300 



DESCRIPTIONS OF ANTIBIOTICS 



maxiimun at 230 m^ in methanol. Tentative 

 empirical formula: CeoHinOaiNs . Yellow color, 

 turning brown with sulfuric acid. Brown, non- 

 specific Molisch test. Negative Fehling, FeCls, 

 and ninhydrin tests. Strong acid hj'drolysis yields 

 three ninhydrin-positive fragments. Infrared ab- 

 sorption spectrum given in reference 1. 



Biological activity: Active against gram-i)ositive 

 bacteria and fungi. 



Toxicity: LDso (mice) 15 mg per kg intraperi- 

 toneally, 350 mg per kg orally. 



Reference: 1. Arcamone, F. M. et al. Giorn. 

 niicrol)iol. 7: 207-216, 1959. 



Meseiileriii 



Produced by: Nocardia iiiesentericd . 



Method of extraction: Extraction of broth at pH 

 7.4 with butyl acetate. Concentration to small 

 volume under vacuum. Concentrate cooled; crude 

 crystals of azomycin precipitate and are removed. 

 The concentrate then extracted with water at pH 

 2.0. Aqueous layer adjusted to pH 8.0 and ex- 

 tracted with benzene. Evaporation of the benzene 

 leaves a crude white amorphous powder, which is 

 dissolved in methanol and treated with active 

 carbon. Filtrate evaporated to dryness and the 

 residue dissolved in benzene. Benzene solution 

 chromatographed over a column of alumina. Elu- 

 tion with benzene yields antil)iotic 440; further 

 elution with benzene and acetone yields mesen- 

 terin. 



Chemical and physical properties: Basic, color- 

 less substance. Crystallized as needles; m.p. 122- 

 126°C. Strong end-absorption of ultraviolet light 

 in ethanolic solutions. C = 65.82%; H = 7.10%; 

 X = 8.66 to 8.44%. No halogen or S. Negative 

 ninhydrin, Millon, biuret, Tollen, Fehling, and 

 FeCl.i tests. Positive Molisch reaction. Very 

 soluble in methanol, ethanol, ethyl acetate, butyl 

 acetate, and ether. Soluble in benzene and acidic 

 water. Slightly soluble in water. Insoluble in 

 petroleum ether. A 10 per cent loss of activity at 

 pH 6.0 upon heating for 30 minutes at 100°C in 

 atjueous solution. 



Biological activity: Active in vitro against gram- 

 positive bacteria, including mycobacteria. No 

 activity against gram-negative bacteria. 



Toxicity: LD50 >100 mg per kg. (Route of in- 

 jection and animal used not reported.) 



Reference: 1. Ueda, M. and ITmezawa, H. J. 

 Antibiotics (Japan) 8A: 1(;4-1()7, 1955. 



Melhyniycin 



Produced by: Streptoniyces sp. (1) and S. euro- 

 cidicus (10). 



Synonym: Antibiotic 11 B (10). 



Remarks: Belongs to the erythromycin-carbo- 

 mycin-proactinomycin group. Differs from picro- 

 mycin only in point of attachment of desosamine 

 to the lactone ring. 



Method of extraction: Broth-filtrate extracted 

 with amyl acetate at pH 9.5. Back-extracted into 

 dilute sulfuric acid. Acid washed with chloroform 

 at pH 2.5, then extracted with it at pH 9.5. Con- 

 centration of extract and dilution of concentrate 

 with Skellysolve C gives needles of methymycin. 

 Recrystallized from absolute ethanol (1). Purified 

 by chromatography. Crystallized from ethyl 

 acetate (5). 



Chetnicdl and physical properties: Macrolide (9). 

 Needles, m.p. 203-205°C (from ethyl acetate) ; or a 

 polymorphic modification (prisms from ethanol), 

 m.p. 195.5-197°C (5). Free base: Soluble in meth- 

 anol, acetone, chloroform, and dilute acids; 

 moderately solul)le in ethanol and ether; insoluble 

 in water and hexane. Ultraviolet absorption spec- 

 trum maxima at 223 to 225 m^t (e = 10,500) and at 

 322 mix (e = 47) (ethanol) (1, 5). Infrared spec- 

 trum given in reference 1. [a]~n = +61° (c = 0.7 

 per cent in methanol). Positive permanganate and 

 Br tests. Negative Molisch, biuret, ninhydrin, and 

 FeCls tests. pKi, = 5.7 (1,6). Rf values in various 

 systems (paper chromatography) given in refer- 

 ence 3. Sulfate: needles; m.p. 173-178°C. Soluble in 

 methanol and water (1). 2 ,^-Dinitrophenylhydra- 

 zone: Orange nee(\\eii;Vi\.\). 205-207°C (5). Quater- 

 nary salt with methyl iodide: C26H46NO7I; m.p. 

 190°C. [al, = +31.0° (ethanol) (7). Mild acid 

 hydrolysis products include desosamine (6), also 

 foimd in erythromycin. Oxidation with KMn04 in 

 acetone yields the lactone of ^S-hydroxy -«,«', 7- 

 trimethylpimelic acid. Both products are also 

 produced from narbomycin and picromycin (8). 

 Formula of methymycin: C25H43NO7 . C = 63.93%; 

 H = 9.28%; N = 2.84%; 2N— CH3 = 5.83%; 6C— 

 CH3 = 18.3% (5). Complete structure (6) given in 

 Chapter 6. 



Biological activity: Active against certain strains 

 ot gram-i)ositive bacteria and a few strains of 

 gram-negative bacteria {Malleomyces mallei, Br. 

 suis, and Pasteurella tularensis). No antifungal 

 activity (1). Not active on Toxoplasma gondii 

 infections in mice (4). 



Utilization : Suppressive but not curative effect 

 on clinical brucellosis (2). 



References: 



1. Donin, M. N. e^ a?. Antibiotics Ann. 179- 



185, 1953-1954. 



2. Max, G. C. and Mendez, D. Antibiotics & 



Chemotherapy 4: 83-86, 1954. 



