A focus on the asymmetric synthesis of a novel threo-β-benzyl-β-hydroxy aspartate analogue

Considering the biological activity of β-alkyl-β-hydroxyaspartate derivatives as potent blockers of glutamate transporters (EAATs) impacting on glutamatergic synapses activity, we have developed a concise, asymmetric synthesis of enantiomerically pure threo-β-benzyl-β-hydroxyaspartates. The key step is a regiospecific and stereoselective Sharpless asymmetric aminohydroxylation (SAA) on previously synthesized benzyl fumarate.

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(2S,3S)-3-Amino-2-benzyl-2-hydroxysuccinic acidC11H13NO5ee >99%[α]D20=+20.0 (c 0.3, DMSO)Absolute configuration: (2S,3S)

(2S,3S)-Dibenzyl 2-benzyl-2-hydroxy-3-(4-methylphenylsulfonamido)succinateC32H31NO7See >99%[α]D20=-102.0 (c 0.5, DCM)Absolute configuration: (2S,3S)