The Synthesis of Bicyclic Piperazinone and Related Derivatives
We have been examining synthetic approaches to conformationally restricted peptide building blocks that would allow for the construction of a variety of possible structures in a straight-forward, general way ( 1 ). To date, this effort has focused on developing the chemistry needed to rapidly imbed sections of a peptide backbone into a bicyclic or polycyclic ring skeleton ( 2 – 4 ). Such a transformation is accomplished by replacing spacially close hydrogens in a desired conformation with an appropriately sized carbon bridge. The potential advantages of this approach include the preservation of both the peptide backbone and the side chains in the analog, the ability to control the orientation of the side chains relative to each other, the increased hydrolytic stability of the analog, and the ease with which new analogs can be designed. The potential disadvantages of this approach include the difficulty associated with synthesizing the analogs and the steric size of the bridges added. In this chapter, a convenient preparation of analogs having the general structure of I (Fig. 1 ) is described. Figure 1