Estudos visando a síntese da (-)-Pirenoforina através de uma metodologia de dimerização empregando a reação de Nozaki-Hiyama-Kishi

Abstract

Pirenophorin (1) belongs sixteen members’ ring lactones group, and in view of it structural and biological features, it was synthesized throughout literature in many times. In our synthetic strategy to reach this targed molecule were planning a dimerization methodology through Nozaki-Hiyama-Kishi reaction. The substrate to started this synthesis and pool chiral was the non-natural glutamic acid ((-)-122), to obtain after four steps and 29% yield (S)-1,4-pentanediol ((+)-126). It diol was protected with TIPSCl in 90% yield. To obtain a half-part of this target molecule was studied a coupling method between the diol protected and the acid-(E)-iodoacrilic through a esterification methodology. This acid was obtained by propargyl alcohol in two steps and 44% yield. The esterification transformation was testing by many ways and among them the Yamaguchi reaction. This experiment was carry-on by two methodologies: The classic one; and one-pot methodology. But both methodologies lead for a mixture of the product and Yamaguchi reagent derivative, in low yields. Then was made some theoretical studies for obtain the LUMOs’ energy and orbital shapes of mixed anhydride. From this study was possible notice that both carbonyl groups have a LUMOs’ input. Hence was possible to confirm the experimental result. In view that Yamaguchi reactions’ does not worked, that ester half part were get through Mitsunobu reaction in 80% yield. After reach the half-part the ester intermediate pass through a deprotection and oxidation reactions to than being obtain the aldehyde 125 (77% yield, two steps), to Nozaki-Hiyama-Kishi coupling. This reaction was carry-on and then the final product was obtained and confirmed by literature data.