Synthesis Of Antineoplastic Peptide Drug Buserelin

Prostate cancer is the second most frequently diagnosed cancer for male, especially inEuropean and American countries. In Asia, the morbidity is lower, but there is an increasedincidence trend. It was reported that about258000patients died from this disease annuallyin the worldwide. With the development of national economy and changing of lifestyles,the incidence of prostate cancer increased from1.71/100000in1993to10/100000in2010inChina. At the same time, breast cancer, endometriosis and uterine fibroids and othergynecological diseases are affecting the global women’s health. According to the WHOofficial website, there are about1.38million new cases and458000deaths from breastcancer each year in the worldwide. The incidence of breast cancer is about21.6/100000inour country, the endometriosis patients accounted for10~15%of women of childbearingage and there are20~30%of adult women suffering from varying degrees of uterinefibroids. These hormone-dependent diseases not only bring serious pain to the patient’sbody, but also greatly affect their life quality.The GnRH (gonadotropin-releasing hormone) analogues play an important role in thetreatment of hormone-dependent diseases. These analoguesare highly active at verylowdosage, their adverse reaction is small, and the curative effect from these drugs arestable. According to mechanism of action, GnRH analogues are divided into two categories:one is GnRH agonist, including Triptorelin, Buserelin, Goserelin and Leuprorelin, etc.; theGnRH antagonistinclude Cetrorelix, Ganirelix and Abarelix and so on. All these GnRHpeptide drugs demonstrated good curative effect; However, the high drug priceis a heavyeconomic burden for patients in developing countries. For this reason, the development ofgeneric peptide drugs with lower price is the aim of this research.Buserelin, launched in Germany firstly in1984, was developed and manufactured bySanofi-Aventis. It was sold mainly in Europe, Asia, parts of Latin America and Africa. InUSA, it is in clinical phase III. The patent protection is due in2015. This research is aimedto design and optimize a new segment condensation synthesis route to synthesize Buserelin.Combination of solid-liquid technology was applied. Our improved synthesis process is easy operating with high purity and yield, easy to scale up.