6722. Novobiocin

Nomenclature

CAS number: 303-81-1
N-[7-[[3-O-(Aminocarbonyl)-6-deoxy-5-C-methyl-4-O-methyl-β-l-lyxo-hexopyranosyl]oxy]-4-hydroxy-8-methyl-2-oxo-2H-1-benzopyran-3-yl]-4-hydroxy-3-(3-methyl-2-butenyl)benzamide; crystallinic acid; streptonivicin; PA-93; U-6591.
C31H36N2O11; mol wt 612.62.
C 60.78%, H 5.92%, N 4.57%, O 28.73%.

Description and references

Antibiotic substance produced by Streptomyces spheroides: Kaczka et al., J. Am. Chem. Soc. 77, 6404 (1955); Wolf, US 3000873 (1961 to Merck & Co.); Stammer, Miller; Miller; Wallick, US 3049475; US 3049476; US 3049534 (all 1962 to Merck & Co.). By Streptomyces niveus: Hoeksema et al., J. Am. Chem. Soc. 77, 6710 (1955); Antibiot. Chemother. 6, 143 (1956); French, US 3068221 (1962 to Upjohn). Structure: Shunk et al., J. Am. Chem. Soc. 78, 1770 (1956); Hoeksema et al., ibid. 2019; Walton et al., ibid. 82, 1489 (1960). Conformation: Golding, Richards, Chem. Ind. (London) 1963, 1081. Revised configuration: O. Achmatowicz et al., Tetrahedron 32, 1051 (1976). Synthesis: Stammer, US 2925411 (1960); Walton, Spencer, US 2966484 (1960 to Merck & Co.); Vaterlaus et al., Helv. Chim. Acta 47, 390 (1964). Conversion of isonovobiocin to novobiocin: Caron et al., US 2983723 (1961 to Upjohn). Antiviral activity: Chang, Weinstein, Antimicrob. Agents Chemother. 1970, 165. Efficacy in canine respiratory infections: B. W. Maxey, Vet. Med. Small Anim. Clin. 75, 89 (1980). Mechanism of action studies: Smith, Davis, J. Bacteriol. 93, 71 (1967); H. T. Wright et al., Science 213, 455 (1981); I. W. Althaus et al., J. Antibiot. 41, 373 (1988). Review: Brock in Antibiotics vol. 1, R. Gottlieb, P. Shaw, Eds. (Springer-Verlag, New York, 1967) pp 651-665; M. J. Ryan, ibid. vol. 5(pt. 1), F. E. Hahn, Ed. (1979) pp 214-234.

Chemical structure

Properties

Pale yellow orthorhombic crystals from ethanol. Sensitive to light. d 1.3448. Dec at 152-156° (a rarer modification dec 174-178°). Acid reaction: pKa1 4.3; pKa2 9.1. [α]D24 -63.0° (c = 1 in ethanol). uv max (0.1N NaOH; 0.1N methanolic HCl; pH 7 phosphate buffer): 307; 324; 390 nm (E1%1cm 600, 390, 350 resp.). Sol in aq soln above pH 7.5. Practically insol in more acidic solns. Sol in acetone, ethyl acetate, amyl acetate, lower alcohols, pyridine. Additional soly data: Weiss et al., Antibiot. Chemother. 7, 374 (1957).

Derivative

Monosodium salt.

Nomenclature

CAS number: 1476-53-5
Albamycin (Pharmacia & Upjohn).
C31H35N2NaO11; mol wt 634.61.
C 58.67%, H 5.56%, N 4.41%, Na 3.62%, O 27.73%.

Properties

Minute crystals, dec 220°. [α]D24 -38° (c = 2.5 in 95% ethanol); [α]D24 -33° (c = 2.5 in water). Freely sol in water. A 100 mg/ml soln has a pH of 7.5 and a half-life of ≈30 days at 25° and several months at 4°. Soly data: Weiss et al., loc. cit. Properties: Birlova, Traktenberg, Antibiotiki 13, 997 (1968).

Therapeutic Category

Antibacterial.

Therapeutic Category (Veterinary)

Antimicrobial.