佛司可林分离纯化制备的研究

【作者】 刘庚贵；

【导师】 杜方麓；

【作者基本信息】 湖南中医药大学 ， 中药学， 2007， 硕士

【摘要】 毛喉靴蕊花(Coleus Forskohlii Willd.)被公认是唯一含有佛司可林的已知植物,佛司可林(forskolin,简写为FSK)为目前所知唯一从植物中得到的最强的腺苷酸环化酶激活剂。FSK通过直接激动腺苷酸环化酶(AC),提高多种组织细胞内的环腺苷酸(cAMP)浓度,从而参与多种细胞功能调节,在体内起着广泛的调节作用。临床上用于治疗充血性心力衰竭、肿瘤转移、青光眼、支气管哮喘、皮肤病等。本课题首先要解决的问题是制备佛司可林标准对照品。从产自印度的毛喉鞘蕊花提取物中分离出3个单体化合物,并对其结构和纯度加以鉴定。CompⅠ为佛司可林(FSK);CompⅡ为红色针晶,其溶液显光亮的金黄色,在实验中发现,该物质是一个影响毛喉鞘蕊花提取物及佛司可林色泽的化合物,经鉴定为:2,6,11,15-四甲基-2,4,6,8,10,12,14-七烯-1,16-二醛;CompⅢ为无色针晶,经TLC及HPLC鉴定,该物质是对佛司可林产生主要干扰的化合物,结构和性质与佛司可林相似,是制备高含量佛司可林过程中所存在的主要干扰杂质,经鉴定为:7β-乙酰氧基-6β,9β-二羟基-1,11,8,13-二环氧-labd-14-烯半日花烷。CompⅡ和CompⅢ为该属及该种植物中首次发现;从生物合成过程来说,CompⅡ与一般规律不同,即该二萜是由两个单萜尾尾相连而成,一般二萜是首尾相连而成,这在植物化学生物合成上是一个新例。利用自制的佛司可林单体化合物,进一步研究了制备佛司可林单体化合物的方法,即硅胶层析以及石油醚、乙酸乙酯重结晶;标准化毛喉鞘蕊花提取物的质量控制标准,建立并完善了HPLC法测定佛司可林含量的方法,为纯度判断和工艺研究奠定基础。在质量控制佛司可林含量的基础上,初步研究了工业生产中利用层析工艺和精制工艺制备高含量佛司可林的毛喉鞘蕊花提取物的方法:确定乙酸乙酯-石油醚为1:(8-10)之间,提取物-硅胶为1:(3-5)之间,可以直接生产出60%-80%的产品;再用石油醚与乙酸乙酯进行脱色及重结晶,可得到纯度高达90%的产品;同时探讨了Girard T试剂参与化学反应分离纯化含羰基化合物-佛司可林的可行性,证明此法不适用于分离纯化佛司可林,为进一步的工艺研究奠定基础。更多还原

【Abstract】 Coleus forskohlii Willd. is the only plants all known that contains forskolin. Forskolin (FSK)is the strongest activator of AC that extracted from botan.It can regulate many kinds of cyto-function in vio in the way of activating AC directly and raise cAMP of many histiocyte.The most important issue in this study was preparing the standard reference material.3 simple substance were isolated from Coleus forskohlii Willd. and were identified as following: Comp I was forskolin; Com II was 2,6,11,15-tetramethyl-2,4,6,8,10,12,14- seven alkene-1,16-di-aldehyde,a red needle crystal ,which can influence the colour of FSK; Com III was 7β-acetoxy -6β, 9β-dihydroxy-1,11,8,13-diepoxy 14-alkene -labd,a colorless needle crystal,which was the main impurity in the production of FSK.Comp II and CompIII were discovered in Coleus forskohlii Willd. and its family firstly. Based on the process of biosynthesis, its has another regularity, it is composed by two monoterpene with its end i.e, while other diterpenes is composed by head and end. It is a new sample in phytochemistry biosynthesis.A self-made monomer of FSK was applied to further the study on the production of FSKwith the methond of silica gel laminar analysis and the recrys of ligarine and acetic ether,to standardize the quality control of Coleus forskohlii Willd’s extractive,to improve the mensuration of FSK’s contents by HPLC and to settle foundation for the purity decision and technology research of FSK.Based on the quality control of FSK ,a method of preparing extractive of Coleus forskohlii Willd in industry ,rich in FSK,was studied initially.If acetic ether : ligarine were 1: 8-10,and extractive : gel silica were 1: (3-5), the purity of the products could be 60%-80% and that could be 90%.if use acetic ether and ligarine to decolor and recryst. Meanwhile, this study showed that Girard T was nonapplied to isolate and purify FSK,which settle the foundation to further the technology research.更多还原