The Synthesis and Biological Activity of "Crippled Biotin"

Article abstract of DOI:10.1071/CH9951907

(3aα,6β,6aα)-6-Methyltetrahydro-1H-thieno<3,4-b>pyrrol-2(3H)-one (2) was prepared as a crippled analogue of biotin.The key synthetic step involved hydrogenation of 6-methyl-1H-thieno<3,4-b>pyrrol-2(3H)-one on palladium to introduce the necessary all-cis configuration.Both compounds were weak inhibitors of the biotin-dependent wheat acetyl-CoA carboxylase compared to substrates or the potent herbicidal inhibitors of this enzyme, but were more potent than biotin or imidazolidone.Neither compound inhibited the biotin-dependent transcarboxylase component of bacterial acetyl-CoA carboxylase, nor did they significantly inhibit the growth of Arabidopsis thaliana.