Enantiopure β3-neopentylglycine: synthesis and resolution

A procedure has been developed for the large scale synthesis of enantiopure β3-neopentylglycine and its Cbz-protected derivative. The synthetic route developed in our laboratory features Cbz-protection of the racemic β-amino acid followed by resolution with l-norephedrine and provides the enantiomerically pure Cbz-β-neopentylglycine in good yield and excellent enantiopurity. No toxic or dangerous chemicals are used, allowing the scale-up of this procedure without major safety concerns.

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(S)-3-Benzyloxycarbonylamino-4,4-dimethylpentanoic acid, l-(−)-Norephedrine saltC24H34N2O5[α]D20=-6.4 (c 1, EtOH)Source of chirality: resolutionAbsolute configuration: (S)

(S)-3-Benzyloxycarbonylamino-4,4-dimethylpentanoic acid; (S)-Cbz-β-neo-pentylglycineC15H21NO4[α]D20=+13.4 (c 1.4, CHCl3)Source of chirality: resolutionAbsolute configuration: (S)

(S)-3-Amino-4,4-dimethylpentanoic acid; (S)-β-neopentylglycineC7H15NO2[α]D20=-67.7 (c 1, H2O)Source of chirality: resolutionAbsolute configuration: (S)