Botulinum neurotoxins synthesis

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Oost, T., Sukonpan, C., Brewer, M., Goodnough, M., Tepp, W., Johnson, E.A., and Rich, D.H. 2003. Design and synthesis of substrate-based inhibitors of botulinum neurotoxin type B metaUoprotease. Biopolymers 71 602-619. 

Pang, Y.P., Vummenthala, A., Mishra, R.K., Park, J.G., Wang, S., Davis, J., Millard, C.B., and Schmidt, J.J. (2009) Potent new small-molecule inhibitor of botulinum neurotoxin serotype A endopeptidase developed by synthesis-based computer-aided molecular design. PLoS One, 4, e7730. 

SCHEME 5 Synthesis of an inhibitor of botulinum neurotoxin via oxidative aryiation. 

Li and colleagues took advantage of the Cadogan-Sundberg indole synthesis to prepare botulinum neurotoxin A light chain (BoNT/A LC)... 

DeBoef demonstrated the utility of the C2-selective oxidative cross-coupling of indole and benzene previously reported by his group in the expedient synthesis of a botulinum neurotoxin inhibitor (Scheme 10) [53]. The streamlined synthesis featured an oxidative cross-coupling of methyl-AT-SEM-indole-6-carboxylate with benzene, and after further elaboration, a direct arylation of a thiophene moiety that had been incorporated into the molecule. This formal synthesis highlights the efficiency of transition metal catalyzed reactions at C-H bonds in the planning of synthetic routes. 

Potavathri S, Kantak A, DeBoef B (2011) Increasing synthetic efficiency via direct C-H functionalization formal synthesis of an inhibitor of botulinum neurotoxin. Chem Commun. doi 10.1039/clccl0755k... 

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