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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.

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

Lipophilic, steric, electronic, and enzyme resistance characteristics of carboranylalanine, adamantylalanine, neopentylglycine and tert-butylglycine are described. The first 2 amino-acids display lipophilicities 2 orders of magnitude higher than tryptophan.