1202. Bicyclomycin

Nomenclature

CAS number: 38129-37-2
(1S,6R)-6-Hydroxy-5-methylene-1-[(1S,2S)-1,2,3-trihydroxy-2-methylpropyl]-2-oxa-7,9-diazabicyclo[4.2.2]decane-8,10-dione; bicozamycin; aizumycin; 8,10-diaza-6-hydroxy-5-methylene-1-(2-methyl-1,2,3-trihydroxypropyl)-2-oxabicyclo[4.2.2]decan-7,9-dione; antibiotic 5879; WS-4545 antibiotic.
C12H18N2O7; mol wt 302.28.
C 47.68%, H 6.00%, N 9.27%, O 37.05%.

Description and references

Structurally unique antibiotic; exhibits broad spectrum activity vs Gram-negative bacteria and the Gram-positive bacterium, Micrococcus luteus. Prepn by fermentation of Streptomyces sapporensis: T. Miyoshi et al., DE 2150593; H. Imanaka et al., US 3923790 (1972, 1975 both to Fujisawa). Isoln and characterization: T. Miyoshi et al., J. Antibiot. 25, 569 (1972). Isoln from S. aizunensis and identity with antibiotic 5879: S. Miyamura et al., ibid. 26, 479 (1973). Structural elucidation: T. Kamiya et al., ibid. 25, 576 (1972). Crystal and molecular structure: Y. Tokuma et al., Bull. Chem. Soc. Jpn. 47, 18 (1974). In vitro and in vivo activity studies: M. Nishida et al., J. Antibiot. 25, 582 (1972). Metabolism: eidem, ibid. 594. Total synthesis of (±)-bicyclomycin: S. Nakatsuka et al., Tetrahedron Lett. 24, 5627 (1983); of (+)-bicyclomycin: R. M. Williams et al., J. Am. Chem. Soc. 106, 5749 (1984); eidem, ibid. 107, 3253 (1985). Efficacy vs Shiga toxin-producing E. coli in calves: N. Misawa et al., Microbiol. Immunol. 44, 891 (2000). Review of synthetic, mechanistic and biological studies: R. M. Williams, C. A. Durham, Chem. Rev. 88, 511-540 (1988); of mechanism of action: H. Kohn, W. Widger, Curr. Drug Targets Infect. Disord. 5, 273-295 (2005).

Chemical structure

Properties

Monoclinic crystals from ethanol, mp 188-191° (dec); rhombic crystals from methanol + acetone, mp 187-189° (dec) (Imanaka), also reported as mp 166-170° (Nakatsuka et al.). [α]D23 +63.5° (methanol). Weakly basic substance. Soly in water: 192 mg/ml. Sol in methanol; sparingly sol in ethanol. Slightly sol in acetone. Practically insol in chloroform, ethyl acetate, benzene, n-hexane. Unstable in alkaline soln. LD50 orally, s.c., i.p. in mice: >4 g/kg (Williams, Durham).

Derivative

Benzoate.

Nomenclature

CAS number: 37134-40-0
Bicomarin (Schering-Plough).
C19H22N2O8; mol wt 406.39.
C 56.15%, H 5.46%, N 6.89%, O 31.50%.

Therapeutic Category (Veterinary)

Antibacterial; feed additive (livestock).