BioChem - DOS

Chemoenzymatic synthesis of (S)-Pindolol using lipases

Applied catalysis. A, General

Lima, Gledson Vieira; da Silva, Marcos Reinaldo; de Sousa Fonseca, Thiago; de Lima, Leandro Bezerra; de Oliveira, Maria da Conceiç ã o Ferreira; de Lemos, Telma Leda Gomes; Zampieri, Davila; dos Santos, Jose Cleiton Sousa; Rios, Nathalia Saraiva; Gonç alves, Luciana Rocha Barros; Molinari, Francesco; de Mattos, Marcos Carlos

<P><B>Abstract</B></P> <P>A straightforward chemoenzymatic synthesis of (<I>S</I>)-Pindolol has been developed. The key step involved the enzymatic kinetic resolution of <I>rac-</I>2-acetoxy-1-(1<I>H</I>-indol-4-yloxy)-3-chloropropane with lipase from <I>Pseudomonas fluorescens</I> via hydrolytic process to obtain enantiomerically enriched halohydrin <I>(</I>2<I>S</I>)-1-(1<I>H</I>-indol-4-yloxy)-3-chloro-2-propanol (96% <I>ee</I>) and (2<I>R</I>)-2-acetoxy-1-(1<I>H</I>-indol-4-yloxy)-3-chloropropane (97% <I>ee</I>). The latter was subjected to a hydrolysis reaction catalyzed by <I>Candida rugosa</I> leading to <I>(</I>2<I>R</I>)-1-(1<I>H</I>-indol-4-yloxy)-3-chloro-2-propanol (97% <I>ee</I>), followed by a reaction with isopropylamine, producing (<I>S</I>)-Pindolol (97% <I>ee</I>) in quantitative yield.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A straightforward chemoenzymatic synthesis of (<I>S</I>)-Pindolol has been developed. </LI> <LI> The key step involved kinetic lipase-mediated resolution of a haloydrin acetate via hydrolytic process. </LI> <LI> <I>P. fluorescens</I> was a robust biocatalyst and afforded the halohydrin acetate as chiral intermediate with 97% ee. </LI> <LI> The use of THF as co-solvent was essential for a high enantioselectivity kinetic resolution process (E>200). </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

2017

Elsevier

0926-860x

1873-3875

546

pp.7-14

10.1016/j.apcata.2017.08.003

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART78538899

https://air.unimi.it/bitstream/2434/546231/5/Manuscript%20Pindolol.pdf

Pindolol; Lipases; Biocatalysis; Chemoenzymatic synthesis; Enzymatic kinetic resolution; Pseudomonas fluorescens