齊魯藥事●Qilu Pharmaceutial Affairs 2007 VoL 26 .No.9●557●Candidate Journal of Medicinal Chemistry,1992 ,35(6) :1049.toprazole and intrmediates therefore. W002/28852 Al, 2001 -[2]Sannders, D, Lawrise K. w. M The syathesis of pantoprazole-10-01. .An H+/ K+ ATP inhibitor. J Label Compd Radiopharm 1992,[5] Alberto Palomo Coll, Deborah Palomo, et al. Proces for the31 ,5,409.preparation ol pantopratole and intermediaterthere-[3]BEKHAZI, Michel et al Synthesis of Omeprarole- type pyridinefore. U5200/0049044 A1.2004-03-11.derivatives and Intermediates thereol. W097/29103. 1997- 02 -[6]Brennen J P, Turoer A. I. Chemical process for cthe production05.of sulphinyl derivtives by oxidation of the correspondiny co-de-[4]Palomo Coll, Alberto et al. A process for the preparation of pan-rivatives with perborates. W09947514.氟比洛芬酯的合成，國大亮,孫晉瑞' ,朱曉薇(天津中醫(yī)藥大學,天津300193;1. 山東省醫(yī)藥工業(yè)研究所,山東濟南250100)摘要:目的考察氟比洛芬酯的合成工藝。 方法將四氫荼與液追反應，生成的澳化氫氣體溶于無水乙酸,將此溶液與 .醋酸乙烯酯反應。生咸乙酸- -1- 渙乙酯，氟比洛芬與乙酸-1-渙乙酯縮合,生成氟比洛芬酯。結果及結論此合成工藝原料易得、操作簡便,適于氟比洛芬酯的開發(fā)與生產(chǎn)。關鍵詞:氟比洛芬酯鎮(zhèn)痛合成中團分類號:T0460.31文獻標識碼:A 文章編號 :1672 - 7738{2007)09- 0557 -02Syntbesis of Flurbiprofen AxetilGUO Da-liang,SUN Jin-rui' ,ZHU Xiao wei(Tianjin University of Traditional Chinese Medicine, Tianjin.300193; 1. ShandongInstitute of Pharmaceutical Industry, Ji' nan,250100)ABSTRACT :OBJECTIVE To synthesice Flurbiprofen Axetil. METHODS Tetrahydronaphthalene was treated with bro-mine to produce hydrogen bromide. The hydrogen bromide was dissolved in anhydrous acetie acid, and this solution was reactedwith vinyl acetate to prepare 1- (acetoxy) ethyl bromide. Flurbiprofen Axetil was synthesized by esterfication of Flurbiprofenwith 1- (acetoxy) ethyI bromide. RESULIS and CONCLUSION Raw materiels are casily obtained. Synthesis route is simpleand suitable for development and manufacture.KEY WORDS:Flurbiprofen Axetil, analgesicsisynthesis氟比洛芬酯是非甾體抗炎藥氟比洛芬的酯類前體藥物,2實驗部分采用靜脈乳劑劑型,以卵磷酯包封成脂微球.鎮(zhèn)痛效果迅速、2.1 無水乙酸的制備叨取冰醋酸 120mL,倒人干燥撓杯持久,對癌癥性疼痛和術后疼痛臨床療效明顯“1。本品由日中,冰水浴冷卻,使冰醋酸凍結.傾倒到布氏濾斗中,抽濾掉本科研制藥株式會社和綠十字制藥株式會社聯(lián)合開發(fā),國內未凍結的液體,將剩余的固體轉入250mL帶有氯化鈣干燥目前尚無氟比洛芬酯合成工藝的報道,我們查閱了有關文器的四頸瓶中,加入1. 5g五氧化二磷回流2b,常壓蒸餾,收獻,總結并設計了氟比袼芬酯的制備工藝路線。集117~118C的餾分,制得無水乙酸103mL。1合成路線2.2澳化氫-無水乙酸(3)的制備的 向帶 有氯化鈣干燥器的四頸瓶中加入四氫素(2) 40 g.鐵粉a. 5g,冷水浴冷卻.保持內溫0~5C .攪拌下滴加液溴(104g) ,控制滴速,生成的氣體經(jīng)濃藐酸干燥后導人到96mL無水乙酸中,未吸收的尾氣用濃氫氧化鉀溶液中國煤化工達到145g為止(氫溴酸的濃鞍(3)。2.3乙YH. CNMHG上達漠化年一無水乙酸(3)溶液冷卻,保持內溫0~5C,在攪拌下慢慢加入醋酸乙烯酯(4>)43g(0.5mol) ,加完后繼續(xù)攪拌1b,加入200mL●558●齊春藥事Qiu Phamacuia Affairs 2007 Vol. 26.Na.9二氯甲烷稀釋,將反應液倒入到300mL冰水混合物中,分出重要。乙酸-1-溴丙酯.