Catálogo de Investigaciones 2017-2018

CATÁLOGO DE INVESTIGACIONES | AÑO ACADÉMICO 2017-2018 51 Development of a One-Step methodology for the Synthesis Allylic Alcohols Based on the Hydrometalation and Carbometalation of Propargylic Alcohols Followed by the Epoxide Cleavage to Obtain Polyketide Fragments Precursors In this study we have proposed the following aims: 1) the development of a one-step procedure for the synthesis of allylic alcohols as key intermediates by cleaving epoxides with alkenyl alanates and Grignard derivatives and 2) determine the scope and limitation of our allylic alcohols to the construction of polyketide chains in natural products. For the synthesis of cis and trans allylic alcohols we have explored several experiments using diisobutylaluminum hydride (DIBAH) as a key reagent to promote the hydrometalations followed by the cleavage of the propylene oxide. The results suggest that the use of propargyl alcohols as starting material instead of aliphatic alkynes is problematic and produced undesired products. Aliphatic alkynes work very well and highs yields were obtained. Likewise, we exposed the propargylic alcohols to carbometalations using Grignard and alkenyl aluminum reagents to afford E and Z allylic alcohols, followed by the epoxide cleavage. Preliminary results show impressive high yields on all products. Specifically, we have explored the Zr-catalyzed methyl aluminum reaction followed by the cleavage of propylene oxide to obtain E-allylic alcohols. In addition, the complementary and novel reaction of the copper catalyzed oxygenated alkenyl intermediate to cleavage of several terminal epoxides to obtain complementary Z-allylic alcohols has been explored. Full characterization of these products by NMR are in process. In conclusion, these procedures will demonstrate the utility of our new methodology of epoxide cleavage mediated by oxygenated alkenyl alanate and Grignard reagents for the enantio and regioselective construction of polyketide fragments. In addition, this will extend the applicability of our methodology for the synthesis of polyketides and present possible opportunities to increase or modify the biological and therapeutic activity. This research will lead to improved access to a wide new range of natural products and their derivatives. josé martínez matías annual biomedical research conference for minority students mentor: dr. raúl r. rodríguez berrios poolyketides allylic alcohols epoxides hydrometallation carbometallation