Solid phase combinatorial synthesis of a library of macro-heterocycles and related acyclic compounds.

A solid phase synthesis of macrolactones from three building blocks and in eight steps is described. The synthesis which is carried out on the DHP resin includes Mitsunobu and DIC couplings. The macrocyclization occurs by SN2 displacement of an allylic chloride by a malonate anion. The synthetic methodology is suitable for the synthesis of arrays of macrocycles as well as linear compounds.