| An important class of carbohydrate analogs is the iminosugars, molecules where the endocyclic oxygen atom is replaced with a nitrogen atom. This class of compounds has been found to act as glycosidase inhibitors allowing for the use of these molecules in the study of glycoprotein processing enzymes. The iminosugars have also been found to possess a wide range of biological activities such as anti-cancer, anti-HIV and against viral infections. While several routes exist for the synthesis of iminosugars, most rely on the use of chiral starting materials. We were interested in the use of asymmetric catalysis for synthesizing these molecules.; Our route relies on the use of asymmetric palladium chemistry to set the initial stereocenter, which is then used to set the remaining stereocenters. The other key step in the synthesis is the use of ring closing metathesis. Utilizing this chemistry we were able to synthesize protected 1,2-dideoxy and 1-deoxyiminosugars.; The 1,3-syn-diol motif is a common structural unit found in several classes of natural products with a wide range of pharmacological activities. A class of these active molecules is the 6-substituted 5,6-dihydropyran-2-ones. These molecules have been isolated from plant extracts that have shown biological activity against tuberculosis, selective COX-1/COX-2 inhibitory activity, antibacterial properties, and antifungal activity. Nothing is known about the mode of action for these compounds, or the role of stereochemistry in their activities. Thus we wanted to develop a route toward these molecules which would allow for the synthesis of the natural compounds as well as analogs for biological testing.; We first developed a methodology for synthesizing 1,3-syn-diols utilizing cross metathesis between homoallylic alcohols and acrylates, followed by conjugate addition with benzaldehyde and base. The route is straightforward and can be used iteratively for the synthesis of poly 1,3-syn-diols.; The chemistry was then applied toward the synthesis of several of these natural products. This route was used in the enantioselective synthesis of cryptocarya triacetate, cryptocaryolone, and cryptocaryolone diacetate, along with the corresponding 5,7-bis-epi diastereomers. This methodology was also used iteratively for the racemic synthesis of passifloricin A and the δ-lactone of (2Z, 5S, 7S, 9R, 11R)-tetrahydroxyhexacos-2-enoic acid. |
