公开(公告)号：EP3686208A1

公开(公告)日：2020-07-29

申请号：EP19861292.1

申请日：2019-11-07

申请人： Beijing Tienyi Lufu Pharmatech Co. Ltd.

发明人： XU, Weiping

IPC分类号： C07F7/18

摘要： The invention relates to intermediates useful in the preparation of halichondrin compounds, methods for preparing the same and use thereof, such as halichondrins, eribulin, or their analogs. The intermediates, the methods and use thereof are used for the synthensis of the C20-C26 fragment of halichondrin compounds. The raw materials in the synthetic route of the invention are cheap and easily obtained, the sources and the qualities of the raw materials are reliable. The choice of the methods useful in the synthesis of chiral central structures are based on the structural characteristics of the reactants, thus effectively improving the synthesis efficiency, reducing the difficulties and risks of product quality control, and avoiding the use of highly toxic and expensive organotin catalysts to significantly decrease costs and improve environmental friendliness.

公开(公告)号：EP3925948A1

公开(公告)日：2021-12-22

申请号：EP20796052.7

申请日：2020-04-02

申请人： Beijing Tienyi Lufu Pharmatech Co. Ltd.

发明人： XU, Weiping

IPC分类号： C07C43/23 ,  C07C41/26 ,  C07D303/04 ,  C07D301/24 ,  C07D317/22 ,  C07D407/06 ,  C07F7/08 ,  C07F7/18

摘要： The present invention relates to the field of drug synthesis, and particularly relates to an intermediate of eribulin and a synthesis method and use thereof. The present invention provides an intermediate useful for the synthesis of halichondrin B, eribulin or an analog thereof, particularly a structural fragment C27-C35 thereof, and a preparation method and use thereof. The starting materials of the synthetic route disclosed herein are cheap and easy to obtain, and the optical purity of the starting materials can be ensured, so that the optical purity of the structural fragment C27-C35 in halichondrin B, eribulin or the analog thereof is ensured; steps for constructing a chiral center of the structural fragment C27-C35 feature higher diastereoselectivity and yield, in particular preparation methods of compounds of formulae (X), (XI), (XVI) and (XV); by-products of partial reactions can be removed only by recrystallization, which results in easy purification and significant reduce in cost.

公开(公告)号：EP3608323A1

公开(公告)日：2020-02-12

申请号：EP19761378.9

申请日：2019-03-01

申请人： Beijing Tienyi Lufu Pharmatech Co. Ltd.

发明人： XU, Weiping

IPC分类号： C07D493/04 ,  C07D309/10 ,  A61K31/335 ,  A61P35/00

摘要： The present invention relates to pyran-fused ring compounds, preparation methods thereof and use thereof, especially to pyran-fused ring compounds usable for preparing Halichondrin, Eribulin, or analogues thereof, preparation methods thereof and use thereof. Use of any of the compounds of formula (I) to (XIII) of the present invention in preparation of Halichondrin B, Eribulin, analogues thereof or C1-C13 moieties thereof. Provided in the present invention are intermediates usable for preparing Halichondrin B, Eribulin, or analogues thereof, especially the key product of C1-C13 moieties, preparation methods thereof and use thereof. The starting material for the synthesis pathway of the present invention is inexpensive and readily available with sustainable source and reliable quality. Since the structural characteristics of the reactants of theirself are made full use in choosing the method of constructing the chiral centers, the efficiency in the synthesis is considerably increased, the difficulty in and the risk on quality control of the product are reduced; and using a highly toxic and expensive high-valent osmium catalyst is avoided, which have the cost and environmental friendliness significantly improved.