The Structure of Showdomycin, a Novel Carbon-linked Nutcleoside Antibiotic Rela Ted to Uridine*

Showdomycin was first isolated from Streptomyces showdoensis by Nishimura and co-workers.1 It is a white crystalline antibotic of empirical formula C9H11N06 which is active against both gram-positive and gram-negative bacteria and is especially active against Streptococcus hemolyticus' and Streptococcus pyogenes.2 Showdomycin possesses significant antitumor activity against Ehrlich mouse ascites tumor in vivo and is active against cultured HeLa cells.3 It has a melting point of 153-1540C, a specific rotation of [a]22.5 + 49.90 (C = 1, H20), and a major ultraviolet absorption maximum of 220 mqu in aqueous solution.1 Antibiotic MSD-125A was obtained4 from Merck, Sharp and Dohme Research Laboratories, and a rigorous comparison of physical data indicated MSD-125A to be identical to showdomycin. The ultraviolet absorption spectrum of showdomycin' was suggestive of a maleimide-type structure. Treatment of showdomycin with dilute aqueous ammonia produced an absorption maximum at 328 mgu which rapidly disappeared upon further exposure to base. Similar behavior was exhibited with maleimide and is interpreted as a removal of the -NH proton by the base followed by basic hydrolysis to give ring opening. Table 1 illustrates the effect of dilute aqueous ammonia on showdomycin and certain maleimides. Inspection of Table 1 indicates the similarity of maleimide and showdomycin and strongly suggests the presence of hydrogen on the nitrogen atom. Determination of the pKa by the potentiometric method gave a value of 9.29 d 0.04 for showdomycin. Similarly, determination of the pKa of maleimide by the same procedure5 gave a value of 9.46 + 0.03. These data are again strong support for the imide-type structure and the presence of an acidic "NH"-type proton. The infrared spectrum of showdomycin' exhibits a very strong carbonyl band at 1704 cm-' which is very similar to that exhibited by maleimide at 1704 cm-'. Showdomycin was hydrogenated using palladium -on carbon catalyst and was found to consume 1.1 moles of hydrogen in ten minutes with loss of ultraviolet absorption. Maleimide under similar conditions absorbed 1.0 mole of hydrogen in six minutes with similar loss of ultraviolet absorption. Examination of the proton magnetic resonance spectra of showdomycin revealed a number of interesting features. (1) In dry deuterated dimethylsulfoxide-d6 a definite single absorption peak (one proton) was noted at 10.786, typical of the "NH" proton of a cyclic amide. A sharp doublet (one proton) was observed at 6.746, typical of an aromatic or vinylic proton. The remaining nine protons were observed as multiplets in the 3.2-5.346 region. (2) When showdomycin was examined in deuterium oxide in the presence of deuterated acetic acid-d4 (Fig. 1), the "NH" proton at 10.786 was absent due to deuterium exchange. Similarly, three protons previously found in the 3.2-5.36