正交设计优化地塞米松琥珀酸单酯合成工艺

目的 探讨以正交实验优化地塞米松琥珀酸单酯（DSH）的合成工艺。方法 以4 二甲氨基吡啶（4-DMAP）为催化剂，将地塞米松（DEX）与琥珀酸酐反应制备DSH。以琥珀酸酐与DEX及催化剂4-DMAP与DEX的摩尔比为影响因素，设计两因素三水平的正交实验，以目标产品DSH的收率作为判断指标，优化DSH的合成工艺。结果 4-DMAP与DEX的摩尔比为影响DSH收率的主要因素，琥珀酸酐与DEX的摩尔比为次要因素；优化的合成条件为：DEX：琥珀酸酐：4-DMAP的摩尔比为1.0：2.0：0.5。优化工艺后DSH收率为97.72%，合成的产物经磁共振鉴定为目标合成物，纯度大于99.0%。结论 优化的合成工艺大大提高了产品收率，工艺稳定且易于控制。

Optimum Technology for Synthesizing Dexamethasone Hemisuccinate by Orthogonal Test

Objective To explore the synthetic technology of dexamethasone hemisuccinate(DSH) by orthogonal test. Methods DSH was synthesized with dexamethasone and succinic anhydride,using 4-Dimethylaminopyridine(4-DMAP) as catalyst.The synthetic technology was optimized by orthogonal test with two factors and three levels,with the yield of DSH being the criteria.The factors were the molar ratio between succinic anhydride and dexamethasone and the molar ratio between 4-DMAP and dexamethasone. Results The molar ratio between 4-DMAP and dexamethasone was the main factor affecting the yield of DSH and the molar ratio between succinic anhydride and DSH was the minor one.The optimum molar ratio among dexamethasone,succinic anhydrate and 4-DMAP was 1.0:2.0:0.5.The yield of DSH from optimum technology was 97.72%.HNMR and IR results showed that the obtained product was what we wanted and its purity was above 99.0%. Conclusion The optimum technology for synthesizing DSH raised the yield of DSH in large scale and the technology was stable and easy to control.