[生物醫(yī)藥論文精品a]脂質(zhì)體輔料二硬脂酰磷脂酰乙醇胺的合成研究

脂質(zhì)體輔料二硬脂酰磷脂酰乙醇胺的合成研究吳立紅，張宏武，鄭利剛，劉亞英A1A2A0A3A4A5A6A7A0A8A9A1A2A10A11A13A14A12A15A16A18A2A10A11050051A13A17A19A20A21A22A23A24A25A26A27A28A29A30A31A32A33A28A34A35A36A37A22A38A39A40A41A42A43A44A45A46A47A48A49A36A50A51A52A53A32A18A54A55A56A57A58A59A60A61A59A62A53A59A63A64A57A58A59A65A66A59A67A61A59A68A66A59A33A34A61A69A7A70A71A72A42A73A74A21A75A61A38A76A54A29A77A78A79A80A68A77A81A82A18A83A84A85A50232A42A73A86A71A87A88A53A32A39A71A89A18A90A91A92A93A18A94A38A40A95A61A96A97A42A98A99A100A100A20A28A29A30A31A32A101A33A28A34A35A36A37A101A38A39A102A103A104A105A106A104A105A107R914A108A109A110A111A112A110A111A113ASTUDIESONSYNTHESISOFLIPOSOMEEXCIPIENT1,2STEAROYLPHOSPHATIDYLETHANOLAMINEWULIHONG,ZHANGHONGWU,ZHENGLIGANG,LIUYAYINGCSPCZHONGQIPHARMACEUTICALTECHNOLOGYSJZCOLTD,SHIJIAZHUANG050051ABSTRACTA113OBJECTIVETOSTUDYANDIMPROVETHESYNTHESISOFLIPOSOMEEXCIPIENTPHOSPHATIDYLETHANOLAMINEA114METHODSPHOSPHATIDYLETHANOLAMINEWASPREPAREDFROMDMANNITOLBYISOPROPYLIDENDANDOXYGENATION,REDUCTION,FOLLOWEDBYBENZYLATION,HYDROLYSIS,ESTERIFICATION,HYDROGENOLYSISANDPHOSPHORYLATIONA114RESULTSTHESTRUCTUREOFTARGETCOMPOUNDWASIDENTIFIEDBYMSAND1HNMRA114THEOVERALLYIELDWAS232A115A114CONCLUSIONTHISCOSTSAVINGANDSIMPLIFIEDMETHODCANBEUSEDINTHEINDUSTRIALPREPARATIONA114KEYWORDSA113LIPOSOMEEXCIPIENTA116PHOSPHATIDYLETHANOLAMINEA116SYNTHESIS二硬脂酰磷脂酰乙醇胺（DSPE），化學名1,2二硬脂酰SN甘油醇3磷脂酰乙醇胺，屬于合成磷脂，由于磷脂具有兩親性既有親水性又有親脂性，分散在水中可以形成雙分子層結(jié)構，利用該性質(zhì)發(fā)展了一種新技術脂質(zhì)體。近年來脂質(zhì)體作為靶向給藥系統(tǒng)新劑型，在制劑新技術研究中受到廣泛關注。由于天然磷脂具有易氧化、不穩(wěn)定的缺點，使得合成磷脂在脂質(zhì)體研究和應用中起著重要作用。合成磷脂中應用最多的是磷脂酰乙醇胺和磷脂酰膽堿，全世界只有G1972G4490可以G17839G15904G10995G1147，G11458G2081G3281G1881G4590G7422G4466G10628G17837G1135G2709種的G1147G1006化。G3G7003G10498A117A118A119A120A121G6265G17959的二硬脂酰磷脂酰乙醇胺的合成G17347G13459是以的D甘G19718醇為起G3999G2419G7021，G13475G17819G1005G2461G1457G6264、氧化G17836G2419、G14488G3534G1457G6264、水G16311、G18243化、G14085G14488、磷酰化G12573多G8505G2465G3G3G3G3G3G3G3G3G3G3G3G3G3G3G3G3G3G3G3A122A123A124A125A126A127A128A129A130A131A132A133A134A135A136A137A138A124A125A139A140A142應G10995成G11458G7643化合G10301，G6117G1216在G2454G13783G8504G7003G10498的G3534G11796G990，G4557G5049G14414G7477G1226G17839G15904了G1260化，G1866中在G14488G3534化G2465應中用G7092G7438堿G7379G1207了G5390堿，使G2530G3800G10714G7368為G12628G2345，G2528G7114G10995成的G1147G10301不G19668G12946G20323，可G11464G6521用于G991一G8505G727在G18243化G2465應中用G8614性G17751G4579的二G8707G11014G9931G6454G6493了G11458G2081G5062G13475G19492制使用的G14280G11296G9354劑G3247G8707化G11911，G8616G17751G17878合G5049G1006化G10995G1147G727在G8694化G2465應中，G6117G1216G17902G17819G6523制G9213G5242、G7114G19400G2462G2399G2159，G18003G1825了G5334構體的G10995成G727在磷酰化G2465應中，G6117G1216G17902G17819G1260化G5445G2721G3252G13044G4570G7003G10498A117A143A121中G989、G3247G8505G2465應G13565G11713為兩G8505，G12628化了G8505G20600，G19489G1314了成G7424。