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Stereoselective Access to 1-[2-Bromo(het)aryloxy]propan-2-amines Using Transaminases and Lipases; Development of a Chemoenzymatic Strategy Toward a Levofloxacin Precursor

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논문

Stereoselective Access to 1-[2-Bromo(het)aryloxy]propan-2-amines Using Transaminases and Lipases; Development of a Chemoenzymatic Strategy Toward a Levofloxacin Precursor

학술지

Journal of organic chemistry

저자명

Mourelle-Insua, Á ngela; Ló pez-Iglesias, Marí a; Gotor, Vicente; Gotor-Ferná ndez, Vicente

초록

<P>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 (<I>R</I>)- and (<I>S</I>)-amine enantiomers with high selectivity (91&ndash;99% <I>ee</I>) depending on the transaminase source. In a complementary approach, the classical kinetic resolutions of the racemic amines have been investigated using <I>Candida antarctica</I> lipase type B as biocatalyst. Ethyl methoxyacetate was found as a suitable acyl donor leading to the corresponding (<I>S</I>)-amines (90&ndash;99% <I>ee</I>) and (<I>R</I>)-amides (88&ndash;99% <I>ee</I>) with high selectivity in most of the cases. A preparative biotransamination process has been developed for the synthesis of (2<I>S</I>)-1-(6-bromo-2,3-difluorophenoxy)propan-2-amine in 61% isolated yield after 24 h, a valuable precursor of the antimicrobial agent Levofloxacin.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/joceah/2016/joceah.2016.81.issue-20/acs.joc.6b01828/production/images/medium/jo-2016-01828w_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jo6b01828'>ACS Electronic Supporting Info</A></P>

발행연도

2016

발행기관

American Chemical Society

라이선스

cc-by-nc-nd

ISSN

0022-3263

ISSN

1520-6904

81

20

페이지

pp.9765-9774

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논문; 2016-10-07

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