The New Synthesis Method Of Irbesartan As Antihypertensive Drug

Hypertension is a commonly and frequently encountered disease that severely endangered human health nowadays.There are about one billion people of the whole world suffering from this kind of disease and the number is increasing year by year. There are the most patients in our country.Hypertension is not only an independent disease,but also it can lead to the changes of structure and function in heart,brain, kidney,blood vessels,which could cause some related diseases.High rates of death and disability caused by complications of hypertension,which made patients and their families a heavy burden of spirit and financial.At present,the drug therapy is a primary means in the treatment of hypertension,which include six different kinds of drug categories.Because of its role in the exact step-down,minor adverse reactions, angiotensinâ…¡receptor antagonist have broad application prospects.Irbesartan is the one of angiotensinâ…¡receptor antagonist.It owns highest bioavailability,long plasma half-life,which can realize one time a day.There is no active metabolite and to be effective in preventing and reversal of hypertension-induced left ventricular hypertrophy,which has important practical significance.In the traditional method,it required the use of cyanide in the synthesis of Irbesartan.Cyanide is highly toxic,hazardous to the environment and not mass production.In the mean time,2-(n-Butyl) -1,3-diazaspiro[4,4]ono-1-ene-8-one would be produced,which is the isomer of 2-(n-Butyl) -1,3- diazaspiro[4,4]ono -1-ene-4-one.This by-product involved in the next step,which was difficult to be removed.This paper puts forward a new method of synthesis of irbesartan.The process includes two stages:first,glycine as the starting material,cycloleucine hydrochlorate was obtained by esterification,amidation,dehydration,a closed-loop and hydrolysis.And then,cycloleucine hydrochlorate as the starting material,the irbesartan was obtained by amidation,dehydration condensation,and coupled with the sodium azide.In this paper,the new synthesis method,it can not only avoid the use of cyanide,easy to get raw materials,high-yield of single-step reaction and easily purified,but also avoid the production of isomer,the mild rection conditions which can greatly shorten the time the cyclization reaction.In this paper,the total yield is 17.22%.The yield of first stage is 54.16%.If cycloleucine hydrochlorate could realize industrial production,the yield of Irbesartan will up to 31.81%.