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.

本研究针对催化剂（1）开展了机理探究，该催化剂可使法尼醇在远离羟基导向基团的6,7位发生选择性环氧化反应。我们对肽1以及多款树脂结合肽类似物的实验制备谱系进行了考察，揭示了其N端四个残基的关键作用。我们进一步测试了截短型类似物的选择性，发现仅需三肽片段即可实现该远程选择性。我们通过一维和二维质子核磁共振（¹H NMR）研究解析了催化剂可能的构象，最终构建出可体现法尼醇与保护型苏氨酸侧链及主链NH之间潜在相互作用的模型。所构建的模型可用于阐释修饰型催化剂（17）在两种相关底物中，相较于醚基片段更倾向于在6,7位发生反应的选择性机制。