340 



DESCRIPTIONS OF ANTIBIOTICS 



bacteria and fungi. Active on tomato early blight 

 (greenhouse studies), tomato late blight, and 

 bean rust (1). Active on powdery mildew of pear 

 (Podosphaera leucotricha) in the greenhouse (2). 



Toxicity: Not toxic to tomato and bean plants 

 at therapeutic levels (1). 



References: 



1. Ziffer, J. S. et al. Phytopathology 47:539, 



1957. 



2. Sprague, R. Plant Disease Reptr. 42: 



1208-1209, 1958. 



Picroniycin 



Produced by: Strepiomyces felleus strains (2, 8, 

 18), Streptomyces spp. (2, 7, 16). 



Synonyjns: Argomycin (12), antibiotic BU 277 

 (18). Similar or identical to proactinomycin A 

 (13) and amaromycin (11). Griseomycin is 

 isomeric with picromycin (13). Differs from 

 methymycin only in point of attachment of the 

 desosamine to the lactone ring. 



Method of extraction: Concentrated broth, or an 

 aqueous solution of the residue of a concentrated 

 ethyl acetate extract of the broth, is extracted at 

 pH 9.0 with ether. Ether concentrated and re- 

 extracted into 0.1 A' HCl at pH 1 to 2 . Adjusted to 

 pH 9 to 10 with Na^COs , filtered, and extracted 

 with ether. Ether taken to dryness in vacuo. 

 Crystallized from acetone, boiling methanol, or 

 ethanol, or purified by salt conversion. Further 

 purification by fractional cUstribution and chroma- 

 tography (1, 2, 16). 



Chemical and phtisical properties: Macrolide. 

 Colorless, bitter-tasting crystals resembling 

 coffin-covers; m.p. 169-170°C. Very soluble in 

 acetone, benzene, chloroform, ethyl acetate, 

 dioxane, and dilute acids. Moderately soluble in 

 ether and cold methanol. Scarcely soluble in 

 water, petroleum ether, or carbon disulfide. Ultra- 

 violet absorption spectrum maxima at 222 (log 

 e = 4.02) and 293 ni/x (log e = 1.83) (15) or at 225 

 niM (log e = 3.97) (16). Infrared spectrum given in 

 reference 16. [af^ = -50.2° (c = 6.3 per cent in 

 chloroform) and +8.2° (c = 3.5 percent in ethanol). 

 Orange-red solution in concentrated H2SO4 gives 

 only end-absorption of ultraviolet light. This 

 color fades on dilution, giving a precipitate. 

 Positive KMn04 test in glacial acetic acid. Nega- 

 tive Isromine, ninhydrin, and p-nitrophenylhy- 

 drazine tests. Warming with dilute acid or alkali 

 destroys biological activity. C = 63.86%; H = 

 9.02%; N = 2.92%; N— CH3 = 4.0%; active H = 

 0.59%; CHs = 16.2%. Molecular weight, 458. 

 CsoH-isOtN. Picrate: Yellow. Amorphous hydro- 

 chloride andpicrolonate (1,2,5,8, \h). Quaternary 



salt with methyl iodide: Co^HoiNOsI; m.p. 193-195° C 

 [«],> = 4-24.7° (ethanol) (13). Mild acid hydrolysis 

 products include: (a) kromycin ("methynolide" 

 of methymycin) , C17H0SO4 , a biologically inactive, 

 tasteless product. On oxidation with KMn04 in 

 acetone, kromycin yields the lactone of j3-hydro.xy- 

 a-a', 7-trimethylpimelic acid. This lactone is also 

 formed from methymycin and narbomycin; (b) 

 picrocin (desosamine). Hydrochloride: Colorless, 

 water-insoluble needles; m.p. 189-191 °C (decom- 

 position). [a]f = +49.5° (water). CsHi-0.,N- 

 HCl (9,15). Complete structure of picromycin 

 (15, 17) given in Chapter 6. 



Biological activity: Active on gram-positive 

 bacteria, l)ut not on gram-negative bacteria ex- 

 cept certain strains of Xeisseria and Pasteurella. 

 Active on mycobacteria. No activity on filamen- 

 tous fungi or yeasts (5, 7). Reputed to be active on 

 gram-positive bacteria in vivo (16), but has no 

 activity on coccal or Miyagawanella broncho- 

 pneumoniae infections in mice (7). 



Toxicity: MLD (mice) 0.1 to 0.7 gm per kg intra- 

 venously (8). Maximal tolerated dose (mice) 100 

 mg per kg per day subcutaneously, and 250 mg per 

 kg per day intraperitoneally (7). 



Utilization: Favorable effect on bacterial skin 

 infections (3). 



References: 



1. Brockmann, H. and Henkel, W. Naturwiss- 



enchaften 37: 138-139, 1950. 



2. Brockmann, H. and Henkel, W. Chem. Ber. 



84:284-288, 1951. 



3. Suhren, O. Med. klin. (Munich) 46: 722, 



1951. 



4. Lindenbein, W. Arch. Mikrobiol. IT: 361- 



383, 1952. 



5. Brockmann, H. et al. Chem Ber. 8.5: 



426-433, 1952. 



6. Brockmann, H. and Strufe, R. Chem Ber. 



86: 876-884, 1953. 



7. Brodersen,R. et al. Acta Pharmacol. Toxi- 



col. 9:255-258,1953. 



8. Brockmann, H. and Bohne, A. U. S. Patent 



2,693,433, November 2, 1954. 



9. Brockmann, H. et al . Chem. Ber. 87: 856- 



865, 1954. 



10. Brockmann, H. and Oster, R. Naturwiss- 



enschaften 42:155,1955. 



11. Hata, T. et al. J. Antibiotics (Japan) 8A: 



9-14, 1955. 



12. Shibata, M. et al. Quoted in reference 11. 



13. DeSomer, P. Giorn. microl)iol. 2: 216-232, 



1956. 



14. Anliker, R. et al. Helv. Chim. Acta 39: 



1785-1790, 1956. 



