DESCRIPTIONS OF ANTIBIOTICS 



397 



nously; 10 mg per kg produces delayed death with 

 abnormality of the liver. Toxicity decreased by 

 simultaneous administration of DL-methionine 

 or glucuronic acid (2). LD50 (mice) 10 to 20 mg 

 per kg subcutaneously (3). 

 References: 



1. Katagiri, K. et al. Report 85th Meeting 



Japan Antibiotic Research Assoc, 1954, 

 as given in reference 2. 



2. Kikuchi, K. J. Antibiotics (Japan) 8A: 



145-147, 1955. 



3. Nishimura, H. et al. J. Antibiotics (Japan) 



9A: 60-62, 1956. 



4. Yamamoto, H. et al. Ann. Rept. Takeda 



Research Lab. 16: 28-31, 1957. 



5. Miyakawa, T. et al. Japan. J. Microbiol. 



2: 53-62, 1958. 



6. Ohkuma, K. J. Antibiotics (Japan) ISA: 



361, 1960. 



Trehalcsaniine 



Produced by: Streptomyces sp. resembling S. 

 lavendulae (1). 



Method of extraction: Active fraction adsorbed 

 from broth-filtrate by activated carbon; eluted 

 with water at pH 2.5. Readsorbed on IR-120 and 

 eluted with ammonium hydroxide. Eluate con- 

 centrated in vacuo, adjusted to pH 5, diluted with 

 methanol, and precipitated with acetone. Purifi- 

 cation by chromatography on AI2O3 and elution 

 with 70 per cent aqueous methanol. Recrystallized 

 from anhydrous methanol (1, 2). 



Chemical and physical properties: Amino disac- 

 charide. HCl: White crystalline powder, [ajo = 

 -fl76° (c = 2.4 per cent in water). Basic group: 

 pKb = 6.9. Ci2H230ioN-HCl. Positive ninhydrin 

 test. Negative Fehling, Benedict, and ammoniacal 

 silver nitrate tests. Infrared spectrum given in 

 reference 2. No ultraviolet absorption. Stable to 

 dilute acid and alkali under mild conditions. 

 Ammonia is liberated by boiling with strong al- 

 kali. Octaacetyl monohydrate derivative: m.p. 99- 

 102°C. Ultraviolet absorption spectrum maximum 

 of the acid degration product at 284 nxfi. Trehalos- 

 amine is a-D-glucopyranosido-2-desoxy-2-amino- 

 a-D-glucopyranoside (1, 2): 



H 



Biological activity: Very slightly active on gram- 

 positive bacteria, including mycobacteria, and 

 certain gram-negative bacteria (E. coli but not 

 Klebsiella friedlanderi) and yeasts. Not active on 

 Endamoeba histolytica (1). Antimycobacterial 

 activity antagonized by valicin, esculin, and 

 trehalose. Action of trehalose is competitive in 

 certain cases (3). 



Toxicity: LD50 (mice) 5.4 gm per kg (1). 



References: 



1. Arcamone, F. et al. Giorn. microbiol. 2: 



205-214, 1956. 



2. Arcamone, F. and Bizioli, F. Gazz. chim. 



ital. 87:896-902,1957. 



3. Ghione, M. and San Filippo, A. Cuorn. 



microbiol. 3: 189-196, 1957. 



Trichoinycin 



Produced by: Streptomyces hachijoensis strains, 

 resembling S. rubrireticuli (1, 5, 7); Streptomyces 

 sp. (10). 



Synonym: Belongs to the same group as candi- 

 cidin and ascosin. 



Method of extraction: 1. Extracted from myce- 

 lium with warm acetone, methanol, or ethanol. 

 Best method: 80 per cent acetone at pH 7.4 to 

 8.0. Extract concentrated in vacuo, and aqueous 

 residue adjusted to pH 5.4 to precipitate yellow 

 trichomycin. Purified by countercurrent distribu- 

 tion (chloroform-methanol-pH 8.5 Sorensen's 

 buffer, 1:1:0.5). Active fractions concentrated in 

 vacuo and adjusted to pH 5.4. II. Extracted from 

 culture-filtrate by adsorption on 1 per cent Japa- 

 nese acidic clay and elution with butanol-metha- 

 nol-water (4:1:1). Eluates concentrated in vacuo 

 and dried (2). III. Acetone-extracts of mycelium 

 purified by chromatography on alumina (devel- 

 oper: pyridine-butanol-water, 3:4:7); 20 per cent 

 ammonium sulfate added to active fractions. 

 Benzene added to upper layer. Lower layer freeze 

 dried to yield trichomycin (14). Precipitated from 

 warm pyridine-dioxane-water-butyl acetate (30: 

 40:52:18) on chilling. Precipitated from cold 

 alkaline water with acetone (17). Chromato- 

 graphed on alumina from water (pH 8.5 to 9.0) to 

 give three fractions, A, B, and C. Development 



/C- 



OH 



I 

 C 



H 



CH2OH 



H 



I 

 ^C 



OH 



NH2/ 



Y 



H 



H 



OH 



/C— 

 H 



H 



I 



■?\ 



OH 

 H 



I 

 CH2OH 



OH 



C 



H 



