Morley John O, Furlong Patrick J
Chemistry Department, University of Wales Swansea, Singleton Park, Swansea, UK SA2 8PP.
Org Biomol Chem. 2006 Nov 7;4(21):4005-14. doi: 10.1039/b610625k. Epub 2006 Oct 2.
The synthesis of a number of 1,4-bis(amino)anthracene-9,10-diones containing chlorine or sulfur which are related to the anti-cancer drugs Ametantrone and Mitoxantrone are reported. 1,4-Dichloro-2,3-dihydro-5,8-dihydroxyanthracene-9,10-dione reacts readily with a series of alkylamines to yield the corresponding 1,4-bis(alkylamino)-5,8-dichloroanthracene-9,10-dione after oxidation. The subsequent reaction of the products with ethanethiol or thiophenol gives the corresponding 1,4-bis(alkylamino)-5,8-bis(sulfanyl)anthracene-9,10-dione in good yield. Theoretical calculations at the RHF 6-31G** level indicate that the introduction of either chlorine or the phenylsulfanyl group into the 5- and 8-positions of 1,4-bis(alkylamino)anthracene-9,10-diones results in a lowering of the LUMO energies suggesting that related functionalised derivatives might have lower cardiotoxicities than Mitoxantrone.
报道了一些与抗癌药物氨茴环磷和米托蒽醌相关的含氯或硫的1,4 - 双（氨基）蒽 - 9,10 - 二酮的合成。1,4 - 二氯 - 2,3 - 二氢 - 5,8 - 二羟基蒽 - 9,10 - 二酮与一系列烷基胺容易反应，氧化后生成相应的1,4 - 双（烷基氨基）- 5,8 - 二氯蒽 - 9,10 - 二酮。产物随后与乙硫醇或苯硫酚反应，以良好的产率得到相应的1,4 - 双（烷基氨基）- 5,8 - 双（硫烷基）蒽 - 9,10 - 二酮。在RHF 6 - 31G**水平上的理论计算表明，在1,4 - 双（烷基氨基）蒽 - 9,10 - 二酮的5 - 和8 - 位引入氯或苯硫烷基会导致最低未占分子轨道（LUMO）能量降低，这表明相关的功能化衍生物可能比米托蒽醌具有更低的心脏毒性。
