New Methodologies for the Synthesis of Biologically Active Amino Derivatives

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The preparation of chiral compounds in organic chemistry is an area of intense study due to the concern that many chiral drugs are consumed as racemic mixtures with the potential toxic side effects caused by the other enantiomer. In addition, chiral organic compounds are used as building blocks for the synthesis of many pharmaceutical products, and as auxiliaries in a vadety of enantioselective organic preparations. The main purpose of this project is to design new methodologies for the enantioselective synthesis of biological active compounds. Based on the expertise developed during the past years, work on the synthesis of enantio-pure primary phenylalkyl amines, and other amino derivatives v/a the reduction and alkylation of N-substituted organometallic (boron and silicon) imino derivatives will be our main objectives. We will continue with a detailed investigation of the scope and mechanisms involved in the achiral and enantioselective reductions of these synthons, since in addition to the development of primary amines, novel methodologies have been discovered for other important pharmaceutical compounds, such as hydroxyl amines and benzazepines. Preliminary resultson the synthesis of novel chiral aminoborohydrides and organoboranes reagents generated by the reaction of 1,3,2-oxazaborolidines with organolithiums, will be expanded for the enantioselective reduction of imine and/or carbonyl groups. These reagents offer a great potential for a variety of biomedical applications. The chemistry of O-silylated and O-borylated aromatic ketoximes will be further investigated for the synthesis of biological active heterocyclic amino compound and other dedvatives. In addition, based on the results of the o¿-alkylation and silylation of O-silylated oximes, we will explore the novel synthesis of 1,2- and 1,3-amino alcohols. The proposed synthetic strategies will be focused on the development of new methods for the preparation of homochiral compounds used as intermediaries or reagents for the synthesis of important pharmacological products.