An efficient large-scale synthesis of gemcitabine employing a crystalline 2,2-difluoro-alpha-ribofuranosyl bromide

作者：Chang Young Kil; Lee Jaeheon; Park Gha Seung; Lee Moonsub; Park Chul Hyun; Kim Han Kyong; Lee Gwansun; Lee Bo Young; Baek Ju Yuel; Kim Kwan Soo^*

来源：Tetrahedron, 2010, 66(30): 5687-5691.

DOI：10.1016/j.tet.2010.05.039

• Gemcitabine
• Nucleoside
• Ribofuranosyl bromide
• Ribofuranosyl phosphate

An efficient large-scale synthesis of gemcitabine was achieved without chromatography or fractional crystallization. The key steps include stereospecific conversion of a novel beta-ribofuranosyl phosphate into a highly crystalline alpha-ribofuranosyl bromide and coupling of the alpha-ribofuranosyl bromide and trimethylsilyl cytosine to produce a beta-nucleoside. p-Phenylbenzoyl group was introduced for the protection of one of hydroxy groups in order to enhance the crystallinity of intermediates. Continuous removal of trimethylsilyl bromide, generated during the coupling reaction, by distillation from the reaction medium substantially enhanced the beta-selectivity of the crucial coupling reaction.

• 出版日期2010-7-24