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Synthesis of all the diastereomers of 2-amino-3-hydroxy-4,5- dimethylhexanoic acid

Abstract:

Herein, we describe an efficient stereoselective synthesis of all the diastereomers of 2-amino-3-hydroxy-4,5-dimethylhexanoic acid. The γ-branched carbon skeleton was set up by reaction of Garner's aldehyde with 2-lithio-3-methyl-2-butene. Hydrogenation (Pd/C catalyst) of the tetrasubstituted olefin proceeded smoothly with acceptable stereoselectivity, depending on the diastereomer hydrogenated. The final compounds were then obtained in 12-18 % overall yield through intramolecular cyclization, Jones oxidation, and hydrolysis in 5-7 steps from Garner's aldehyde. The three stereocenters of 2-amino-3-hydroxy-4,5-dimethylhexanoic acid can be set up at will in a stepwise manner starting from Garner's aldehyde without the need for any additional chiral reagent. The synthesis involves reaction with 2-lithio-3-methyl-2-butene, followed by hydrogenation, intramolecular cyclization, Jones oxidation, and hydrolysis. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.