Synthetic routes following a sequential MacMillan organocatalytic asymmetric α-fluorination protocol for aldehydes and then reductive amination, have allowed ready access to bioactive β-fluoroamines. The approach is demonstrated with a short synthesis of (S)-3-fluoro-γ-aminobutyric acid (3F-GABA) and was extended to β-fluoroamine stereoisomers of cinacalcet, tecalcet, fendiline and NPS R-467, all allosteric modulators of the calcium receptor (CaR). Stereoisomers of the fluorinated calcimimetic analogues were then assayed in a CaR receptor assay and a comparison of β-fluoroamine matched pair stereoisomers revealed a binding mode preference to the receptor as deduced from conformations which will be favoured as a consequence of the electrostatic gauche effect.

按照连续的麦克米伦有机催化不对称α-醛化方案然后还原胺化的合成路线，可以随时获得具有生物活性的β-氟胺。该方法通过 ( S )-3-氟-γ-氨基丁酸 (3F-GABA) 的简短合成得到证明，并扩展到西那卡塞、替卡塞、芬地林和 NPS R-467 的 β-氟胺立体异构体，这些药物的所有变构调节剂钙受体（CaR）。然后在 CaR 受体测定中对氟化拟钙剂类似物的立体异构体进行测定，并且对 β-氟胺匹配对立体异构体的比较揭示了对受体的结合模式偏好，如从构象推断出的，这将由于静电疏忽效应而受到青睐。