Synthesis and calculated properties of some 1,4-bis(amino)anthracene-9,10-diones.
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.
Morley
John O
JO
Chemistry Department, University of Wales Swansea, Singleton Park, Swansea, UK SA2 8PP.
Furlong
Patrick J
PJ
D000586:Amination; D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry*; D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010084:Oxidation-Reduction; D055672:Static Electricity; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013816:Thermodynamics
D000873:Anthracenes; D000880:Anthraquinones; D013438:Sulfhydryl Compounds; C042834:9,10-anthraquinone