Deracemization of secondary alcohols by stereoinversion and reduction of methylene ketones by microorganisms

Author(s)

Tarcila Cazetta

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2014-10-10

Examining board members

José Augusto Rosário Rodrigues; Ronaldo Aloise Pilli; Paulo Mitsuo Imamura; Cintia Duarte de Freitas Milagre; Andre Luiz Meleiro Porto

• Advisor: José Augusto Rosário Rodrigues

Abstract

In this research project were studied methodologies aimed at the preparation of chiral molecules using microorganisms. In Chapter 1, yeast and fungi were used for the preparation of enantiomerically pure alcohols and diols by kinetic resolution oxidative and desracemização by estereoinversão. The alcohol (R)-1-(3-hydroxyphenyl)ethanol, a precursor in the preparation of Rivastigmine, a drug used in the treatment of Alzheimer's disease was obtained by a process of highly efficient kinetic resolution and its absolute configuration was determined by using the technique of circular dichroism. The (R)-1-(3-pyridinyl)ethanol was obtained by desracemization mediated by fungus Geotrichum candidum. The reaction mechanism was studied using pure enantiomers as starting substrate material, so that it was possible to establish a mechanism for desracemização. The diol (S)-1-phenyl-1,2-ethanediol was prepared by a process of highly efficient estereoinversão by the yeast Candida albicans. The reaction mechanism has been studied, as well as the influence of donating and electron-withdrawing groups attached to the aromatic ring. It has been found that the nature of the group may dramatically influence of the steps of desracemization. In Chapter 2, reduction C=C bonds reactions were studied by the action of enoate-reductase enzymes from yeast Pichia kluyveri. Methyleneketones were prepared and the microorganism caused a reduction of the C=C bond chemotherapy and stereoselective manner, such that the carbonyl group of the ketone remained intact. Chiral ?-methyl ketones were obtained with excellent yields and enantiomeric excesses. In particular, (S)-2-methyl-1-phenylhexan-1-one, a hitherto not reported in literature compound was prepared in excellent yield (93%) and ee (99%) and its absolute configuration was determined using the technique of circular dichroism (AU)