BioChem - DOS

Nitrilase mediated mild hydrolysis of a carbon-14 nitrile for the radiosynthesis of 4-(7-hydroxycarbamoyl-[1-14 C-heptanoyl]-oxy)-benzoic acid methyl ester, [14 C]-SHP-141: A novel class I/II histone deacetylase (HDAC) inhibitor

Journal of labelled compounds & radiopharmaceuticals

Kitson, Sean L.; Watters, William; Moody, Thomas S.; Chappell, Todd; Mazitschek, Ralph

<P>A strategy has been developed for the carbon&#x2010;14 radiosynthesis of [<SUP>14</SUP>C]&#x2010;SHP&#x2010;141, a 4&#x2010;(7&#x2010;hydroxycarbamoyl&#x2010;heptanoyloxy)&#x2010;benzoic acid methyl ester derivative containing a terminal hydroxamic acid. The synthesis involved four radiochemical transformations. The key step in the radiosynthesis was the conversion of the 7&#x2010;[<SUP>14</SUP>C]&#x2010;cyano&#x2010;heptanoic acid benzyloxyamide [<SUP>14</SUP>C]&#x2010;4 directly into the carboxylic acid derivative, 7&#x2010;benzyloxycarbamoyl&#x2010;[<SUP>14</SUP>C]&#x2010;heptanoic acid [<SUP>14</SUP>C]&#x2010;8 using nitrilase&#x2010;113 biocatalyst. The final step involved deprotection of the benzyloxy group using catalytic hydrogenation to facilitate the release of the hydroxamic acid without cleaving the phenoxy ester. [<SUP>14</SUP>C]&#x2010;SHP&#x2010;141 was isolated with a radiochemical purity of 90% and a specific activity of 190 &mu;Ci/mg from four radiochemical steps starting from potassium [<SUP>14</SUP>C]&#x2010;cyanide in a radiochemical yield of 45%.</P>

2023

Wiley (John WileySons)

0362-4803

1099-1344

66

7

pp.172-179

10.1002/jlcr.4026

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART124972324