SYNTHESIS AND REDOX CHEMISTRY OF 5-DEOXYDAUNOMYCIN - A LONG-LIVED HYDROQUINONE TAUTOMER

Reduction of 5-iminodaunomycin with dithionite in anaerobic methanol f ollowed by lowering the pH to 3 and saturating with air led to deamina tion without glycosidic cleavage to yield 89% 5-deoxydaunomycin. An in termediate observed during the reaction is proposed to be the hydroqui none tautomer, 2-tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone hydr ochloride (1), which loses ammonia with a half-life of 49 min. Anaerob ic reduction of 5-deoxydaunomycin with bi(3,5,5-trimethyl-2-oxomorphol in-3-yl) (TM-3 dimer) in methanol buffered to an apparent pH of 8 yiel ded 26% recovered 5-deoxydaunomycin, 56% 5,7-dideoxydaunomycinone, and 18% -acetyl-11-hydroxy-7-methoxy-5,12-naphthacenedione (5) after 42 h and subsequent exposure to molecular oxygen. The reduction leads to r elatively rapid formation of a long-lived transient proposed to be, 2- tetrahydro-6,8,11-trihydroxy-5(8H)-naphthacenone (4). Exposure of 4 at its maximum concentration to molecular oxygen yielded 88% recovered 5 -deoxydaunomycin and 12% 5. Tetrahydronaphthacenone 4 disappeared with a half-life of 2283 min in the absence of oxygen and 16 min in air-sa turated methanol. Mechanistic pathways to the products are proposed in Scheme II. Analysis of the apparent rate constants for disappearance of 4 indicates that 5-deoxydaunomycin undergoes glycosidic cleavage to its 7-deoxyaglycon 8000 times slower than daunomycin upon reduction t o the hydroquinone state.