Stereoselective Access to 1-[2-Bromo(het)aryloxy]propan-2-amines Using Transaminases and Lipases; Development of a Chemoenzymatic Strategy Toward a Levofloxacin Precursor.
Two independent enzymatic strategies have been developed toward the synthesis of enantioenriched 1-[2-bromo(het)aryloxy]propan-2-amines. With that purpose a series of racemic amines and prochiral ketones have been synthesized from commercially available 2-bromophenols or brominated pyridine derivatives bearing different pattern substitutions in the aromatic ring. Biotransamination experiments have been studied using ketones as starting materials, yielding both the (R)- and (S)-amine enantiomers with high selectivity (91-99% ee) depending on the transaminase source. In a complementary approach, the classical kinetic resolutions of the racemic amines have been investigated using Candida antarctica lipase type B as biocatalyst. Ethyl methoxyacetate was found as a suitable acyl donor leading to the corresponding (S)-amines (90-99% ee) and (R)-amides (88-99% ee) with high selectivity in most of the cases. A preparative biotransamination process has been developed for the synthesis of (2S)-1-(6-bromo-2,3-difluorophenoxy)propan-2-amine in 61% isolated yield after 24 h, a valuable precursor of the antimicrobial agent Levofloxacin.
Organic and Inorganic Chemistry Department, Biotechnology Institute of Asturias (IUBA), University of Oviedo , Avenida Julián Clavería s/n, 33006 Oviedo, Spain.
Ángela
Á
Mourelle-Insua
Organic and Inorganic Chemistry Department, Biotechnology Institute of Asturias (IUBA), University of Oviedo , Avenida Julián Clavería s/n, 33006 Oviedo, Spain.
María
M
López-Iglesias
Organic and Inorganic Chemistry Department, Biotechnology Institute of Asturias (IUBA), University of Oviedo , Avenida Julián Clavería s/n, 33006 Oviedo, Spain.
Vicente
V
Gotor
Organic and Inorganic Chemistry Department, Biotechnology Institute of Asturias (IUBA), University of Oviedo , Avenida Julián Clavería s/n, 33006 Oviedo, Spain.
Vicente
V
Gotor-Fernández