Daunomycinones

Friedel-Crafts reaction of i)-methoxyben2ene with y-butyrolactone gives the dimethoxytetralone, which serves as an intermediate for anthracyclinones, such as daunomycinone [21794-55-8J (96). 

Daunomycinone derivatives Demethylation Corresponding demethylated Carminomycinone derivatives Sepedonlum chrysospermum Beauveria sulfurescens... 

Similar results are obtained with the /htetralone derivatives 12, which are useful building blocks in the synthesis of anthracycline antibiotics. Furthermore, the usefulness of the diastereoselec-tive addition to ot-oxo acetals was impressively demonstrated in the synthesis of (-)-7-deoxy-daunomycinone, which uses the completely stereoselective addition of (trimethylsi-lylethynyl)magnesium chloride to the /i-tetraione acetal 12 (R =OMOM R2 = Br) as the key reaction31. 

Scheme 40 Benzannulation towards daunomycinone based on ring B formation...

Replacing a hydroxy group in daunomycinone by a hydrogen atom leads to 11-deoxydaunomycinone 79. However, this formally simple transformation affords a fundamental change of the synthetic strategy. Two very similar syn-... 

Syntheses and antitumor activities of 7-0-(2,6-dideoxy-2-fluoro-o -L-ta-lopyranosyO-daunomycinone and -adriamycinone, T. Tsuchiya, Y. Ta-kagi, K. Ok, S. Umezawa, T. Takeuchi, N. Wako, and H. Umezawa, J. Antibiot., 39 (1986) 731-733. 

Substituted quinone ketals, prepared in this manner, serve nicely in annelation strategies leading to natural products. Two are illustrated, one in Scheme 20 leading to (+)-4-demethoxydaunomycinone (87) and (+)-daunomycinone (88) [46-48], the other in Scheme 21 serving as a pathway to a-citromycinone (94). The first calls for a Michael addition of (84) to quinone ketal (83) followed by capture of the intermediate enolate, and leads to annelated... 

Antkracyclinones. A key step in a stereocontrolled synthesis of 4-demethoxy-daunomycinone (4) involves cycloaddition of the epoxide 1 with this diene (2). Later steps follow known transformations. 

This methodology provides a regiocontrolled synthesis of anthracyclinones such as daunomycinone (2) as outlined in Scheme (I).3... 

Daunomycinone, 254, 255 Debenzylation, 532 Debromination, 276, 548, 599 Decarboalkoxylation, 301 Decarboraethoxynauclechine. 185 Decarbonylation, 393 Decarboxylation-carbonylation, 392 Dehydroamination, 502 Dehydroamino acids, 6-7 Dehydrocyanation, 173 Dehydrosulfiiration, 62 Dehydroxylation, 127 Dendrobatid toxins, 43 Dendrolasin, 419 Denitration, 547 Deoxoprosophylline, 315 11-Deoxyanthracycline, 113 11-Deoxydauomycinone, 85 Dcoxyfrenolicin, 357 14-Deoxymuristerone, 127... 

The mechanism of glycal addition was further examined by Horton and coworkers,86 who have used this method to form (7S,9S)-4-demethoxy-7-0-(2,6-dideoxy-2-iodo-a-L-mannopyranosyl)-adriamycinone87 and -daunomycinone,88 which are iodinated analogs of natural antitumor compounds. The nature of the solvent was found to be critical. In particular, they were able to generalize that in non-coordinating polar solvents, where no possibility for interaction with iodine exists—that is, no lone-pair interactions—the formation of the iodonium intermediate was irreversible, and the resultant stereochemistry reflects the electronic... 

For a review of synthetic strategies towards daunomycinone, see P. J. Harrington, Transition Metals in Total Synthesis, Wiley, New York, 1990, pp. 346-399. 

---