STEREOCHEMICAL CONTROLLED SYNTHESIS OF BIOLOGICALLY ACTIVE AMINES

University Of Puerto Rico At Humacao, Humacao PR

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Abstract

New technology for the preparation of chiral compounds in organic chemistry is an area of intense developments, due to the concern that many chiral drugs are consumed as racemic mixtures with the potential toxic effects caused by the other enantiomer. Chiral amines, amino alcohols and amino acids are important organic compounds used as building blocks for the synthesis of many pharmaceutical products, and auxiliaries in a variety of enantioselective organic preparations. The design of new methodologies for the enantioselective synthesis of enantiopure compounds with biological activity will be the main purpose of this project. Through our previous research work, we have developed new procedures for primary phenylalkylamine synthesis with modest to good optical purity via the reduction of N-substituted organometallic imino derivatives using known chiral organoborane reagents. Presently, we envision the application of the developed methodology for the preparation of amines and amino alcohols. Besides, the synthesis of novel chiral aminoborohydrides generated by the alpha deprotonation of chiral amine-borane complexes with n-BuLi or LDA for the reduction of imine and/or carbonyl groups, will be proposed. These reagents offer higher reactivity and a better stereochemical control since other competing reducing species are not present. Representative pro-chiral imines and aromatic ketoimines will be reduced with the proposed chiral agents and their enantioselectivity studied under various reaction conditions. Based on the results of the alpha-alkylation of O-TBS acetophenone oximes, asymmetric induction for the preparation of non- racemic products will be attempted using chiral amides as bases, or chiral catalysts, such as 1,3,2-oxazaborolidines. The chiral deprotonation of racemic primary amines with acidic alpha-protons at benzylic positions and amino acids, will be studied since this new area offer great value for the preparation of biological active compounds. The proposed synthetic strategies will be focused on the development of new methods for the preparations of homochiral compounds used as intermediaries of reagents for the synthesis of important pharmacological products.