Enantioselective syntheses of aldohexoses using macrocyclic stereocontrol
Abstract
A general method for enantioselective syntheses of aldohexoses using macrocyclic stereocontrol is described. The strategy employs simultaneous bis-dihydroxylation of chiral macrocyclic dienes to install the four contiguous stereogenic centers of aldohexoses. Conformational searches have been performed on two different macrocyclic precursors to the desired aldohexose using molecular mechanics calculations. Qualitative analysis of the low energy conformers obtained from these searches predicts L-gulose and D-idose, respectively, to be formed as major products in high enantiomeric ratios. The synthesis of the macrocyclic precursor to L-gulose was carried out in 5 steps from l-menthol. Key steps in this synthesis include a one-pot oxidation-Baeyer Villiger rearrangement of l-menthol and an intramolecular Horner-Wadsworth olefination to form a 14-membered ring in high yield. A broad survey of dihydroxylation conditions for osmylation of the diene was conducted. Although the majority of conditions resulted in complex mixtures of diastereomeric tetraols, catalytic OsO$\sb4$ and Me$\sb3$NO afforded two diastereomeric tetraols cleanly. Enantiomeric purity of the dihydroxylation products was determined through conversion of the macrocyclic tetraol to the corresponding hexitol hexaacetate and correlation with authentic material. The generality of this method was demonstrated by the synthesis of D-galactose from a related macrocycle using identical osmylation conditions.
Degree
Ph.D.
Advisors
Lipton, Purdue University.
Subject Area
Organic chemistry
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