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

Total synthesis of (±)-5-iminodaunomycinone and (±)-4-demethoxy-5-iminodaunomycinone

The total synthesis of (±)-5-iminodaunomycinone (4a) and (±)-4-demethoxy-5-iminodaunomycinone (4b) has been achieved from the readily available 5-methoxy-1,4-dihydroxy-9,10-anthraquinone (5a), and 1,4-dihydroxy-9,10-anthraquinone (5b), respectively. A short and convenient synthesis of (±)-daunomycinone (4c) has also been achieved by acid hydrolysis of 4a.Financial support from the Secretaria de Estado de Universidades e Investigación (DGICYT grant PB86-0627) is gratefully acknowledged.Peer Reviewe

Polycyclic hydroxyquinones. XXVII. Tautomerism in 1,4,-dihydroxy-9,10-anthraquinone monoimines. Cycloaddition reactions of their 1,4-anthraquinonoid tautomers

1,4-Dihydroxy-9,10-anthraquinone monoimine and differently substituted derivatives thereof (6a-i) have been preparad by ammonolysis of the corresponding 1,4-dihydroxy-9,10-anthraquinones. 1H- and 13C-n.m.r. studies show the existence of a rapid tautomeric equilibrium in quinone imines of type 6. Diels-Alder reaction with the 1,4-anthraquinonoid tautomer of quinone monoimines 6a,e affords ABCD tetracyclic systems related to those existing in anthracyclinones.Flcial support from the Secretarfa de Estado de Universidades e Investigación (DGICYT grant PB86-0627) and the Ministerlo de Eduación y Ciencia (Fellowships to P.N.) are gratefully acknowledged. We also thank Professor C. Pascual for obtaimng part of the n.m.r. spectra.Peer Reviewe

Quorum sensing network in clinical strains of A. baumannii : AidA is a new quorum quenching enzyme

Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2-clon-2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/β hydrolase gene, AidA). This QQ enzyme was present in all nonmotile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421-GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of HO (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/β hydrolase gene, AidA protein) was detected in these strains