Firstly, (S)-2-[(benzyloxycarbonyl)amino]-3-(benzyloxy)propyl phosphonate (Ⅱ) was synthesized after diphenyl phosphite treatment of easily prepared (S)-benzyloxy-2-((benzyloxycarbonyl)amino)-3-hydroxypropanoate (Ⅰ). Secondly, a new compound (R)-2,3-isopropylidene-sn-glyceryl{(S)-2-[(benzyloxycarbonyl)amino]-3-(benzyloxy)-1-oxopropyl}phosph-onate (Ⅳ) was prepared by a one-pot condensation-oxidation procedure. After the pivaloyl chloride mediated activation of compound Ⅱ, condensation with (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol (Ⅲ), and obtained by iodine mediated oxidation. Then, the protective group of isopropylidene was removed by trifluoroacetic acid (TFA) to obtain the key intermediate, (R)-2,3-dihydroxypropoxy-sn-glyceryl{(S)-2-[(benzyloxycarbonyl)amino]-3-(benzyloxy)-1-oxopropyl}pho-sphonate (Ⅴ). Next, the compound Ⅴ was acetylated further with stearic acid at the function in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) to give (R)-2,3-bis(Stearoyloxy)popyl{(S)-2-[(benzyloxycarbonyl)amino]-3-(benzyloxy)-1-oxopropyl}phosphonate (Ⅵ) with a great yield. Finally, 1,2-distearoyl-sn-glycero-3-phosphatidylserine (Ⅶ) was synthesized by hydrogenolysis of benzyloxycarbonyl (-Cbz) and benzyloxy (-Bn) protective groups. Finally, the main steps were optimized for reaction conditions, and it was verified and amplified. The synthesis of compound Ⅶ was only 5 steps with a total yield of 57.0%. The structure of final compound Ⅶ was confirmed by FTIR, HRMS and NMR