New aminocyclitols with quaternary stereocentres via acylnitroso cycloaddition with an ipso,ortho arene dihydrodiol

Microbial ipso,ortho-dihydroxylation of benzoic acid by the B9 mutant strain of Ralstonia eutropha permits rapid construction of aminocyclitols containing a quaternary stereocentre. Installation of the amine functionality is achieved by use of an acylnitroso dienophile for a hetero-Diels-Alder reaction. Both aminotetrols and aminohexols are accessible as single enantiomers by this route. Both NOESY spectroscopic and X-ray crystallographic analyses were required to distinguish cycloadduct isomers. Notably, subsequent to the biooxidation step, all new stereocentres are installed under substrate control. Thus, all stereochemical information is ultimately of enzymatic origin. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.