Molecular design and synthesis of a planar telomestatin analogue

Abstract

Hypothetical macrocycles containing eight fused oxazole units would be logical planar analogues of telomestatin, but DFT calculations suggest the presence of excessive macrocyclic ring strain in such molecules that could complicate their synthesis and/or stability. We therefore designed a planar, C4-symmetric macrocycle composed of four oxazole and four thiazole units containing little or no ring strain. Cyclo(-ox-thia)4 (1) was successfully prepared from serine and cysteine in 19 steps to furnish the first example of an octa-azole macrocycle containing eight fused azole units.