Synthesis and ring contraction reactions of polyazamacrolides

The synthesis of three analogues of the single most abundant component of a ladybird beetle (Epilachna borealis) defensive secretion, the trimeric 42- membered polyazamacrolide PAML 681, is described. Construction of the nonna tural macrocyclic trimers began with the preparation of the corresponding m onomeric segments, followed by their oligomerization and a final macrolacto nization step of the activated linear trimeric hydroxy acid. The relative r ates of the O-to-N acyl migrations that are characteristic of PAML 681 itse lf, as well as of the synthetic analogues, were investigated. These studies showed that changes in the substitution pattern adjacent to the nucleophil ic nitrogen atom, along with changes in the size of the oxaazacyclic interm ediates, have substantial effects on the polyazamacrolide rearrangement rat es.