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目的研究SGLT2抑制剂LX4211的合成方法。方法以L-(-)-木糖为起始原料,经羟基保护、氧化、酰胺化得到中间体(5S)-1-C-4-吗啉基-4,5-O-异亚丙基-D-2,5-呋喃木糖二醛,该中间体与5-溴-2-氯-4’-甲氧基二苯甲烷缩合,再经还原、脱保护、开环扩环、酯化、溴代、硫醚化、醇解得到目标化合物LX4211。结果与结论优化并确定了LX4211的合成路线,总收率由18.1%提高至23.2%(以L-(-)-木糖计),其结构经1H-NMR和MS确证。该路线成本较低、操作简便、条件温和、收率高,具有工业化生产的潜力。
Objective To study the synthesis of SGLT2 inhibitor LX4211. Methods L - (-) - xylose was used as starting material to afford (5S) -1-C-4-morpholinyl-4,5-O-isopropylidene -D-2,5-furanyl xanthic aldehyde which is condensed with 5-bromo-2-chloro-4’-methoxydiphenylmethane and then reduced, deprotected, ring opened and ring extended, esterified , Bromination, thioetheration and alcoholysis gave the target compound LX4211. RESULTS AND CONCLUSIONS The synthetic route of LX4211 was optimized and confirmed. The overall yield of LX4211 was increased from 18.1% to 23.2% (calculated as L - (-) - xylose). The structure was confirmed by 1H-NMR and MS. The route is low cost, easy to operate, mild conditions, high yield, with the potential of industrial production.