New metal-Catalyzed cyclization reactions of ortho-Alkynylsalicylaldehydes: total synthesis of (-) - Berkelic Acid

Abstract

The results related to the study of new cyclization reactions of ortho-alkynylsalicylaldehydes for the synthesis of complex heterocyclic compounds, as well as the application of these processes to the total synthesis of natural products are collected in this dissertation. Chapter one is dedicated to the synthesis of chromeno[2,3-b] pyrrole-carboxylate derivatives through a reaction between ortho-alkynylsalicylaldehydes and alkynylamines in the presence of gold catalysts. The reaction takes place through a novel cascade reaction that involves a double cycloisomerization/[4+2] cycloaddition process. This methodology has also been extended to the use of 3-butynol derivatives instead the alkynylamine derivatives. Also, a new silver triflate catalyzed reaction between ortho-alkynylsalicylaldehydes and 4-pentynols for the synthesis of spiro[furan-2,2¿-pyrano[2,3,4-de]chromene] derivatives has been developed. It is remarkable the the high stereoselectivity that these processes occur with. In Chapter 2, the application of the reaction between ortho-alkynylsalicylaldehydes and 4-pentynols (described in the previous chapter) to a new total synthesis of (-)-berkelic acid is described. The high modularity of this methodology has allowed the synthesis of a short library of analogues of the natural product. In the last part of this chapter, the biological activity studies developed with the natural product and some of the analogues synthetized are shown. Specifically, the antitumoral activity towards cancer cell lines OVCAR-3 and SSCC38 has been studied. In Chapter 3 it has been studied the reactivity of ortho-alkynylsalicylaldehydes and 4-pentynols with styrene derivatives that allows the construction of structurally different compounds depending of the catalysts and reaction conditions used. In the first place, in the presence of platinum catalysts, ortho-alkynylsalicylaldehydes and 4-pentynols provide 5,9-epoxybenzo[7]anulenne derivatives. On the other hand, benzo[de]chromenyl ketone derivatives are obtained when ortho-alkynylsalicylaldehydes and styrene derivatives are reacted in the presence of silver triflate and diphenylhydrogenphosphate.