A new method for steroid synthesis is proposed. The key element in this procedure is the development of a means to direct the course of ring formation in the cyclization of a polyolefin. To accomplish this, transition metal clusters are proposed as cyclization templates to chemically mimic the enzyme function which formally allows a polyolefin to cyclize, in vivo, through a secondary as opposed to a tertiary cationic center. The latter pathway is favored in the non-enzymatic cyclization of polyolefins. The development of such an enzyme mimic will proceed in stepwise fashion from that of a template designed to direct monocyclic product formation from a diene to that of a template which directs formation of the entire steriod nucleus from a polyolefin in a one-step cyclization process. The requirements for a transition metallic enzyme mimic are discussed, and various metal clusters are suggested to fill this role. For the mono- and bicyclic product cases, synthesis of polyolefin substrates is outlined. Approaches to complexation of a specific polyolefin with a given metal cluster and cyclization of the metal-complexed polyolefin are discussed. Plans for studies in the tri- and tetracyclic cases are outlined. Information to be gained concerning the nature of reactivity of metal-coordinated olefins is an important footnote to these studies.
NIH ExPorter
NIH ExPorter