The Synthesis and Biological Activity of 'Crippled Biotin'

Abstract

(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.