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[摘要]：1,4-anhydro-4-thio-D-arabinitol, analogs of the naturally occurring glycosidase inhibitor salacinol I and II, are described. These compds. were designed on the basis of the structure activity data of chain-extended analogs of salacinol, with the intention of detg. the hitherto unknown stereochem. structure of kotalanol, the naturally occurring seven-carbon chain-extended analog of salacinol. The target zwitterionic compds. were synthesized by means of nucleophilic attack of the PMB-protected 1,4-anhydro-4-thio-D-arabinitols at the least hindered carbon atom of two 1,3-cyclic sulfates differing in stereochem. at only one stereogenic center. The desired cyclic sulfates were synthesized starting from D-glucose via Wittig olefination and Sharpless asym. dihydroxylation. Deprotection of the coupled products by using a two-step sequence afforded two sulfonium sulfates. Optical rotation data for II indicated a correspondence with that reported for kotalanol. However, comparison of 1H and 13C NMR spectral data of I and II with those of kotalanol indicated discrepancies. The collective data from this and published work were used to propose a tentative structure for the naturally occurring compd., kotalanol. Comparison of phys. data of previously synthesized analogs with those for the recently isolated six-carbon chain analog, salacinol or reticulanol, also led to elucidation of this structure. Interestingly, both I and II inhibited recombinant human maltase glucoamylase (MGA), as expected from previous structure activity studies of lower homologues, with Ki values of 0.13 ?0.02 and 0.10 ?0.02 mM. |
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