Studies in asymmetric synthesis: Diastereoselective manipulation of chromatographically resolved pyranosides for the syntheses of natural products.
AuthorArterburn, Jeffrey Burton.
AdvisorMash, Eugene A.
MetadataShow full item record
PublisherThe University of Arizona.
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AbstractChromatographic resolution of diastereomeric pyranosides prepared from enantiomerically pure α-hydroxy esters was shown to be a reliable method of obtaining a variety of potentially useful chiral substrates. Several enantiomerically pure α-hydroxy esters are commercially available and lead to chromatographically separable pyranosides. The methyl esters of lactic and mandelic acid are inexpensive, available in both enantiomeric forms, and were easily incorporated into readily available racemic pyran substrates. The resolutions were performed on a preparative scale using gravity driven silica gel column chromatography. Phenylselenyl substituted tetrahydropyranosides were prepared using the alkoxy-selenation reaction and were subjected to elimination under mild oxidative conditions to afford dihydropyranosides. The resolved chirality of the anomeric center permitted diastereoselective functionalization of the alkene moiety in these compounds. The dihydropyranosides possessing lactate or mandelate ester appendages preferentially underwent epoxidation with peroxy acids and cis-dihydroxylation with catalytic osmium tetroxide on the face of the alkene anti to the appendage. Reduction of the ester with lithium aluminum hydride converted the sterically demanding ester appendage into a polar primary alcohol. This enabled the appendage to participate in the delivery of electrophilic reagents such as peroxy acids and mercuric acetate preferentially to the syn-face of the dihydropyranoside alkene. Utilization of these general principles permitted the asymmetric syntheses of 4-deoxyribose, (R)-mevalonolactone, a protected mevinic acid precursor, and the calicheamicin ethylamino sugar.