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*2018－10-121968-。75000214-50℃~60℃80%35℃~45℃3.5h99.73%0.2%。TQ463.5A1673-5285201811-0115-05DOI:10.3969/j.issn.1673-5285.2018.11.029ThesynthesismethodofhighpurityepalrestatLIUXianghongYANGYajunLIZhaolinLIUXuNingxiaKangyaPharmaceuticalCo.Ltd.YinchuanNingxia750002ChinaAbstract:Thecrudeproductofepalrestatwassynthesizedonthebasisoftheliterature.Thecrudeepalrestatwasdissolvedin1,4-dioxaneunderthelightandthenfiltered.Thefiltratewascooledto50℃~60℃,80%aqueousmethanolwasadded.Thepurifiedepalrestatwasfiltratedafter3.5hincubationat35℃~45℃.Thepurityoftheobtainedepalrestatwas99.73%,andtheisomerimpuritieswasbelow0.2%.Keywordsepalrestataldosereductasepurifyepalrestat15-1Z2E-2--3--2--4--2--3-1992、、、、、[12]1。1Fig.1Structuralformulaofepalrestat[3]3-α-。[4]、N-、3-α-。3-80%60%48%。[5]“”、N-PETROCHEMICALINDUSTRYAPPLICATION3711201811Vol.37No.11Nov.2018、3-α-。3-85.3%64%54.6%。[6]、N-、3-α-。3-86.0%85.2%73.3%。、N-、3-α-2。、2Z-0.5%0.2%[7]。。14-50℃~60℃80%35℃~45℃3.5h0.2%。100L。11.1《》20150512-0.4%62:38396nm1mL/min30℃。1.220mg50mL15mL1mL100mL20μL20%20μL2~31.00.65~0.871.51.5%。1.311000mL50.0g800mL98%30min55℃4h50℃8h21.6g92.18%343.2%。1.421000mL50.0g500mL2Fig.2Syntheticrouteofepalrestat2018371163Fig.3TheHPLCspectrumofformicacidrefinedepalrestat45℃～50℃4h50℃8h36.0g92.18%472.0%。1.531000mL98.7g14-200mL50℃~60℃780mL80%35℃~45℃3.5h50403020100/mV05101520253035404550556065/minNo.RT1BC13.3257180.038BV23.5313260.009VB34.7217760.012BB46.8252200.034BB57.7163690.042BB612.49102290.067BB716.0724520.016BB817.1967140.044BB920.0111516817.556BB1022.251405121192.183BV15242696100.00050403020100/mV05101520253035404550556065/min111175Fig.5TheHPLCspectrumofrefinedepalrestat4Fig.4TheHPLCspectrumoftetrahydrofuranrefinedepalrestatNo.RT1BC14.0045410.026BB24.633640.002BB35.048630.005BB45.7529550.017BB56.49235980.137BB69.94143860.083BB711.51192350.111BB812.6032010.019BB913.3382000.047BB1015.2510896456.305BV1116.771608486893.069VB1229.2010850.006BB1338.35257610.149BB1444.249470.005BB1545.4931060.018BB17282755100.00050403020100/mV05101520253035404550556065/minNo.RT1BC15.37084420.006BB29.50369450.005BB311.5536050.000BB411.95384310.006BB514.2202326630.178BV616.2601.304E+0899.729VB730.68717740.001BB833.067116550.009BB943.383844200.065BB1.307E+08100.00020183711820163551028-1036.2．J．2016364119-128.3．J．201234618-22.4．-J．200810419-21.5．J．201229617-20.6．J．201524216-18.7．J．200926260-62.8．3-3J．2016385612-616.9．-J．201139281-85.10．J．200825557-60.11．J．199315353-56.12．J．20001741-3.13．J．19963650-53.14．J．2015121451-54.15EM.．M．．1985.16．J．2014291261-270.17．ANSYSJ．2011222340-346.10mL×350℃8h79.5g99.73%580.5%。225℃~227℃。214-50℃~60℃80%35℃~45℃3.5h99.7%0.2%。。1SteeleJWFauldsDGoaKLetal.Epalrestatareviewofitspharmacologyandtherapeuticpotentialinlateonsetcom－plicationsofdiabetesmellitusJ.DrugsAging199336532-535.2.M.:1996.3.5-1Z2E-2--3--2--4--2--3-P.JP2004-210702A.4.J.2001113165-167.5.J.1995184413-416.6.J.2003324356-358.7.J.2012391141-42.83!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!11119