Pyranosides exocyclic cleavage

The roles of nucleophilic assistance and stereoelectronic control in determining endo-versus exo-cyclic cleavage of pyranoside acetals have been investigated for a series of a- and j8-anomers.15 Exocyclic cleavage of a-anomers, via a cyclic oxocarbenium ion, is predicted by the theory of stereoelectronic control, and was found exclusively for the cases studied. The endocyclic route, with an acyclic ion, is predicted for the /1-structures, and a measurable amount was found in all cases, but its extent was dependent on temperature, solvent, and the nature of the aglycone group. 

The exocyclic cleavage pathway is taken by all common pyranosides evidence includes ... 

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). 

Liras, J. L., Lynch, V. M., and Anslyn, E. V. "The Ratio between Endocyclic and Exocyclic Cleavage of Pyranoside Acetals is Dependent upon the Anomer, the Temperature, the Agy Icon Group, and the Solvent." /. Am. 

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. 

Liras, J. L. and Anslyn, E. V. (1994) Exocyclic and Endocyclic Cleavage of Pyranosides in Both Methanol and Water Detected by a Novel Probe, J. Am. Chem. Soc. 116, 2645-2646. 

Liras JL, Anslyn EV (1994) Exocyclic and endocyclic cleavage of pyranosides in both methanol and water detected by a novel probe. J Am Chem Soc 116 2645-2646... 

Using Isotopic Scrambling to Distinguish Exocyclic vs. Endocyclic Cleavage Pathways for a Pyranoside... 

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