Title: Bicozamycin
CAS Registry Number: 38129-37-2
Synonyms: Bicyclomycin; 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
Manufacturers' Codes: WS-4545 antibiotic
Trademarks: Bacfeed (Fujisawa)
Molecular Formula: C12H18N2O7
Molecular Weight: 302.28
Percent Composition: C 47.68%, H 6.00%, N 9.27%, O 37.05%
Literature References: Cyclic peptide antibiotic substance. 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). Bicyclomycin has a unique chemical structure which bears no relation to any group of known antibiotics. 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. Mechanism of action: N. Tanaka
et al., ibid. 29, 155 (1976); N. Tanaka in
Antibiotics vol. 5(pt. 1), E. Hahn, Ed. (Springer, New York, 1979) p 18. Synthetic approaches: L. V. Dunkerton, R. M. Ahmed,
Tetrahedron Lett. 21, 1803 (1980); R. M. Williams,
ibid. 22, 2341 (1981); S. Nakatsuka
et al., ibid. 4973; J. H. Hoare, P. Yates,
Chem. Commun. 1981, 1126. 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). Review of synthetic, mechanistic and biological studies: R. M. Williams, C. A. Durham,
Chem. Rev. 88, 511-540 (1988).
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.). [a]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 in mice: >4 g/kg (Williams, Durham).
Melting point: mp 188-191° (dec); mp 187-189° (dec) (Imanaka); mp 166-170° (Nakatsuka
et al.)
Optical Rotation: [a]D23 +63.5° (methanol)
Toxicity data: LD50 in mice: >4 g/kg (Williams, Durham)
Therap-Cat-Vet: Antibacterial; feed additive (livestock).
