Study Of Minodronic Acid Syntheis Process

Osteoporosis, a kind of bone metabolism abnormal caused by many reasons. The disease's characterized is bone tissue degradation and low bone mineral density, It is a chronic disease. Before fracture, generally do not have any special situation.The proportion of women is high, the disease is common in postmenopausal women and the elderly.Along with the increase in China's aging population, incidence of a disease in a rising trend.Minodronic acid, which brand name is Bonoteo (?), is the third new heterocycle diphosphonate compound, developed by Astellas and ??company. It was approved for treating osteoporosis by lowering the bone reabsorption and affecting the spongy bone transfer to cortical bone and bone quality in Japan 2009. This compound can effectively inhibit the absorption of osteoclast, reducing bone metabolism cycle, and then play an important role in the treatment of osteoporosis. Compare to other diphophonate compounds, minodronic acid could significantly improve the accelerating bone mass loss of the postmenopausal women and the elderly osteoporosis. Besides, the dose of this drug is clearly lowed,which promote the compliance of patients, as well as reduce the normal adverse of diphosphonate compound.Here, we design and optimize the synthetic routes of minodronic acid referring to hundreds of articles: 2,2-Dimethoxyacetaldehyde and Triethyl phosphonoacetate are synthesis to 4, 4 - dimethoxy - 2 -crotonic acid ethyl ester, then through cyclization, hydrolysis, phosphorus tribromide and hydrolysis reaction to get Minodronic acid.We used several analytic methods, infrared spectrum and nuclear magnetism spectrum, to confirm its structure in every synthetic route.After optimization, the whole processes become easily operation, low cost and equipment-needed, little pollution. Moreover, it seems like we have more easier getting and cheaper materials to realize its commercial process.