Synthesis of natural products on solid phases via copper-mediated coupling: Synthesis of the aristogin family, spiraformin a, and hernandial

Article abstract of DOI:10.1002/ejoc.200900632

The formation of natural products on solid phases via diaryl ether coupling is presented herein, Starting with either commercially-available or easily-producible benzoic, cinnamic, or propionic acids, all immobilized on Merrifield resin, via a. pentane linker, copper-mediated couplings yielded solid phase diaryl ethers in good yields. Both, phenol and resins containing aryl halides were used for these Ullmann-type couplings to generate resin-bound natural product derivatives, Through cleavage from the resin, eight naturally occurring substances isolated from Aristolochia elegans, Hernandia nymphaeifolia, Spiraea iormosana, and Kandelia candel were prepared. To the best of our knowledge, four of these compounds, namely Aristogin D and F as well as Spiraformin A. and compound 12 have never previously been synthesized, Gaining access to these natural products on solid supports, demonstrated the utility of diaryl ether formation for the development of combinatorial syntheses, Our approach to diaryl ethers on solid support offers the possibility of synthesizing libraries of natural product derivatives via combinatorial syntheses,