Selectively Modified Cobyrinic Acid Derivatives

Abstract

A method for the synthesis of cobinamide derivatives by aminolysis of cobyrinate (CN)2Cby(III)(OMe)6(c-lactone) is described. Reactions catalyzed by a benzotriazole/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) system afford heptaamides in good yields. During aminolysis of heptamethyl cobyrinate hydroxylation occurred at the C8 position. DFT calculations indicate that the C-H bond at this position is the weakest and, as such, is the easiest to break. The use of (CN)2Cby(III)(OMe)6(c-lactone) circumvented the problem, as the hydroxy group is already present at the 8 position and can be easily removed by c-lactone reformation and subsequent reduction. Moreover, selective functionalization of heptaamides at either the c or meso position was also explored. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.