THE RATIO BETWEEN ENDOCYCLIC AND EXOCYCLIC CLEAVAGE OF PYRANOSIDE ACETALS IS DEPENDENT UPON THE ANOMER, THE TEMPERATURE, THE AGLYCON GROUP,AND THE SOLVENT

Several cis-fused decalin pyranosides with intramolecular nucleophiles of high effective molarity were studied to determine the ratio betwee n endocyclic and exocyclic cleavage in specific-acid-catalyzed solvoly sis reactions. The molecular design that allows a differentiation betw een endo-or exocyclic cleavage is the symmetry and asymmetry of the re spective oxocarbenium ion intermediates. The synthesis of the molecula r probes involves eight steps from a known compound, and proceeds via a key intermediate functionalized with three different oxidation state s. A crystal structure confirmed the relative stereochemistry of the p robes. A quantifiable percentage of endocyclic cleavage for beta-pyran osides was found for all reaction conditions, whereas alpha-pyranoside s show exclusively exocyclic cleavage. The percent of endocyclic cleav age for beta-pyranosides is dependent upon the temperature, the aglyco n group, and the solvent. At lower temperatures endocyclic cleavage in creases. The Delta H-double dagger and Delta S-double dagger for endoc yclic and exocyclic cleavage were determined to be 19.2 +/- 1.4 kcal/m ol and -12.6 +/- 6.1 eu, and 22.8 +/- 1.1 kcal/mol and 3.7 +/- 3.8 eu in methanol, respectively. These values support the theory of stereoel ectronic control in the cleavage of pyranoside acetals. Pyranosides wi th phenyl aglycon groups exhibit significantly lower percentages of en docyclic cleavage than pyranosides with alkyl aglycon groups. Although an exact percentage of endocyclic cleavage of pyranosides in water co uld not be determined, it appears to be approximately the same or grea ter than that which occurs in methanol. The addition of non-hydrogen-b onding/non-nucleophilic solvents increased the percent of endocyclic c leavage. The results are interpreted to support some extent of nucleop hilic assistance in the endocyclic solvolysis of pyranosides, stereoel ectronic control on the site of cleavage, and the possibility of endoc yclic cleavage at the active site of glycosyl transfer enzymes.