Enzyme inhibitors, synthesis and approach to mechanism
Synthetic approach toward channel protein inhibitors (tetrodotoxin, ciguatoxin) and protein phosphatase inhibitors (tautomycin) is discussed with special reference to the stereochemical control. Stereochemical control in organic synthesis is the major interest in the industrial production as well as in the basic studies directed to understand the nature of organic molecules. A-strain has been discussed since Johnson's substituted exo-olefin of the cyclohexane system was reported in 1965. This concept was expanded to an acyclic case as illustrated in Fig. 1, in which the most stable conformer is the one with the least bulky substituent (€3) in the plane of the olefin. One face of this plane contains an oxygen atom, that acts as an anchor for metal chelation, while the other is activated by the inherent polarization of the C-0 bond. In this paper, both the cyclic and acyclic cases are discussed.