aglycon (see Table IX). He concluded that steric hindrance is of no importance, not even in the case of neopentyl /3-n-glucopyranoside. However, in this series of jS-n-glucopyranosides, in which the aglycon is equatorially attached in the stable Cl (n) conformation, there is a slight 

The increased rate of hydrolysis of a 2-propyl glycoside over a 1-propyl glycoside has also been observed by Konkin and coworkers (see Table XXI). This result is in agreement with the theory that the secondary alcohols are better leaving-groups because of their greater stability. 

The rate constant for the hydrolysis of tert-butyl /S-D-glucopyranoside is about 1000 times as great as that for methyl -D-glucopyranoside in 1 M perchloric acid at 25°. TimelF found the factor to be about 500 in 

---

It is of interest now to note the somewhat unpredictable effects of the aglycon portion, the substituents at C-2, C-3, and C-6, and the nature of the nucleophile in related displacement reactions. Owen and... 

In the case of the methyl D-fructofuranosides, there is a relationship to the D-arabinofuranosides, with a different type of C-l, C-2 interaction. Here, the hydrogen atom on C-l has been replaced by a hydroxymethyl group, and the difference in the C-2 interactions with the C-3 hydroxyl group should be small for the anomers the effect of the aglycon group (OMe) and the hydroxymethyl group will probably be similar. 

The term exoanomeric effect was introduced to describe an orientational effect of the aglycon part.31 In this case, the electron density of the lone pair of the exocyclic oxygen atom is transferred to the antibonding orbital of the endocyclic C—O bond (Figure 1.12). Essentially, this effect... 

While the steric and electronic effects of the aglycone Z-R in Fig. 1) showed a modest, yet discernible, improvement on the selectivity of the reaction,substit-uents on the ligating phosphorus had the most pronounced effect [6,7]. Hydro-... 

The conformational effect of the aglycon in alkyl glycopyranosides has been examined with the methyl, ethyl, isopropyl, and tert-butyl tri-0-acetyl-/3-D-ribopyranosides, and the corresponding benzoates. In each series, there was a negligible change in conformational population as between the methyl, ethyl, and isopropyl derivatives, but the terf-butyl derivatives contained somewhat less of that con-former [IC(d)] having the aglycon axially attached, presumably because there is loss of some rotational freedom about the C-1-0-1 bond in the tert-butyl derivatives as a result of steric hindrance. 

After the discovery by Malaprade 92) that polyhydroxy compounds were oxidized by periodate ion, Fleury and co-wOrkers 93) pointed out that the reaction is selective for hydroxyl groups on adjacent carbon atoms and results in chain scission. Hudson and co-workers 9Jf) developed periodate oxidation into an extremely convenient method for structural studies in carbohydrates 95). Because of the masking effect of the aglycon on the reducing carbon, the methyl glycosides are particularly suitable materials for this type of analysis. The method involves the determination of the molar ratios of oxidant consumed and of formic acid and formaldehyde produced. D-Mannitol, for example, consumes five moles of oxidant and produces four moles of formic acid and two moles of formaldehyde. 

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

Koch and coworkers49 found that the C-l shifts of isopropyl and tert-butyl a-D-glucopyranoside respectively lie 4 and 7.7 p.p.m. to higher field than that of the methyl glycoside this was assumed to be wholly due to the y-effect between methyl groups of the aglycons and the an-omeric centers. Isopropyl a-D-glucopyranoside can exist as three retainers 3, 4, and 5, and it may be seen that the last two contribute to... 

The turning of the key once the complex has formed is a separate issue. In this regard, Lemieux (47) has pointed out that rotation about the glycosidic bond must weaken the exo-anomeric effect and thereby importantly activate the anomeric carbon to nucleophilic attack. Therefore, it seems likely that the role of the key hydroxyl group of the aglycon is to accommodate the rotation prior to the attack by water to form / -D-glucopyranose, which is the first product of the reaction. 

The application of standardized UV (or UV-Vis) spectroscopy has for years been used in analyses of flavonoids. These polyphenolic compounds reveal two characteristic UV absorption bands with maxima in the 240 to 285 and 300 to 550 nm range. The various flavonoid classes can be recognized by their UV spectra, and UV-spectral characteristics of individual flavonoids including the effects of the number of aglycone hydroxyl groups, glycosidic substitution pattern, and nature of aromatic acyl groups have been reviewed in several excellent books. ... 

In Table I, the more stable anomer is listed first. In each of the four cases, this anomer is the Irans-C 1 -C2-aldofuranoside, having a Irons relationship of the aglycon group to the hydroxyl group at C-2. Thus, the 0-d anomers of methyl D-ribofuranoside and methyl D-xylofuranoside are listed first, even though the interactions for the latter are equal. Later in this Chapter, the effect of this conformational stability will be discussed in relation to formation of products At present, it suffices to mention that there are two factors to be considered, the C-l and C-2 interactions, and the overall interactions (C-l and C-2, C-2 and C-3, C-3 and C-4). The... 

Saponins are widely distributed in plants and are a particular form of glycosides. They are so-called because of their soaplike effect, which is due to their surfactant properties. They also have hemolytic properties and, when injected into the bloodstream, are highly toxic. When taken by mouth, saponins are comparatively harmless. According to the structure of the aglycone or sapo-genin two kinds of saponin are recognized, the steroidal and triterpenoid type. 

In Ref. 1 (pp. 1114-1115) the effect of the axial or equatorial orientation of the aglycon in the rate of oxidation of a number of /f-D-glycopyranosides is described. When the aglycon adopts an equatorial orientation [a / anomer in the 4Ci(d) conformation] the oxidation takes place at a higher rate (two to ten times) than for the a anomer. In the case of methyl L-arabinopyranosides, the a-L anomer, which, in the (l) conformation has an equatorially attached group at C-l, is oxidized more rapidly. 

---