Microbial oxidation of aromatics in enantiocontrolled synthesis. 2. Rational design of aza sugars (endo-nitrogenous). Total synthesis of +-kifunensine, mannojirimycin, and other glycosidase inhibitors.

A general method of synthesis for lactones and lactams related to carbohydrates has been developed that relies on the biocatalyticgeneration of 1-chloro-2,3-dihydroxycyclohexa-4,6-diene (l), obtained in excellent yield by fermentation of chlorobenzene with Pseudomonasputida 39D, followed by further functionalization to nitrogen-substituted cyclitols. These amino or azido cyclitols of type 15 are then subjected to controlled ozonolysis, which yields either lactones such as 27 or lactams containing five-membered (28) or six-membered (20 and 23) rings. Such compounds are useful intermediates for the preparation of aza sugars. Mannojirimycin (84 has been synthesized in seven steps from chlorobenzene. Kifunensine (7) has been prepared in 11 steps from chlorobenzene following an intersection with Hashimoto's procedure. Full experimental and spectral details are provided for all compounds. The potential of this general method and implications of the disclosed design features in the field of amino sugar and aza sugar synthesis are indicated.