Synthesis and physicochemical property of the hydrophobic bisphosphate amidated derivatives

Hydrophobic bisphosphate amidated derivatives (1a-1d) anchored long alkyl chains were designed and obtained through the reaction of -NH₂ in BPs and -COOH in fat acid under anhydrous condition. The structure of derivatives were investigated by fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and mass spectrometer (MS) and the results showed that the final products were amidated compounds with the long alkyl anchored in alendroante´s lateral chain R₂. The physicochemical parameters, such as the solubility and partition coefficient in n-octanol/water, were also determined through calculated by performing reversed phase high performance liquid chromatography (RP-HPLC). Compared with alendronate, the derivatives had a very low aqueous solubility and had little or even no measurable solubility values in PBS. While it had different solubility in organic solvents with different polarities. The partition coefficient P_o/w of derivatives in n-octacol/water mixture was calculated and the results showed that the derivatives had the high P_o/w data than that of alendronate and the longer the alkyl chain was introduced, the higher the partition coefficient was. All of the above results showed the improved lipophilicity of the derivatives through long alkyl chain introduced into its R₂ chain.