乙酸-1-氯乙酯和亞乙基二乙酸有機層,蒸餾水洗滌(2X 200mL),分取二氯甲烷層,無水硫酯中的離去基團分別為Br.Cl和0C0CH,這三個基團的堿酸鈉干燥,減壓濃縮除去溶劑,將剩余物臧壓蒸餾,收集122性順序為Br>CI>0C0CH ,Br原子最易離去,所以乙酸一~125C/738mmHg餾分,得乙酸一1- 溴乙酯(5)無色液體1-溴丙酯的反應活性最佳。5lg,收率61%。4結論2. 4氟比洛芬酯(1)的合成的向 250mL四頸瓶加入氟比洛本文將四氫荼與液溴反應,生成的溴化氫氣體溶于無水芬12. 2g(0.05mol) ,碳酸氫鉚8g,攪拌下加人丙酮110mL,乙酸,將此榕液與醋酸乙烯酯反應,生成乙酸一1一溴乙酯，滴加乙酸-1-溴乙酯(5)13.4g(0. 08mol),室溫反應5h,加氟比路芬與乙酸- -1-溴乙酯縮合,生成氟比洛芬酯。反應入200mL乙酸乙酯稀釋,將反應液轉入分液漏斗中,用3%條件溫和,每步收率良好,工藝穩(wěn)定.碳酸鈉詵滌(2X 200mL),分取有機層,無水硫酸鈉干燥,過參考文獻濾除去干燥劑，加人活性炭回流脫色20min,過濾除去活性[1]Liposomal Flurbiprofen Axtil. Drugs of the Future 1992,17(9),炎,將濾液常壓濃縮至無液體餾出,將剩余物減壓蒸餾，收集788~790.173~175C /0. 8mmHg餾分,得無色液體13. 8g,氟比洛芬[2]李述文,范如霖。實用有機化學手冊。上學科學技術出版社.1981年12月第1版,552.酯收率83.7%.[3]李長壽,尹魯生,范俊源,等。漠化氬- -冰乙酸制備方法的改進.3討論化學試劑,992,14(3)188此縮合反應的底物除乙酸-1-溴丙酯外.還可以使用[4]Hong You Wha, Shin Yaung Chul. A proces for the preparaion乙酸-1-氯乙酯和亞乙基二乙酸酯。反應歷程為氟比洛芬of 1- bromnoethylacethyl acetate. WO9855445.分子中羧基上的一0H進攻此三者連有鹵原子或乙酰氧基[5]Mimura Misuo,Uchida Katsuhiro, Production of 1- actoxethr的碳原子,而鹵原子或乙酰氧基離去.屬于Snz歷程的親核yI- 2- (2iluoro- 4- biphenylyl)propionate. . JP1211550.取代反應,所以離去基團的堿性對反應速度和反應條件至關醫(yī)藥中間體茄尼醇的體外抗菌活性研究陳保漢，張君'，余荷秀,胡慶利”(浙江永寧制藥廠，浙江黃巖318020; 1杭州奧默醫(yī)藥技術有限公司。浙江杭州30011;2臨邑縣醫(yī)藥公司,山東臨邑251500)摘要:目的研究從廢棄的煙草葉申提取純化后的醫(yī)藥中間體茄尼醇,對莘蘭陰性和革 蘭陽性菌的體外抗菌活性。方法采用瓊脂擴歉法和兩倍稀釋法考察茄尼醇對多種標準菌株和臨床分離菌株的抗菌活性。結果與緒論茄尼醇對被測菌株中的革蘭陰性菌(大腸埃希氏菌和銅縹假單胞酋)和革蘭陽性菌(金黃色葡萄球菌和蘋分枝桿菌)具有顯著的抗菌活性,而對枯草桿菌和環(huán)狀芽孢桿蘺活性較弱。關鍵詞:茄尼醇抗菌活性 煙草葉(茄科煙草屬)中圖分類號:R965.2文獻標識碼:A 文章編號 :1672- 7738(2007)09 - 0558- 02In Vitro Study on the Antibacterial Activities of a Medicinal Intermediate , SolanesolCHEN Bao-han, ZHANG Jun' , YU He xiu, HU Qingli(Zhejiang Yongning Pharmaceutical Factory, Huangyan 318020;L. Hangzhou Aome Medical Teechnology CompanyLimited, Hangzhou 310011;2. linyi county medicine company,Linyi 25150)ABSTRACT:OBJECTIVE Solanesol, purified from abandoned tobacco leaf, is an important medicinal intermediate. Ouraim of this study was to observe the antibacterial effect of solanesol against the gram- negative and gram - positive bacteri-a. METHODS Two classic methods, broth dilution and two- fold dilution. were employed to examine the activities of solane-sol on several standard strains and those collected from clinical patientclanesol demonstratedsignificant antibacterial activities ageinst all of the gram- negative (Esc中國煤化工。uginosa) and most ofthe gram- positive bacteria (Staphylococcus aureus and Mycobacterium:YHCNMHGteswereshownforthe two strains , Baillus subilis and Bacillus circulans.KEY WORDS:Solanesol,antibacterial activity ; tobacco leaves (Nicotiana tabacum L)