58 



NATURE, FORMATION, AND ACTIVrriES 



H ijdro.ri/streptomijci)! , which is pi'ochicod 

 by certain Streptomijccs, cHft'ers from strepto- 

 mycin in that it has a hych'oxymethyl group 

 instead of a methyl group in the streptose 

 moietv: 



CHO 



CH3 



OH' 



Streptomycin 



CH,OH 



CHO 



OH 



Hydroxystrcptomycin 



This antibiotic seems to offer nf) advantage 

 over streptomycin. 



Pseudostreptomycin is composed of two 

 molecules of streptomycin linked together 

 through their aldehyde groups by condensa- 

 tion with ammonia. The formula is thus: 



,S.l/— CHOH— XH— CHOH—SAI 



where Si\I stands for streptomycin minus 

 the — CHO group. Pseudostreptomycin has 

 little biological activity and is very toxic. 

 It is converted to streptomycin in acjueous 

 acidic sohition. 



neomycins B and C were later isolated. An 

 antibiotically active degradation product, 

 neomycin A or neamine, produced in the 

 culture or by chemical hydrolysis, w^as also 

 obtained. The ninhydrin and other color 

 tests, as well as specific test bacteria, can 

 be utilized for the separation of the various 

 neomycins. 



Neomycin B is composed of fovn- cyclic 

 moieties, three of which have a carbon 

 skeleton composed of six carbons and one of 

 five carbons. One diaminohexose moiety is 

 linked to the pentose, D-ribose, to form a 

 Cii fragment called neobiosamine, and an- 

 other molecule of a diaminohexose is linked 

 to a diaminotrihydroxycyclohexane (2- 

 desoxystreptamine) to form a C12 moiety 

 called neamine. Neamine has some antibiotic 

 activity of its own. Neobiosamine and ne- 

 amine are linked together to form the C23 

 molecule of neomycin B, which has thus a 

 total of six amino groups. Neomycin C is an 

 isomer of neomycin B which is somewhat 

 less active biologicallv. The difference be- 



XH, 



C,H,O3(NH0a— 1-0 



I 

 Diaminohexose ! 



OH OH 

 d-Ribose 



I I 

 I I 

 I I 



"C«H802(XH2)2 



Diaminohexose 



— O 



NH2 



Neobiosamine 



Neomvcins 



The neomycins are very similar to the 

 streptomycins, but they do not contain 

 guanido groups. They are formed of cyclic 

 aminated moieties. These basic, stable, 

 water-soluble substances are active against 

 gram-positive and gram-negative bacteria 

 and often have antiprotozoal activity. 



Neomycin was first isolated in 1948 by 

 Waksman and Lechevalier from a culture of 

 ;S. fradiae. It w-as soon recognized that this 

 antibiotic was made up of se\'eral chemical 

 entities, the mixture being designated as the 

 "neomycin complex." From this mixture, 



OH OH 

 2-Desoxystreptamine 

 Neamine 



tween the two isomers is in the diamino 

 hexose which is part of neobiosamine. 



Kanamycin A is formed of three aminated 

 cyclic moieties. These are 2-desoxystrept- 

 amine, which is also found in neomycin, and 

 two aminohexoses: 



NH. 



OH 

 OHCH,,- 



NH.CH.- 

 OH- 



-OH 



-O^ 



OH- 



.0 . 



OH 



-OH 



NH.. 



NH2 