G6925G17839G2530的G17347G13459G5049G14414穩(wěn)定，G2419G7460G7021G2462G16809劑G5277G1227易得，G17878合G1147G1006化G10995G1147。具體合成G17347G13459G16277圖1。G3G3CH2OHOOHOOHOHOHOHOHOHHHHHOOOHOHOOHHHHBNCLC17H33COOHPOCL3OHCH2CH2NH2NABH4HCLNAIO4OHHOC17H33OOC17H33OOHOC17H33OOC17H33OPOOONH3OHOHOHOHOC17H33OOC17H33OACETONEH2/PB257346G3A144A145A146A147A148A149A150A151A149A152A153A154FIG1SYNTHESISROUTEOFTITLECOMPOUND1G3儀器與G7460G7021G3G3G3X4型數(shù)字顯微熔點測定儀，WZZ2A型自動旋光儀，AC300型核磁共振儀（G1881G7643TMS，G9354劑CDCI3），所用G16809劑均為G5049G1006級G32G3合成G17347G13459G321G31,2,5,6G5334亞G1005G3534D甘G19718醇（3）的合成500MLG1005酮中加入G8707化鋅（100G，073MOL），回流30MIN，加入D甘G19718醇（50G，027MOL）G2465應2H，然G2530加200ML飽和G8707化鈉G9354液，200MLG8707仿萃取2次，合并G2530加入5的氨水400ML洗滌，加G7092水硫酸鎂干燥，G17819濾、濃G13565G2530得白色固體（49G，681。），MP1151170C（G7003G10498值1171190C）。22G5334亞G1005G3534甘油醇（4）的合成G3在2700ML水中加入高碘酸鈉（899G，042MOL），G9354清G2530加G8694氧化鋰調(diào)PH值到6，G45703（36G，014MOLG9354于160MLG11014醇，G4570G11014醇G9354液滴加至G990述水G9354液中，G9213G5242G6523制在00C，G2465應2H，再加入8100MLG11014醇，G17819濾，濾液中加硼G8694化鈉423G，112MOL，00CG2465應50MIN，1500MLG8707仿萃取3次，G7092水硫酸鎂干燥，G17819濾，減G2399蒸G20323濃G13565G2530得到G7092色液體（289G，803），BP10MM77790C（G7003G10498值77780C）。233G14488G3534甘油醇（5）的合成在400MLG11014G3534乙G3534亞砜G9354液中加入416G，012MOL、G8694氧化鉀134G，024MOL、G8707化G14488（38G，03MOL），室G9213G2465應45，加160ML純凈水，加160MLG11014G3534叔丁G3534醚萃取，濃G13565G2530得到的液體加200MLG11014醇，3N的鹽酸100ML加熱回流05H，65ML石油醚萃取1次，65ML乙酸乙G18243萃取2次，G7092水硫酸鎂干燥，濃G13565得到G7092色液體4（178G，809）,BP1MM1451470C（G7003G10498值1451460C）。243G14488G35341,2二硬脂酰甘油（6）的合成G45705（12G，006MOL）、硬脂酸（454G，016MOL、二環(huán)己G3534G11911二亞胺（152G，012MOL、4二G11014胺G3534吡啶（032G，0002MOLG9354于360ML二G8707G11014G9931中，G6523G9213300C攪拌15H，G17819濾，濾液濃G13565得白色固體，乙醇重結(jié)晶G2530得白色粉末5（312G，664），MP505050C（G7003G1049850510C）。251,2二硬脂酰甘油（7）的合成G3800MLG3247G8694呋喃中加入6（20G，003MOL，10鈀G11911（2G），G2399G2159為25MPA,G6523G9213600CG2465應G7114G194008H，置G6454G2530，G17819濾鈀G11911，濾液濃G13565得到白色粉末6，（168G，96）。MP747450C（G7003G10498745750C）。261,2二硬脂酰甘油磷脂酰乙醇胺（1）的合成150MLG3247G8694呋喃中加入7（10G，002MOL、G989G8707氧磷53G，003MOL、13MLG989乙胺，G6523G9213350C攪拌2H，G17819濾，濾液濃G13565G2530再加入80MLG3247G8694呋喃，乙醇胺245G，004MOL和10MLG989乙胺，G6523G9213G5242200C，G2465應15MIN，G17819濾，濾液濃G13565得白色固體。正己G9931重結(jié)晶得到白色粉末1（985G，823），MH7481，1HNMRCDCI3087T，6H，J67HZ，CH3，126M，56H，CH3CH214，157M，4H，CH3CH214CH2,，228M，4H，COCH2，336M，2H，CH2NH，394M，2H，CH2OP，417M，2H，GLYCEROL3CH2，439M，2H，GLYCEROL1CH2，520M，1H，GLYCEROL2CH，760（T，1H，NH）REFERENCESA155A156A157EIBLH,ANIMPROVEDMETHODFORTHEPREPARACTIONOF1,2ISOPROPYLIDENESNGLYCEROLJCHEMPHYSLIPIDS,1981,28A1581A15915A155A160A157EIBLH,WOOLLEYP,SYNTHESISOFENANTIOMERICALLYPUREGLYCERYLESTERSANDETHERSIMETHODSEMPLOYINGTHEPRECURSOR1,2ISOPROPYLIDENESNGLYCEROLJCHEM