Study On Synthesis Of Arylphosphonates And Phenol Substituted Aminobisphosphonates

Phosphonates is an important part of organophosphorus compounds. Aryl-and vinylphosphonic acid moieties are key functionalities in many biologically active compounds, flame retardants, or polymer additives. Dialkyl arylphosphonates are reported as important intermediates in the synthesis of pesticides, medicine and biologically active compounds.The latest research and development of arylphosphonates and phenol substituted aminobisphosphonates were reviewed in chapter one.The palladium catalyzed cross coupling aryl halide with diethyl phosphate using Dabco as ligand to synthesize arylphosphonate was investigated in chapter two. The arylphosphonate were obtained in moderate to good yields under the optimized reaction condition involving Pd(OAc)2 as a catalyst, Dabco as a ligand, acetone as a solvent, K2CO3 as a base at 110-115℃. It was noted that this protocol gave heteroaromatic phosphonates in good yields.Apomine, traisopropyl-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-ethyl-1,1-bisphosphonate, is a novel antineoplastic agent. Apomine inhibits the growth of cancer cells from a number of cancer types, including lung colon, breast and skin. Additionally, it induces apoptosis in tumor cell lines derived from leukemia, colon, liver, ovary and breast cancers. It also has positive results for the treatment of melanoma. Based on the rationale of lead compound optimization that take advantage of bioisosterism, we anticipate to get an kind of phenol substituted aminobisphosphonates with higher biological activity and lower toxicity that derived from the structure modification on apomine through Me-too approach in chapter three. The three novel compounds were synthesized using diethyl phosphonate as starting material by 13 steps via three different synthesis route. Further research work on antitumor activity in vitro is in progress.