Starting from natural molecules, for example l-menthol and amino acids, a series of 2(5H)-furanone liquid-crystal compounds were designed, and synthesized by esterification of N-[5-menthoxy-2(5H)-furanonyl] amino acids with biphenyl-4-ol or biphenyl-4,4′-diol in the presence of dehydrating agents. The structures of all the novel compounds were confirmed by FTIR, 1H NMR, and mass spectroscopy, and by elemental analysis. The liquid-crystal properties of the target compounds were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and polarization optical microscopy (POM). The DSC and XRD results showed that some compounds containing short alkyl chains or with the phenyl far from the amino in the amino acid unit formed a mesomorphic phase. Products obtained from biphenyl-4,4′-diol were more likely to form a mesomorphic phase. However, POM revealed no optical texture. These investigations provide, for the first time, a basis for application of 2(5H)-furanones in liquid crystals by combination of different functional units, including biphenyl, l-menthol, and amino acids.