Enantioselective synthesis of iminosugars and hexoses from furfural

Aminoglycosides and iminosugars are natural products with important biological activities. One of our goals as synthetic organic chemists is to develop efficient routes to these type of natural products. We envisioned using catalytic asymmetric catalysis to synthesize these complex molecules.; An early development in the O'Doherty research group was the development of a practical and efficient route to various D- or L-carbohydrate derivatives from furan diols using the Sharpless dihydroxylation on vinylfuran to establish the absolute stereochemistry. The resulting diols are produced in high enantiomeric excess and can be stereoselectively transformed into differentially protected D- or L-carbohydrates via highly enantioselective and diastereoselective oxidation and reduction sequences.; The versatility of this approach was tested by studying the asymmetric aminohydroxylation. Its use has enabled the conversion of a simple achiral precursor into more complex chiral aminoalcohols. Furfural was converted to vinylfuran, which then undergoes stereochemical induction by asymmetric aminohydroxylation. Two regioisomeric aminoalcohols were formed in the reaction and factors affecting the regioselectivity and enantioselectivity were studies.; Alternative and more efficient routes to each aminoalcohol regioisomer were developed. Asymmetry was achieved by use of a Sharpless asymmetric dihydroxylation and a Noyori asymmetric ketone reduction. Each regioisomer was synthesized in greater than 95% enantiomeric excess by these improved synthetic routes.; These aminoalcohols were converted into several isomers of deoxy-iminosugars, aminosugars, and deoxy-aminosugars, including 6-aminomannose, 6-aminogulose, and 1-deoxymannojirimycin. Each may be obtained in either enantiomer by selecting the appropriate chiral ligand for the osmium catalyzed dihydroxylation or ruthenium-catalyzed ketone reduction. All sugars and iminosugars were synthesized in good overall yields from furfural. This methodology illustrates the utility of the asymmetric catalysis for the enantioselective synthesis of natural products and theirs analogs.