ChemInform Abstract: Asymmetric Synthesis and DNA Intercalation of (-)-6-(((Aminoalkyl)oxy) methyl)-4-demethoxy-6,7-dideoxydaunomycinones.

✍ Scribed by Z. DIENES; P. VOGEL

• Publisher: John Wiley and Sons
• Year: 2010
• Weight: 35 KB
• Volume: 28
• Category: Article
• ISSN: 0931-7597
• DOI: 10.1002/chin.199705298

✦ Synopsis

Asymmetric

Synthesis and DNA Intercalation of (-)-6-(((Aminoalkyl)oxy) methyl)-4-demethoxy-6,7dideoxydaunomycinones.

-Asymmetric BF3•Et2O promoted Diels-Alder addition of (I) with ( II) gives the best diastereoselectivity to lead to one major monoadduct. This is added to in situ generated didehydrobenzene and converted to (VI) which can be transformed into (VIII). The latter compound (VIII) is used to construct the title compounds (IX). Absorbance and fluorescence titration experiments show the compounds ( IXa) and (IXb) to intercalate calf thymus DNA whereas (IXc) and (IXd) do not. The best intercalator is (IXb). Only compounds that are calf thymus DNA intercalators are inhibitors of human topisomerase II-induced DNA strand religation.