350 



DESCRIPTIONS OF ANTIBIOTICS 



glacial acetic acid and evaporated in vacuo to re- 

 move all methylene chloride. Residual solution 

 extracted with distilled water. Water treated with 

 pH 4.1 acetate butter and e.xtracted with methyl- 

 ene chloride. Extract evaporated to dryness iti 

 vacuo. Tritiu-ated in ether. Separation of com- 

 ponents quinocycline A and B and isoquinocycline 

 B by countercurrent distribution (acetate buffer, 

 pH 4.1, and methylene chloride-CClj , 1:1). 

 Quinocycline B acetate is treated with HCl in 

 ether, and chilled by evaporation to give (juino- 

 cycline B-HCl (1). 



Chemical and physical ■properties: Coiitplex: 

 Brilliant yellow solid. Contains four biologically 

 active components which show the following Rf 

 values on paper chromatography (chloroform- 

 ethyl acetate-formamide) : 0.15 (quinocycline A), 

 0.25 (isoquinocycline A), 0.35 (quinocycline B), 

 0.40 (isoquinocycline B). The complex and all 

 components have ultraviolet absorption spectrum 

 maxima at 228, 258, and 425 m/x. iVIethanolic 0.01 

 A^ HCl solutions are bright yellow; methanolic 

 0.01 A^ NaOH solutions are red. Concentrated 

 H2SO4 solutions are deep red, turning purple on 

 standing. Quinocycline A: [oc]^^ = +159° (meth- 

 anol). Aqueous solution at pH 7.0 is red, stays 

 red on dilution. HCl salt: C = 60.46%; H = 5.8%; 

 N = 4.13%; CI = 5.37%. Quinocycline B: H^^ = 

 + 140° (methanol). Aciueous solution at pH 7.0 is 

 red, turns orange on dilution. C = 60.5%; H = 

 5.8%; N = 3.9%; CI = 4.9%. Isoquinocycline A: 

 [«]hb = +37° (methanol). Aqueous solution at pH 

 7.0 forms yellow precipitate, soluble on dilution. 

 C = 60.81%; H = 5.86%; N = 3.86%; CI = 4.84%. 

 Isoquinocycline B: [aYu^ = +24° (methanol). 

 Aqueous solution at pH 7.0 same as A. C = 60.71% ; 

 H = 5.72%; N = 3.71%; CI = 4.84%. Degradation 

 products: Acid degradations of ciuinocyclines A 

 and B give the same colored product, quinocycline, 

 and dissimilar colorless substances, compound A 

 and compound B, respectively. On acid degrada- 

 tion, isoquinocyclines A and B give a common 

 product, isoquinocycline (the isomer of the acid 

 degradation product, quinocycline) and the same 

 two dissimilar products, compound A and com- 

 povmd B. Quinocycline: HCl: Bright orange 

 needles. [aJng = +244° (methanol). Aqueous solu- 

 tion adjusted to pH 7.0 is a red gel, unchanged 

 by dilution. Rf = 0.10 (same system given under 

 "Complex"). Amphoteric substance. Same ultra- 

 violet absorption spectnun as comi)lex. C = 

 62.15%; H = 4.37%; N = 5.74%; CI = 7.01%. 

 Isoquinocycline: HCl: Reddish orange prisms. 

 [a]pg = +29° (methanol). Acjueous solution ad- 

 justed to pH 7.0 gives an orange-yellow precipi- 



tate, partially dissolved l)y dilution. Rf = 0.20 

 (same system as above). Amphoteric substance. 

 Same ultraviolet absorption spectrum as complex. 

 C = 62.10%; H = 4.29%; N = 5.61%; CI = 6.98%. 

 Compound A: Colorless neutral crystals; m.p. 

 151-152°C. No characteristic ultraviolet absorp- 

 tion spectrum. Negative FeClj , Tolleu, Fehling, 

 and 2,4-dinitrophenylhydrazine tests. C8H14O4 . 

 Highly water-soluble. [a\^ = —111° (water). 

 Coinpound B: Colorless neiitral oil. Positive 

 Fehling, Tollen, and 2,4-dinitrophenylhydrazine 

 tests. Negative FeCU test. Melting point of the 

 hydrazine, 99-100°C. No characteristic ultraviolet 

 a!)sorption spectrum (1). 



Biological activity: Complex: Active on gram- 

 positive bacteria (0.78 to 12.5 //g per ml), including 

 mycobacteria (0.019 to 1.56 ;ug per ml). Not active 

 on gram-negative bacteria or (\ albicans. Active 

 in only a small range on tuberculosis in mice. 

 Quinocycline A and B: Comparable to complex in 

 activity on gram-positive organisms. Up to 10 

 times more active on mycobacteria. Quinocycline 

 B is the more active. Active in a small range on 

 tuberculosis in mice. Quinocycline (degradation 

 product): Comparable to complex. Active in a 

 small range on tuberculosis in mice. Isoquinocy- 

 cline (degradation product): Less active on gram- 

 positive bacteria and nonpathogenic mycobacteria, 

 but comparable to complex against pathogenic 

 mycobacteria (2). Isoquinocyclines A and B: Re- 

 putedly less active than their isomers (1). 



Toxicity: Complex: Mice tolerate 25 mg per kg 

 subcutaneously, with no toxic reactions, and 200 

 mg per kg orally. Quinocycline: Mice tolerate 12.5 

 mg per kg sul)cutaneously, with no toxic reactions, 

 and 50 mg per kg orally. Quinocycline A and B: 

 A is tolerated by mice at 6.25 mg per kg subcu- 

 taneously, and 200 mg per kg orally. B is more 

 toxic (2). 



Ite_ferences: 



1. Celmer, W. D. et al. Antibiotics Ann. 484- 



492, 1957-1958. 



2. McBride, T. J. and English, A. R. Anti- 



biotics Ann. 493-501, 1957-1958. 



Kacenioin> ciiis 



Pri'duced by: Streptomyccs racemochromoyeniis 

 (3). 



Synonym: The original antibiotic 229 may 

 resemble streptothricin III. Racemomycin B 

 belongs to the streptothricin-geomycin group. 



Remarks: This culture was originally (1, 2) re- 

 ported to produce a basic, water-soluble substance 

 termed 229. Later (3) it was found that another 

 substance, 229B, was being formed instead of 229. 



