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Recent Research

Dynamic Kinetic Resolutions of Alpha-Keto Esters and their Derivatives

 

 

A method for the asymmetric synthesis of enantioenriched anti-α-hydroxy-β-amino acid derivatives by enantioconvergent reduction of the corresponding racemic α-keto esters is presented. The requisite α-keto esters are prepared via Mannich addition of ethyl diazoacetate to imines followed by oxidation of the diazo group with Oxone. Implementation of a recently developed dynamic kinetic resolution of β-substituted-α-keto esters via Ru(II)-catalyzed asymmetric transfer hydrogenation provides the title motif in routinely high diastereo- and enantioselectivity.

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Enantioselective Synthesis of the Complex Aminocylitol Pactamycin

 

For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Here, a short asymmetric total synthesis of pactamycin is presented. An enantioselective Mannich reaction and symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical stereochemical functional group relationships. This modular route totals 15 steps and is immediately amenable for structural analog synthesis.