DESCRIPTIONS OF ANTIBIOTICS 



221 



Reference: 1. Takeuchi, S. et al. J. Antibiotics 

 (Japan) IIA: 1-5, 1958. 



Blaslmj ciii 



Produced by: Streptomijces blastmycelicns (1), and 

 other Streptoinyces spp. (5). 



Synonyms: May be an isomer of antimycin in 

 A3 (5); may contain A3 itself as the major compo- 

 nent, with traces of A4 (-i). 



Method of extraction: Filtered brotli extracted 

 with l)enzene. Mj'celium extracted with 80 per 

 cent aciueous acetone; acetone then evaporated. 

 Re.sidue extracted with benzene, and this benzene- 

 extract combined with the l^enzene from the broth. 

 After washing with phosphate buffer at pH 2.0 

 and evaporation in vacuo, an oily syrup is ol)- 

 tained. Syrup extracted with petroleum ether in a 

 Soxhlet apparatus. Precipitated from the petro- 

 leum ether solution. Recrystallized from benzene- 

 petroleum ether or ether-petroleum ether (1). 



Chemical and physical properties: White needles; 

 m.p. 1(J7°C (1) or 168-169°C (3). Very soluble in 

 acetone, ethyl acetate, benzene, chloroform, 

 methyl isol)utyl ketone, and carbon tetrachloride; 

 soluble in methanol, ethanol, and ether; .slightly 

 soluble in n-hexane and cyclohexane; scarcely 

 soluble or insoluble in petroleum ether and water. 

 Ultraviolet absorption maxima at 225 irxfx (^icm 

 ()25) and 321 m^u (E'lcm 116). Bathochromic shift 

 on addition of base, to 222 and 245 m^. Infrared 

 absorption spectrum given in reference 1. [a]^ = 

 +77.4° (c = 1 per cent in methanol). Positive 

 FeCls , diazo, hydroxamic acid, and biuret tests; 

 negative ninhydrin, Molisch, Fehling, Tollen, 

 Ehrlich, and Millon tests. C = 59.81'^.; H = 

 6.89%; N = 5.34S^b- No S, P, halogen, or ash. 

 C-.eHseN-jOg . Acetylation gives a l)iologically in- 

 active diacetyl derivative; white fibrous crystals; 

 m.p. 146-150°C. Mild alkaline hydrolysis gives 

 l)roducts including a neutral oil (blastmycinone), 

 b.p. 190-191 °C, and an acidic substance (blast- 

 mycic acid) (I), m.p. 141.5-142°C. Further alkaline 

 hydrolysis of I gives formic acid and antimycic 

 acid (structure: N-(3-aminosalicyloyl)-L-threo- 

 nine), which is also a degradation product of the 

 antimycins. Complete structure of blastmycin 

 (1, 3) is given in Chapter 6. 



Biological activity: Active on certain finigi, in- 

 cluding Piricularia oryzae and P. grisea at 0.005 

 mg per ml. Also active on Gloeosporium lacticola, 

 Corticium centrifugus, Ophiostoma Jimbriata, Scle- 

 rotinia hydrophilum, but not aspergilli, penicillia, 

 fusaria, Elsinoe, or C. albicans (1). Not active on 

 bacteria. Inhibits anaerobic glycolysis of Ehrlich 



ascites tumor cells. Blocks electron transport be- 

 tween cytochromes B and C (2). 



Toxicity: LD50 (mice) 1.8 mg per kg intraperi- 

 toneally (1). 



References: 



1. Watanabe, K. ct al . J. Antil)iotics (Japan) 



lOA: 39-45, 1957. 



2. Lardy, H. A. et al. Arch. Biochem. Biophys. 



78:' 587-597, 1958. 



3. Yonehara, H. and Takeuchi, S. J.Anti- 



l)iotics (Japan) llA: 254-263, 1958. 



4. Liu, W. C. Thesis, University of Wisconsin, 



1958. 



5. Karasawa, K. et al. J. Gen. Appl. Micro- 



biol. .1: 13-20, 1959. 



B< 



-lidi 



Produced by: Streptomyces rochei and an uniden- 

 tified Streptoinyces sp. (1, 3). 



Method of extraction: Broth-filtrate extracted 

 with butyl acetate at pH 7. Extract evaporated 

 to dryness. Residue purified by treatment with 

 bentonite clay in butyl acetate, then by extraction 

 into alkali from ether. Alkaline extract acidified 

 and extracted with benzene. Benzene concentrated 

 to precipitate the antibiotic. Recrystallized from 

 benzene. Can also be adsorbed onto bentonite clay 

 from benzene and eluted with methanol (1, 4). 



Chemical and physical properties: Acidic sub- 

 stance; m.p. 145-146°C. Molecule may contain a 

 .site of conjugated unsaturation. Soluble in eth- 

 anol, isopropyl alcohol, and benzene, [a]'^ = —28° 

 (ethanol). Ultraviolet absorption spectrum maxi- 

 mum at 256 m/j. (£^i'Jn, 550) (isopropyl alcohol). 

 CosHjsOeN. Forms a crystalline methyl ester (m.p. 

 153-154°C) and a crystalline p-nitrobenzyl ester 

 (m.p. l(;i°C) (1, 4). 



Biological activity: Active in vitro and in vivo 

 (mice) on Borrelia. Active in vitro on certain 

 micrococci and Sarcina lutea, but not active on 

 Staph, aureus, E. coli, or B. subtilis. Active on 

 Tetrahyniena geleii. Not active in vivo on other 

 bacterial, viral, or Treponema pallidum infections 

 in mice (1-4). Slightly active on carcinoma 1025 

 and grand epidermoid carcinoma (mice) (6). 



Toxicity: LD.50 (mice) 74.7 mg per kg subcutane- 

 ously, 39.0 mg per kg intravenously. LD.5n (rat) 

 1.78 mg per kg subcutaneously (2). Poor growth 

 in rats fed borrelidin is partially overcome Ijy 

 addition of niacin or trj^ptophan to diet (5). 



References: 



1. Berger, J. et al. Arch Biochem. 22: 476- 



478, 1949. 



2. Buck, M. et al. Trans. N. Y. Acad. Sci. 11: 



207-210, 1948-1949. 



