| The aim of this dissertation is efficient synthesis of a novel direct angiogenesis inhibitor Bryoanthrathiophene and its analogs.The 1,8-dihydroxyl-9,10-anthraquinone was used as the cheap and common starting material.First of all,the key intermediate 5,7-dihydroxy-1- methoxycarbonyl-6-oxo-6H-anthra [1,9-bc]thiophene was synthesized through 5 steps including protecting,nitration,methyl mercaptoacetate substitution,intramolecular Aldor reaction and deprotecting in the total yield of 45.8%using 1,8-dihydroxy-9,10-anthrathiophene as staring material and regioselective nitration of mix acid(H2SO4-HNO3) as key step.Secondly,the natural product 5,7-dihydroxy-1-hydroxymethyl-6-oxo-6H-anthra[1,9-b c]thiophene was synthesized from 1,8-dihydroxyl-9,10-anthraquinonein the total yield of 37%using 5,7-dihydroxy-1-methoxycarbonyl-6-oxo-6H-anthra[1,9-bc]thiophene as key intermediate and chemoselective reduction of NaBH4-MeOH as key step.Thirdly,Bryoanthrathiophene was synthesized in 5 steps from 1,8-dihydroxyl-9,10-anthraquinone in the total yield of 31.7%using 5,7-dihydroxy-1-hydroxymethyl-6-oxo-6H -anthra[1,9-bc]thiophene as key precusor and reduction of Zn-HOAcas the key step.Fourthly,biosimulation synthesis of Bryoanthrathiophene was achieved through oxidation from 5,7-dihydroxy-1-hydroxymethyl-6-oxo-6H-anthra[1,9-bc]thiophene.Finally,5,7-dihydroxy-6-oxo-6H-anthra[1,9-bc]thiophene was synthesized through reduction of 5,7-dihydroxy-1-methoxycarbonyl-6-oxo-6H-anthra[1,9-bc]thiophene by Zn-HO Ac.In summary,the novel direct angiogenesis inhibitor Bryoanthrathiophene and its 1-hydormethyl,1-hydrogen,1-aldehyde analogues were first efficiently synthesized and these antiangiogenenic activity is in the process. |
