DESCKll'l IONS OF ANTIBIOTICS 



355 



loiver ak'ohols, chloroforin, ether, and acetone. 

 At other pH values, soluble in water, lower alco- 

 hols, and glacial acetic acid. Orange-red at acid 

 pH, purple-red at neutrality, and blue at alkaline 

 pH. Light-absorption maxima at 504, 535, 542, and 

 575 niju (benzene) or 567 and 536 m^ (methanol) 

 (1, 4). Irreversibly destroyed in strong Ijase or 

 acid (4). Pirrate: Yellow-red substance. Soluble 

 in acetone and hot ethanol. Insoluble in water, 

 ether, and benzene. Hydrochloride and phosphate 

 are water-soluble (1, 4). Pcrchlorate: Crystalline 

 substance; m.p. 198°C (decomposition, uncor- 

 rected). Soluble in alcohol, acetone, and pyridine. 

 Sparingly soluble in water. In acetic anhydride, 

 gives a yellow-red solution turning l)luish violet 

 with red fluorescence ui)on addition of pyroboric 

 acetate (4). Rhodomi/rin A: H j/drodilnriile: Red 

 prism-^; m.p. 205°C. Soluble in water and lower 

 alcohols. Very slightly solul)le in Ix'uzene and 

 chloroform. Insoluble in ether and petroleum 

 ether. [aloge-Teo = +178° ± 10° (c = 0.13 per cent 

 in methanol). Ultraviolet light -absorption spec- 

 trum maxima at about 230, 260, 295, and 500 m^ 

 (methanol). C = 54.55%; H = 6.82%; () = 26.13%; 

 N = 3.20%; CI = 9.64%,. Pcrchlorate: Fine red 

 needles; m.p. 188°C (6). Mild hydrolysis products 

 of rhodomycin A include "rhodosamine," which 

 is isomeric with "picrocin" from picromycin (5): 



OH 



H— C 



CH., 



I 



CH— N(CH;,)2 



CH— OH 



I 

 CH— O 



CH:, 



lihudo.Hiicin B: Hydrochloride: lietl jjrisms; m.p. 

 180°C. Soluljle in lower alcohols. Moderately 

 soluble in water and acetone. Scarcely solul)le in 

 chloroform and benzene. [aJfiOB-ren = -j-174° ±10° 

 (c = 0.05 per cent in methanol). Ultraviolet 

 absorption spectrum maxima at about 230, 230, 

 295, and 500 m^. Cn-wH^.-iTOe-TN -HCl : C = 

 54.88%; H = 6.70%; O = 23.02%; X = 3.41%; 

 CI = 8.94%. Base: Amphoteric substance. Soluble 

 in dilute acid; very scarcely soluble in water (6). 

 Rhodomycinoris :These are the chromophores of the 

 rhodomycins (see "Remarks"). Rf values (ben- 

 zene-formamide) : a, 0.10; p, 0.27; y, 0.64; 5, 0.77; 

 and e, 0.85 (9). fi-Rhodomyrinon (chromophore of 

 rhodomycin A): CsnHie.DjON or CjsHid.iijOu . 



Mild alkaline hydrolysis yields -y-rhodomycinon, 

 C20H16-18O7 or C23H20-22O8 (8). 



Biological activity: Complex: Active on certain 

 gram-positive bacteria, including Staph, aureus 

 at 1:2 X 10^, but not on gram-negative bacteria, 

 except Honophihis and Brucella. Not active on 

 fungi (1). 



References: 



1. Brockmann, H. and Bauer, H. Naturwis- 



senschaften 37:492-493, 1950. 



2. Lindenbein, W. Arch. Mikrobiol. I": 3(>1- 



383, 1952. 



3. Brockmann, H. and Borchers, I. Chem. Ber. 



86: 21)1-269, 1953. 



4. British Patent 708,749, May 12, 1954. 



5. Brockmann, H. and Spohler, E. Natiu'wis- 



senschaften t2: 154-155, 1955. 



6. Brockmann, H. and Patt, P. Chem. Ber. 



88: 1455-1468, 1955. 



7. Brockmann, H. and Franck, B. Chem. Ber. 



88: 1792-1818, 1955. 



8. Brockmann, H. and Boldt, P. Naturwis- 



senschaften 44:616,1957. 



9. Corbaz, R. el al . Arch. Mikrol)i()l. 25: 



325-332, 1957. 



Rifomycins 



Produced hy: Strcptoniyces inediterranei. 



Remarks: Tliis organism produces a mixture of 

 five antibiotics (rifomycins A, B, C, D, and E). 

 Rifomycin B is a stable acidic component; rifo- 

 mycins A, C, D, and E are neutral or slightly 

 acidic unstable substances. 



Method of extraction: Filtration of broth at pH 

 7.0 to 8.0. Extraction of the broth with ethyl 

 acetate at pH 2.0. Back-extraction in pH 6.5 to 

 7.5 buffer. The ethyl acetate layer can be concen- 

 trated //( vacuo, and addition of petroleum ether 

 yields crude rifomycin complex containing Frac- 

 tions A, C, 1), and E. The buffer layer is acidified 

 to pH 2.0 and extracted with ethyl acetate. The 

 solvent is concentrated in vacuo and rifomycin B 

 crystallizes (1). 



Chemical and physical properties: Rifomycin 

 complex: Amorphous brown powder. Soluble in 

 water at pH 9 to 10, giving a dark red solution 

 (maximal solubility, 2 per cent). Soluble in ace- 

 tone, chloroform, ethyl acetate, methanol, and 

 ethanol. Insoluble in i)etroleum ether. Solutions 

 of rifomycin complex at pH 6.0 lose 10 per cent of 

 their activity in 24 hoiu-s at 5°C, and 75 per cent 

 at 37°C. Very \instable at neutral or alkaline pH. 

 Stal)ility can be improved by addition of ascorbic 

 acid; however, ascorbic acid increases the insta- 

 bility in acidic solutions. The complex can be 



