Stereoselective synthesis of spiro[5.5]undecane derivatives via biocatalytic [5+1] double Michael additions

A novel enzymatic, promiscuous protocol of D-aminoacylase (DA)-catalyzed [5+1] double Michael addition was developed herein, for the synthesis of (hetero)spiro[5.5]undecane derivatives in moderate yields. It is notable that almost only the cis isomers were obtained through this biocatalytic methodology in all the cases according to their H-1 and C-13 NMR spectra. It is the first report on hydrolase-catalyzed double Michael addition in organic solvent. (C) 2013 Elsevier B.V. All rights reserved.