A novel norstatine derivative, phenylthionorstatine [(2R, 3R)-3-amino-2-hydroxy-4- (phenylthio) butyric acid; Ptns], containing a hydroxymethylcarbonyl (HMC) isostere was designed, synthesized, and stereochemically determined. Then, Ptns was introduced into the structure of BACE1 inhibitors at the P1 position. Finally, Ptns was found as a suitable P1 moiety for potent BACE1 inhibitor design.