Research Projects

The phomopsene diterpenes and cyclopiane diterpenes are two structurally related families of natural products that contain a tetra cyclic core A and B (Figure 1, see attached research proposal). Interestingly, a 1,3-shift of the C-C bond from C4 to C6 in tetra cycle A of phomopsene diterpenes produces a tetracyclic framework B that constitutes a basic skeleton of the structurally related cyclopiane diterpenes. The phomopsene diterpenes isolated from plant pathogenic fungus Phomopsis amygdali, belong to a unique class of 5/5/6/5 polycyclic diterpenes. On the other hand, isolated from the penicillium Genus, the structurally related cyclopiane diterpenes are a group of fascinating natural products such as conidiogenone, conidiogenol, and conigenone B-F, characterized by the presence of complex and synthetically challenging highly fused 6/5/5/5 tetracyclic frameworks, but they differ in their level of oxygenation with diverse functionality. In the continuation of ongoing work in our laboratory, we became interested in the asymmetric synthesis of structurally related challenging phomopsene family of diterpenes, as well as the family of cyclopiane diterpene natural products (conidiogenone, conidiogenol, conidiogenone B, conidiogenone C and conidiogenone F) using a unified and flexible approach. Our proposed unified strategy towards both families of target natural products is derived from our ongoing studies on conidiogenone B (6) (3rd target from cyclopiane diterpene family, see attached research proposal), with the central strained ring (highlighted in green) being a focal point of disconnection. Specifically, we view that the diastereoselective radical cyclization of suitable tricycles will offer a regio and stereo chemically flexible approach to both tetra cyclic cores, from which both families of phomopsene and cyclopiane diterpenes will be synthesized via functional group interconversions. Both tricycles required for phomopsene diterpenes and cyclopiane diterpenes, conveniently derive from the common enone intermediate (Hajosh-Parrish analogue). (For full details, please see attached full research proposal)