THE CHEMISTRY AND MANUFACTURE OF ANTIBIOTIC SUBSTANCES' NATHAN H. HAMILTON Squibb Institute for Medical Research New Brunswick, New Jersey
NATURE AND SOURCES OF ANTIBIOTICS
F~~the benefit of the or the teacher who has found it difficult to keep abreast of the tremendous advances in the field of antibiotics, it is felt that a review of the chemistry, manufacturing techniques, and recentdevelopments in this field will he of particular interest at the presenttime, order t,o complete a broad presentation of this nature, the specific therapeutic effectsof the mostimportant antibiotics and the commercial significance of these mat,erialswill also be considered. ~h~~~have been various interpretations of the meaning of the term "antibiotic," but Waksman ( 1 ) has recently given us an excellent working definition. He has said that an antibiotic is a substance produced by microorganisms, which has the capacity of inhibiting the growth and even of destroying other microorganisms. Essentially the same concept has been stated somewhat differently by Benedict and Langlykke (Z), who have chosen to define an antibiotic as "a chemical compound derived from or produced by living organisms, which is capable, in small concentration, of inhibiting the life processes of microorganisms." Of the six major groups of microorganisms, including bacteria, actinomycetes, molds, yeasts, protozoa, and viruses, only the first three have been found to produce antibiotics of value in the treatment of disease. Bacitracin and tyrothricin are probably the most wellknown antibiotics of bacterial origin, while streptomycin and penicillin are unquestionably the most widely used antibiotics of actinomycete and mold origin, respectively. In addition, two new antibiotics derived from actinomycetes, aureomycin and chloromycetin, are becoming increasingly important, especially in the treat'Presented a t the Eleventh Summer Conference of the New England ilnsocirution of Chemistry Teachem, univemity d IIampshire, Durham, New Hampahire, August 23, 1949.
ment of diseases caused by rickettsiae and some of the larger so-called viruses. Neomycin, a new antibiotic derived from an actinomycete, may also prove to be of considerable value in treating cases of streptomycinresistant There appears to be a complete lack of similarity in the molecular structures of the various antibiotics. Likewise, the chemical properties of these materials lndlcate that they are of diverse nature, including ~ 0 1 ~ pe~tides, sulfur-containing compounds, lipids, pigments, quinones, complex polysaccharides, and organic bases. The structural formulas of penicillin and s t r e p t O m ~ c i nare shown S
0
'CH-CH-NHL Hood \0 Penicillin (Beta-Lactarn Atructure)
Variations in the "R" group in the structure for penicillin are responsible for the existence of several types of this antibiotic. Of these types, ~enicillinG is the one of choice in practically all cases. These natural penicillins so far identified are listed below (9): TYPE G F Dihydro F X K
R -CX-C,H, -CH?-CH=CH-CHpCH1 -
