Experimental Lineage and Functional Analysis of a Remotely Directed Peptide Epoxidation Catalyst

We describe mechanistic investigations of a catalyst (1) that leads to selective epoxidation of farnesol at the 6,7-position, remote from the hydroxyl directing group. The experimental lineage of peptide 1 and a number of resin-bound peptide analogues were examined to reveal the importance of four N-terminal residues. We examined the selectivity of truncated analogues to find that a trimer is sufficient to furnish the remote selectivity. Both 1D and 2D ¹H NMR studies were used to determine possible catalyst conformations, culminating in proposed models showing possible interactions of farnesol with a protected Thr side chain and backbone NH. The models were used to rationalize the selectivity of a modified catalyst (17) for the 6,7-position relative to an ether moiety in two related substrates.