BioChem - DOS

Enzymatic Preparation of an (S)-Amino Acid from a Racemic Amino Acid

Organic process research & development

Chen, Yijun; Goldberg, Steven L.; Hanson, Ronald L.; Parker, William L.; Gill, Iqbal; Tully, Thomas P.; Montana, Michael A.; Goswami, Animesh; Patel, Ramesh N.

<P>The (<I>S</I>)-amino acid, (<I>S</I>)-2-amino-3-(6-<I>o</I>-tolylpyridin-3-yl)propanoic acid (<B>3</B>), is a key intermediate needed for synthesis of an antidiabetic drug candidate. Three enzymatic routes to <B>3</B> were explored. (<I>S</I>)-Amino acid <B>3</B> could be prepared in 73% isolated yield with 99.9% ee from racemic amino acid <B>1</B> using (<I>R</I>)-amino acid oxidase from <named-content content-type='genus-species'>Trigonopsis variabilis</named-content> expressed in <named-content content-type='genus-species'>Escherichia coli</named-content> in combination with an (<I>S</I>)-aminotransferase using (<I>S</I>)-aspartate as amino donor. The (<I>S</I>)-aminotransferase was purified from a soil organism identified as <named-content content-type='genus-species'>Burkholderia</named-content> sp. and cloned and expressed in <named-content content-type='genus-species'>E. coli</named-content>. (<I>S</I>)-Amino acid <B>3</B> with 100% ee was also prepared in 68% solution yield and 54% isolated yield from <B>1</B> using recombinant (<I>R</I>)-amino acid oxidase from <named-content content-type='genus-species'>T. variabilis</named-content> and an (<I>S</I>)-amino acid dehydrogenase from <named-content content-type='genus-species'>Sporosarcina ureae</named-content>. The cofactor NADH required for the reductive amination reaction was regenerated using formate and formate dehydrogenase. The chemoenzymatic dynamic resolution of <B>1</B> by (<I>R</I>)-selective oxidation with Celite-immobilized (<I>R</I>)-amino acid oxidase in combination with chemical imine reduction using borane&minus;ammonia complex gave an 81% solution yield and 68% isolated yield of <B>3</B> with 100% ee.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/oprdfk/2011/oprdfk.2011.15.issue-1/op1001534/production/images/medium/op-2010-001534_0001.gif'></P>

2011

American Chemical Society

1083-6160

1520-586x

15

1

pp.241-248

10.1021/op1001534

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART55278961