1173824-58-2Relevant articles and documents
Thiophene-expanded guanosine analogues of Gemcitabine
Chen, Zhe,Ku, Therese C.,Seley-Radtke, Katherine L.
, p. 4274 - 4276 (2015)
The chemotherapeutic drug Gemcitabine, 2′,2′-difluoro-2′-deoxycytidine, has long been the standard of care for a number of cancers. Gemcitabine's chemotherapeutic properties stem from its 2′,2′-difluoro-2′-deoxyribose sugar, which mimics the natural nucleoside, but also disrupts nucleic acid synthesis, leading to cell death. As a result, numerous analogues have been prepared to further explore the biological implications for this structural modification. In that regard, a thieno-expanded guanosine analogue was of interest due to biological activity previously observed for the tricyclic heterobase scaffold. Several analogues were prepared, including the McGuigan ProTide, however the parent nucleoside exhibited the best chemotherapeutic activity, specifically against breast cancer cell lines (89.53% growth inhibition).
Purification method of gemcitabine intermediate
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Paragraph 0079-0080, (2021/06/22)
The invention provides a purification method of a gemcitabine intermediate, and belongs to the technical field of drug intermediate synthesis. According to the invention, a compound 2 in an existing method (shown in a formula 1 and a formula 2 in a background art) is reduced to obtain a mixture containing a compound 3 and a byproduct compound 9; the mixture reacts with aniline; dehydration condensation reaction of the compound 3 and aniline is achieved; Schiff base is generated; the Schiff base and the byproduct compound 9 are easy to separate; a high-purity compound 3 can be obtained by performing simple acidic hydrolysis and separation on the separated Schiff base; the high-purity compound 3 is subjected to sulfonylation reaction to synthesize a gemcitabine hydrochloride key intermediate compound 5, so that the yield and the purity of the compound 5 can be improved, and the preparation yield and the product quality of the raw material medicine gemcitabine hydrochloride are ensured.
Stereoselective N-glycosylation with N4-acyl cytosines and efficient synthesis of gemcitabine
Liu, Tongchao,Tang, Jiadeng,Liang, Jianpeng,Chen, Yabin,Wang, Xiaowen,Shen, Jingkang,Zhao, Dongmei,Xiong, Bing,Cen, Jun-Da,Chen, Yue-Lei
, p. 1203 - 1213 (2019/01/29)
Through systematical comparison of various N4-protected cytosine derivatives in the glycosylation step of gemcitabine synthesis, highly beta-stereoselective and high yielding TBAI catalyzed N-glycosylation was achieved with N4-Bz cytosine and anomeric mixture of 2,2‘-difluororibose mesylate donor. The subsequent global deprotection gave gemcitabine efficiently. Meanwhile, the anomeric chloride intermediate and fluoride-displaced side products of this N-glycosylation were identified, too. This new glycosylation method reveals the importance of N4-protection in the stereoselective preparation of pyrimidine nucleoside, also provides a potential alternative to current industrial process to gemcitabine.
