高三尖杉酯碱的合成及其差向异构体的分离鉴定  

SYNTHESIS OF HOMOHARRINGTONINE AND SEPARATION OF ITS STEREOMERS

作　　者：王永铿 李裕林[1] 潘鑫复[1] 李绍白[1] 黄文魁 

机构地区：[1]兰州大学有机化学研究所 [2]福建中医研究所

出　　处：《化学学报》1985年第2期161-167,共7页Acta Chimica Sinica

基　　金：中国科学院科学基金

摘　　要：1-溴-4-氧戊烷的乙二醇缩酮(1)的格氏试剂,与草酸二乙酯反应,得2,6-二氧-6-乙二醇缩酮庚酸乙酯(2).2经相应的钠盐3、酰氯4再转化成α-酮酰基三尖杉碱(5).5经Reformatsky反应,酸性水解后与碘甲烷的格氏试剂反应.所得产品经pH梯度萃取并结合氧化铝干柱层析纯化,得到高三尖杉酯碱及其差向异构体的混合物8.然后制成苦味酸盐,经分级结晶,再分别转化成游离碱8a及8b.8a的HNMR,MS,IR(film).和TLC与天然高三尖杉酯碱完全一致.8b的MS和IR与8a极为相似,但它们的HNMR却有明显差异,因此可以确定它们互为差向异构体.Ethyl 2-oxo-6-ethylene dioxy-heptanoate(2),an important intermediate in the preparation of homoharringtonine(8a),was prepared by the reaction of Grignard reagent made from 1-bromo-4-ethylene dioxy pentane with ethyl oxalate in THF.Compound 2 was converted intoα-keto-acyl-cephalotaxine(5)via sodium carboxylate 3 and acyl chloride 4.Reformatsky reaction of 5 with methyl bromoacetate in the presence of freshly prepared active zinc affords 6.Acid treatment of 6 gave 7.Reaction of 7 with methyl magnesium iodide provided a mixture of homoharringtonine(8a)and its epimer 8b.Their separation is effected by fractional crystallization of their picrates and subsequent recovery of the free alkaloids 8a and 8b.The TLC,IR,~1H NMR and MS data of 8a are identical with those of natural homoharringtonine.The IR and MS of 8a and 8b are quite similar,but their~1H NMR are markedly different.

关 键 词：差向异构体 缩酮 庚酸 反应 三尖杉碱 植物抗癌药 苦味酸盐 

分 类 号：O62[理学—有机化学]