| Popis: |
The oximidines are characterized by a benzo-fused macrolactone bearing an N-acylated enamine side chain, and are among a family of natural products known as benzolactone enamides. Nearly all the members of this family exhibit potent antitumor activity. One particular family, the oximidines, showed selective inhibition of mammalian vacuolar-type proton ATPase. In this thesis, a regio- and stereoselective approach to the macrolactone ring system of the oximidines is described. This approach is based on the ring-closing metathesis as a key reaction. The successful application of this reaction in the present context provided an exceptionally efficient and direct entry into the structurally and biologically interesting class of cytotoxic natural product. Based on this strategy, a regio- and stereoselective synthesis of the fully functionalized oximidine I core structure was achieved. Efforts towards the asymmetric total synthesis of oximidine I and II will be described. |
