Date of Graduation
2006
Document Type
Dissertation/Thesis
Abstract
De novo asymmetric synthesis is a strategy that uses asymmetric catalysis to construct chiral molecules from achiral starting materials. One of the advantages of this strategy is that we can synthesize numerous stereoisomers (e.g. the enantiomers) of the target natural product for biological testing. Substituted α,β-unsaturated δ-lactones are an important class of natural products with a wide range of biological activity. Many synthetic methodologies have been developed to synthesize this core structure. However, they depended on either performing kinetic resolutions or chiral starting materials (e.g. carbohydrates). We envisioned using catalytic asymmetric catalysis (de novo approach) to synthesize these complex molecules. Thus, a flexible, enantioselective approach was developed to synthesize phomopsolide D, phomopsolide E and their analogs. This approach relied on the application of the Noyori asymmetric hydrogenation of furyl ketone to produce the secondary furyl alcohol in high enantioexcess which could be stereoselectively transformed into α,β-unsaturated δ-lactones by a short, highly diastereoselective oxidation and reduction sequence. Natural products containing the syn-1,3-diol moiety are also an important class of compounds with a wide range of biological activities. Although numerous strategies have been developed to synthesize the syn-1,3-diol structural motif, there still exists a need for a more efficient asymmetric catalysis approach to these complex molecules. In particular, we used an asymmetric hydration (de novo) approach to these important targets. In this asymmetric hydration approach, an asymmetric oxidation/reduction protocol was applied to dienoates to afford the desired δ-hydroxy enoates. The alcohols were then diastereoselectively converted into benzylidene-protected syn-3,5-dihydroxy carboxylic esters in good yield and excellent selectivities. This asymmetric hydration approach was applied to the syntheses of milbemycin β 3 and apicularen A.
Recommended Citation
Li, Miaosheng, "De novo asymmetric syntheses of biologically important natural products: Phomopsolide D, phomopsolide E, milbemycin beta3 and apicularen A." (2006). Graduate Theses, Dissertations, and Problem Reports. 9290.
https://researchrepository.wvu.edu/etd/9290