Hydrolysis of pyranosides

The implications of the above observations may be important, especially if similar trends are observed in pyranose anomers. For example, with respect to the mechanism of acid-catalyzed hydrolysis of pyranosides, endocyclic C-0 bond cleavage (preceeded by 05 protonation) may be assisted in P-anomers in which the Cl-01 bond is equatorial, since the 04-Cl bond may already be extended in these anomers. By a similar argument, exocyclic C-0 scission (preceeded by 01 protonation) may be assisted in the hydrolysis of a-pyranosides in which the Cl-01 is axial and extended, thus resembling the transition state. Post and Karplus have recently suggested that enzyme-catalyzed glycoside hydrolysis of P-pyranosides may indeed take place by ring oxygen protonation, followed by endocyclic C-0 bond scission. 

Hydrolysis of pyranosides follows the trend observed for other compounds where the hydrolysis proceeds through an A-1 mechanism having positive AS values. Overend and coworkers calculated AS values at 60° for the hydrolysis of 24 pyranosides. All are positive, ranging from -f 4.1 to -1-23.0 cal. mole deg. all but two are greater than -f 10.0 cal. mole deg., and the mean is - - 13.7 cal. mole deg. h They compared their values with those reported for the acid-catalyzed hydrolysis at 25° of sucrose (- -7.9), ethyl orthoformate (-f5.8), and ethylal (diethoxy-methane) (-f-7.3), aU of which are known to proceed by the A-1 mechanism, and with the values calculated by Capon and Overend from the results of Heidt and Purves for the hydrolysis of methyl, benzyl, and phenyl a- and /3-n-glucopyranosides (mean, - -13.6). Many other values in the same range have been reported and are listed in Section VI (see pp. 91-100). 

Rate Constants and Kinetic Parameters for Hydrolysis of Pyranosides"... 

As described in Section 11,1, hydrolysis of pyranosides involves, as the rate-determining step, heterolysis of the conjugate acid (2) to a cyclic, carbonium-oxonium ion (3) which has the half-chair conformation (6) having C-2, C-1, 0, and C-5 in one plane. Therefore, the formation of (3) involves a net counterclockwise rotation about the C-2 to C-3 and C-4 to C-5 bonds. According to Feather and Harris, the rate of hydrolysis is controlled by the resistance to rotation counter to the net effect. They stated that it is probable that transient, structural distortions are responsible for this behavior, and that the conjugate acid might assume a... 

It seems reasonable to assume that this is the normal route for acidic hydrolysis of pyranosides. Exceptions include the hydrolyis of tert-butyl (3-D-glucopyranoside, which is cleaved at the oxygen-ferf-butyl bond.215... 

The hydrolysis of pyranosides is postulated to largely proceed via exocyclic cleavage to give a cyclic oxocarbe-nium ion (Path A). Yet, it has long been recognized that an alternative pathway is also possible—namely, endocyclic cleavage to give an acyclic oxocarbenium ion (Path B). 

With this ortho ester good selectivity for the axial alcohol is achieved in the acidic hydrolysis of a pyranoside derivative." ... 

Duroux, L. et al.. Insight into napthoquinone metabolism 3-glucosidase-catalysed hydrolysis of hydrojuglone 3-pyranoside, Biochem. J., 333, 275, 1998. 

In their study of Bronsted acid induced cleveage of a [with axial C(l)-OMe] and (3 [with equatorial C(l)-OMe] glycopyranosides, Fraser-Reid et al.46 demonstrated that the (3/a rate ratios for hydrolysis of methyl pyranosides (Table 5) can be explained by the different intermediates and transition-state structures through which proceed the heterolysis of a and [3 isomers (Fig. 18). 

Table 5 p/a rate ratios for hydrolysis of methyl pyranosides... 

Fig. 1. —Reaction Mechanism for the Acid Hydrolysis of(a) 2-Aminoethy] /3-d-G1uco-pyranoside and (b) Methyl 2-Amino-2-deoxy-/3-D-glucopyranoside.

An entropy value for the acidic hydrolysis of ethyl 0-D-galactofuranoside was reported by Overend and coworkers.136 The negative value (—7.1 e.u.) was interpreted as being diagnostic of an A-2 mechanism, in contrast to the positive values (+13.7 e.u., mean value) and A-l mechanism found for a large number of pyranosides. The proposed intermediate is shown in formula (34). It was considered that the planar, furanoid ring is capable of... 

The two hexosans D-glucosan < l,4>/9< 1,6> and D-galactosan-<1,4>o<1,6> are 1,6-anhydrides of the furanose forms of the sugars and may be looked upon as internal hexofuranosides. In view of the generally more rapid acid hydrolysis of furanosides, such as methyl D-glucofuranoside or sucrose, as compared with normal pyranosides, the behavior of these hexosans toward acid hydrolysis is noteworthy. 

When methyl a-L-sorboside was methylated and the resulting penta-methyl derivative was hydrolyzed, a tetramethyl-L-sorbose was obtained. Oxidation of the latter with nitric acid gave dextrorotatory dimethoxy-succinic acid126 (LVII), from which fact it became evident that a normal pyranoside structure is present in the methyl a-L-sorboside, since this dimethoxysuccinic acid could only have arisen if carbons 4 and 5 were methylated. From a comparison of the rate of hydrolysis of ethyl a-L-sorboside126 with the methyl a-derivative the authors assumed that it... 

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