《药物合成反应作业》PPT课件.pptx

TotalSynthesisofAmphirionin4-MichaelHolmes,DanielKwon,MatthewTaron,andRobertBritton演讲小组成员:陈人豪、王兴瑞、黄渊主讲人:-4”(附)ThereactionconditionsandrelatedmechanismAmphidiniumspeciesofmarinedinoflagellatesAmphidiniumspeciesofmarinedinoflagellateshaveproventobearichsourceofstructurallydiversepolyketides,1manyofwhicharecharacterizedbycyclicethersofvariousringsizesandpotentcytotoxicactivity(.,amphidinolideB2andamphidininA3).poundthatweneedtosynthesize。Ofparticularinterestisamphirionin-4(1),4awhichdemonstratesselectiveandpotentproliferationactivityonmurinebonemarrowstromalST-2cells(+950%).potentcytotoxicactivity具有很强的细胞毒性Amphidinium-4Structurecharacteristics:-stereocenterthepolyenesidechainRetrosyntheticAnalysisforAmphirionin-4(1)Thestructureofthreekeyintermediates三个关键的中间体的结构weenvisionedthreekeyretrosyntheticdisconnections(Scheme1).-13化合物12-,NaI,.rt(46%)2.(COCl)2,DMSO,Et3N,CH2Cl2(70%)-16合成目标中间体16,需要经过12-16这样一个过程。-14化合物13-(20mol%)NCS,CH2Cl2Macmilllan‘-,LDAthen14,-78℃,THF(78%)(OAc),AcOH,-40℃(79%),LDA,THF为醛和***(OAc)3为一个具有绝对构型的还原剂,使得羰基被还原成固定构型的羟基。