NOUVEAUX PROCÉDÉS EFFICACES POUR LA SYNTHÈSE DE DÉRIVÉS DE TYPE TAXANE TELS QUE LE DOCÉTAXEL ET LEURS ANALOGUES STRUCTURAUX, ET PROCÉDÉ DE PRÉPARATION DE CES DERNIERS
SAFARI, Hatam,MOFAKHAM, Hamid,NAZARI, Saber,EISAPOUR, Elias,AZIMI, Hosein Ali,ROSTAMIAN, Ali Reza
申请号：
IBIB2015/059675
公开号：
WO2016/098015A1
申请日:
2015.12.16
申请国别(地区):
IB
年份:
2016
代理人:
摘要：
The present invention relates to a novel process for the preparation of taxanes such as Docetaxel, a very important anticancer drug. Docetaxel 1 is a clinically well-established anti -mitotic chemotherapy medication used mainly for the treatment of breast, ovarian and non-small cell lung cancer. In this work we introduce an efficient and simple process for producing Docetaxel 1 (vide infra), including the following steps: a) hydroxyl acylation reaction of 10-DAB-III with chloroacetic acid to obtaine compound 2； b) condensation reaction of compounds 2 and 3 to obtain compound 4； c) deprotection of protecting group paramethoxy phenyl (PMP) protecting group to obtain compound 5 d) deprotection of protecting group Rl of compound 5 to prepare Docetaxel 1； wherein, Rl is, among other acetylation reagents, chloroacetyl chloride, R2 is, among other ketones and aldehydes, paramethoxy phenyl (PMP), and R3 is, among other alkanes, tert-butyl e) subjecting the crude Docetaxel to fast filtration over a short silica gel filter to obtain anhydrous Docetaxel of >； 95% purity f) crystallizing the anhydrous Docetaxel of step e) to obtain pharmaceutical grade Docetaxel trihydrate. In the methods for preparation of the present invention, the protective groups used are easily removed, the purification of the intermediates is convenient, the cost of production is reduced, the steps of reaction are fewer, the yield and the purity are higher, and the processes can be scaled to commercial scale production. Another important aspect of the present invention is the preparation of pharmaceutical grade Docetaxel without resorting to chromatography.La présente invention concerne un nouveau procédé pour la préparation de taxanes tels que le Docétaxel, un médicament anticancéreux très important. Le Docétaxel 1 est un médicament chimiothérapeutique de type anti-mitotique bien établi cliniquement, utilisé principalement pour le traitement du cancer du sein, du cancer de l'ovaire et du cancer du pou
