Synthesis of some trifluoromethylated cyclodextrin derivatives and analysis of their properties as artificial glycosidases and oxidases

Cyclodextrin derivatives containing trifluoromethyl groups at C6 of the A and D rings were synthesized for the purpose of creating artificial enzymes. The compounds were synthesized by perbenzylation of beta-cyclodextrin followed by selective A,D-debenzylation according to Sina. Subsequent oxidation to dialdehyde with Dess-Martin periodinane followed by addition of CF3 by using Arduengo carbene and TMSCF3 led to the C-6-bistrifluoromethylated alcohols. These were either deprotected by hydrogenolysis or subjected to another round of oxidation to provide the corresponding ketones that were deprotected. The trifluoromethylated alcohols were found to be weak artificial enzymes catalysing hydrolysis of nitrophenyl glycosides at neutral pH with a k(cat)/k(uncat) of up to 56. It is proposed that this catalysis is analogues to the catalysis performed by related cyanohydrins. The trifluoro ketones were likewise weak articial enzymes catalysing oxidation of amines to nitro derivatives or alcohols to ketones with a k(cat)/k(uncat) of up to 133. (C) Wiley-VCH Verlag GmbH & Co.