Polycyclic hydroxyquinones. 28. Synthesis and Diels-Alder reactions of N,N,O-triacyl derivatives of 10-amino-9-hydroxy-1,4-anthraquinones. An efficient, regiospecific synthesis of (±)-5-iminodaunomycinone, (±)-4-demethoxy-5-iminodaunomycinone, and (±)-daunomycinone

The development of a general strategy for the construction of anthracyclinones based on a Diels-Alder reaction of substituted derivatives of 10-amino-9-hydroxy-1,4-anthraquinone is described. The key stages are (i) formation of N,O,O-triacyl derivatives of 1,4-dihydroxy-9,10-anthraquinone monoimines in a tautomer specific fashion, (ii) transacylation into N,N,O-triacyl derivatives of the corresponding 10-amino-9-hydroxy-l,4-anthraquinone, and (iii) Diels-Alder reaction with an appropriately substituted 1,3-diene regiocontrolled by steric factors. This strategy has been applied to the total synthesis of (±)-5-iminodaunomycinone (4) and (±)-4-demethoxy-5-iminodaunomycinone (3) and to a novel and short synthesis of (±)-daunomycinone (5). © 1993 American Chemical Society.Financial support from the Secretaría de Estado de Universidades e Investigación (DGI- CYT Grants PB86-0627 and PB90-0072) and the Ministerio de Eduación y Ciencia (Fellowships to P.N.) are gratefully acknowledged.Peer Reviewe