6441. Negamycin

Nomenclature

CAS number: 33404-78-3
3,6-Diamino-2,3,4,6-tetradeoxy-l-threo-hexonic acid 2-(carboxymethyl)-2-methylhydrazide; 3,6-diamino-5-hydroxyhexanoic acid 2-(carboxymethyl)-2-methylhydrazide; [2-(3,6-diamino-5-hydroxy-1-oxohexyl)-1-methylhydrazino]acetic acid.
C9H20N4O4; mol wt 248.28.
C 43.54%, H 8.12%, N 22.57%, O 25.78%.

Description and references

Hydrazide antibiotic isolated from strains related to Streptomyces purpeofuscus: Hamada et al., J. Antibiot. 23, 170 (1970). Prepn: H. Umezawa et al., ZA 7002933; eidem, US 3679742 (1970, 1972 both to Microbiochem. Res. Found.). Structure and partial synthesis: Kondo et al., J. Am. Chem. Soc. 93, 6305 (1971). Total synthesis of negamycin and its antipode: Shibahara et al., ibid. 94, 4353 (1972). Synthesis of racemic negamycin: W. Streicher et al., J. Antibiot. 31, 725 (1978); G. Pasquet et al., Tetrahedron Lett. 21, 931 (1980); A. Pierdet et al., Tetrahedron 36, 1763 (1980). Stereocontrolled synthesis of (+)-negamycin: Y. F. Wang et al., J. Am. Chem. Soc. 104, 6465 (1982); S. DeBernardo et al., Tetrahedron Lett. 29, 4077 (1988). Mechanism of action: Mizuno et al., J. Antibiot. 23, 581 (1970); Y. Uehara et al., Biochim. Biophys. Acta 442, 251 (1976).

Chemical structure

Properties

Colorless powder, mp 110-120° (dec). [α]D29 +2.5° (c = 2). Amphoteric compound. pKa values after treatment with HCl-methanol: 3.55, 8.10, 9.75. Sol in water. Practically insol in methanol, ethanol, butanol, ethyl acetate, chloroform and benzene. LD50 i.v. in mice: 400-500 mg/kg (Hameda).

Therapeutic Category

Antibacterial.