8736. Sparsomycin

Nomenclature

CAS number: 1404-64-4
(2E)-N-[(1S)-1-(Hydroxymethyl)-2-[(R)-[(methylthio)methyl]sulfinyl]ethyl]-3-(1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidinyl)-2-propenamide; (E)-(1S)-1,2,3,4-tetrahydro-N-[1-(hydroxymethyl)-2-[[(methylthio)methyl]sulfinyl]ethyl]-6-methyl-2,4-dioxo-5-pyrimidineacrylamide; (+)-sparsomycin; NSC-59729; U-19183.
C13H19N3O5S2; mol wt 361.44.
C 43.20%, H 5.30%, N 11.63%, O 22.13%, S 17.74%.

Description and references

Protein synthesis inhibitor with antibiotic and antitumor activity. Isoln from fermentation broth of Streptomyces sparsogenes var sparsogenes: S. P. Owen et al., Antimicrob. Agents Chemother. 1962, 772; GB 974541 (1964 to Upjohn); from S. cuspidosporus: E. Higashide et al., Takeda Kenkyusho Nempo 25, 1 (1966), C.A. 66, 54238q (1967). Characterization and purification: A. D. Argoudelis, R. R. Herr, Antimicrob. Agents Chemother. 1962, 780. Structural elucidation: P. F. Wiley, F. A. MacKellar, J. Org. Chem. 41, 1858 (1976). Total synthesis: H. C. J. Ottenheijm et al., ibid. 46, 3273 (1981); R. M. J. Liskamp et al., ibid. 5408. HPLC determn in plasma and urine: B. Winograd et al., J. Chromatogr. 275, 145 (1983). Pharmacokinetics and toxicology: Z. Zylicz et al., Cancer Chemother. Pharmacol. 20, 115 (1987). Ribosomal binding studies: E. Lazaro et al., Antimicrob. Agents Chemother. 35, 10 (1991). Biosynthetic studies: R. J. Parry et al., J. Am. Chem. Soc. 114, 5946 (1992). Review of chemistry and biological activity: H. C. J. Ottenheijm et al., Prog. Med. Chem. 23, 220-268 (1986).

Chemical structure

Properties

Crystals, mp 208-209° (dec). [α]D25 +69° (c = 0.5 in water). pKa′ 8.67 in water, 9.05 in 40% ethanol. uv max: 302 nm (water or 0.1N aq sulfuric acid), 328 nm (0.1N aq potassium hydroxide). Slightly sol in water and lower alcohols. Insol in less polar organic solvents. LD50 in dogs, rats, mice (mg/kg): 0.5-1.0, 2.25, 4.32 i.v. (Ottenheijm, 1986). LD50 i.p. in mice: 2.4 mg/kg (Owen).

Use

Research tool for studying protein biosynthesis.