神经肌肉阻滞剂罗库溴铵有关物质D的制备

目的合成1-3α-乙酰氧基-17β-羟基-2β-(吗啡啉-4-基)-5α-雄甾烷-16β-基]-1-(丙烯-2-基)四氢吡咯鎓溴化物(有关物质D)。方法以2α,3α,16α,17α-二环氧-17-乙酰氧基-5-雄甾烷为起始原料,经吡咯烷开环、硼氢化钠还原、开环反应、酰化反应等反应,经柱层析分离纯化拆分了三种光学异构体,合成(2β,3α,5α,16α,17β)-2-(4-吗啉)-16-(1-吡咯基)-雄甾-3,17-二醇3-乙酸酯,然后经催化和烯丙基溴反应合成了有关物质1-3α-乙酰氧基-17β-羟基-2β-(吗啡啉-4-基)-5α-雄甾烷-16β-基]-1-(丙烯-2-基)四氢吡咯鎓溴化物(有关物质D)。结果其结构经1H-NMR和LC-MS证实。结论该合成方法能够合成罗库溴铵有关物质D,为控制产品质量提供有关物质对照品。

Synthesis of related substance D of neuromuscular blocking agents rocuronium bromide

OBJECTIVE To study the synthesis of the compound 1-3α-（acetoxy）-17β-hydroxy-2β-（morpholin-4-yl）-5α-androstan-16β-yl]-1-（prop-2-enyl）pyrrolidinium bromide（related substance D）.METHODS The compound（2β,3α,5α,16α,17β）-2-（4-morpholinyl）-16-（1-pyrrolidinyl）-5α-androstan-3α,17-diol-3-actes was synthesized by using 2α,3α,16α,17α-diepoxy-17b-acetoxy-5a-androstane as the starting material via the ring-opening,reduction,ring-opening,acylation reactions,and then separated and purification resolution 3 type optical isomer by column chromatograph.The compound 1-3α-（acetoxy）-17β-hydroxy-2β-（morpholin-4-yl）-5α-androstan-16β-yl]-1-（prop-2-enyl） pyrrolidinium bromide（related substance D） was synthesized with via catalytic reaction and allyl group brom reaction.RESULTS The structure was identified by 1H-NMR and LC-MS.CONCLUSION The related substance D of Rocuronium Bromide can be synthesized by this method,and provide related substances reference standards for controlling the product quality.