A useful extension of the Marschalk reaction directed toward synthesis of 11-deoxydoxorubicin antitumor antibiotics.

✍ Scribed by L.A. Mitscher; Tzay-Shiang Wu; Ish Khanna

• Publisher: Elsevier Science
• Year: 1983
• Tongue: French
• Weight: 205 KB
• Volume: 24
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)94013-9

✦ Synopsis

Diisopropylidine methylene dimalonate (g) has been developed as a useful reagent Kansas for the introduction of functionalized 3-carbon chains in otherwise deactivated monohydroxyanthraquinones and its utility is expanded to the synthesis of advanced intermediates of 11-deoxydoxorubicin analogues. The Marschalk reaction (Z_ + L), discovered in 1936, provides a useful means of adding carbon atoms and functionalized side-chains to certain otherwise highly deactivated anthraquinones. 1 It has recently been utilized effectively in preparation of synthons directed toward 4,6,11-and 6,11-hydroxylated anthracycline antibiotics (z).* With leucoquinizarin analogues (2, X=H) we, and others, have observed that two different side-chains can be added--if the side-chains are added in the appropriate sequence--to provide advanced functionalized tetracyclic intermediates (2). Whereas the original Marschalk reaction involved preferably highly reactive non-enolizable aldehydes, conjugate addition of acrylates and vinyl ketones can be accomplished within the scope of the common reaction conditions.2cg3s6 Recently a number of investigators have worked toward the synthesis of 11-deoxydoxorubicin analogues.4 The original Marschalk reaction1 demonstrated that 1-hydroxyanthraquinones were suitable substrates if highly reactive aldehydes were used as partners.

We found, however, that unacceptable yields are obtained in the conjugate