S Umezawa

Institute of Bio-organic Chemistry, Ida, Nakahara-ku, Kawasaki-shi, 211 Japan The first aminoglycoside antibiotic described was streptomycin discovered by Waksman and coworkers in 1944, and, since then, remarkable development has been made in this field of antibiotics. The number of structurally elucidated aminocyclitol antibiotics of microbial origin is now about one hundred. Various antibiotics among them have been utilized for chemotherapy, being especially useful for treatment of serious...

The Structures of New Fortimicins Having Double Bonds in Their Purpurosamine Moieties

KUNIKATSU SHIRAHATA, GEN SHIMURA, SEIGO TAKASAWA, TAKAO IIDA, and KEIICHI TAKAHASHI Tokyo Research Laboratory, Kyowa Hakko Kogyo Co. Ltd., 3-6-6 Asahimachi, Machida, Tokyo 194, Japan In 1972, Dr. Nara and his co-workers of Kyowa Hakko discovered a new type of aminoglycosides, named fortimicins (1,2), in the fermentation broths of Mioromonospora species. Fortimicin is a pseudo disaccharide composed of a 6-epi-purpurosamine B and a novel 1,4-diaminocyclitol. Fortimicin A(FM-A) is the major...

Multiple Interactions of Aminoglycoside Antibiotics with Ribosomes

Bacterial Physiology Unit, Harvard Medical School, Boston, MA 02115 Streptomycin (Str) has been studied longer than any other antiribosomal antibiotic, yet until relatively recently the mechanism of its bactericidal action has been quite unclear. One reason is that this antibiotic exerts an unusually wide variety of effects, some of which are mutually exclusive. In addition, for many years protein synthesis could be analyzed in vitro only with synthetic polynucleotide messengers, which bypass...

Biosynthesis and Mutasynthesis of Aminocyclitol Antibiotics

Roger Adams Laboratory, University of Illinois, Urbana, IL 61801 Aminocyclitol antibiotics constitute a large and diverse group of important, clinically useful compounds. As is appropriate to a class of unusual structure and important activity, considerable attention has been directed toward detecting and understanding the reactions involved in the synthesis of these antibiotics by the microorganisms which produce them. In the ensuing discussion, special attention will be directed toward the...

The Effect of OMethylation on the Activity of Aminoglycosides

DeVAULT, A. C. SINCLAIR, R. S. EGAN, M. CIROVIC, R. STANASZEK, and S. MUELLER Abbott Laboratories, Division of Antibiotics and Natural Products, North Chicago, IL 60064 Following the discovery by Hamao Umezawa (_1) and co-workers that certain aminoglycoside resistant organisms of clinical origin owed their resistance to an R-factor mediated ability to phosphorylate kanamycin and neomycin at the 3f-hydroxyl group chemical modification of these antibiotics was...

Hn xV0H

M e 217(C9HiyN204) m e 189 (CgH- N ) Scheme 1. Mass fragmentations of FM-KF and KG purpurosamine moiety is 14 atomic mass units less than those of the corresponding peaks of FM-KG. The purpurosamine moiety of FM-KF is thus 4,5-dehydropurpurosamine-C, which is known to be a component of sisomicin (8., _9) . The 13-C NMR (CMR) of FM-KG free base exhibited all the fifteen carbons1 signals. When the CMR were taken at various pDs, the resonance of each carbon, depending on its environment, gave...

The Structures of Diastereomers of Dihydrospectinomycins

Hoffmann-La Roche Inc., Chemical Research Department, Nutley, NJ 07110 Spectinomycin (1) (1,2) as well as the dihydrospectinomycins 2 and 2, (.3)(Figure 1) represent unusual structures among the aminocyclitol antibiotics. Most antibiotics of this class contain streptamine or 2-deoxystreptamine linked to at least one a-pyranose unit. Spectinomycin, however, contains 2-epi-N,N'-dimethylstreptamine linked to a single sugar unit by a 3-glycosidic bond. Another interesting feature of structures 1,...

Tetsuo Suami

Department of Applied Chemistry, Faculty of Engineering, Keio University, Hiyoshi, Yokohama 223, Japan Chemical and biological modifications of aminocyclitol antibiotics have been extensively studied to elucidate a structure-antimicrobial activity relationship. Most of the works done so far concerns modifications of an amino sugar moiety of an antibiotic. Before 1969, few studies had been done on the dependence of antimicrobial activity on an aminocyclitol moiety structure. In 1969, Rinehart...

The Structures of Minor Components of the Fortimicin Complex

STANASZEK, M. CIROVIC, S. L. MUELLER, R. E. CARNEY, P. COLLUM, E. E. FAGER, A. W. GOLDSTEIN, D. J. GRAMPOVNIK, P. KURATH, J. R. MARTIN, G. G. POST, J. H. SEELY, and J. TADANIER Abbott Laboratories, Division of Antibiotics and Natural Products, North Chicago, IL 60064 The fortimicins are a new group of potent aminoglycoside antibiotics discovered under a joint research agreement between the Kyowa Hakko Kogyo Company and Abbott Laboratories. They are produced by...

Spectinomycin Modification

CARNEY Abbott Laboratories, Division of Antibiotics and Natural Products, North Chicago, IL 60064 Spectinomycin is an aminocyclitol antibiotic unique both in structure 1 2 and in biological activity. The antibiotic Figure 1 is a pseudodisaccharide in which a non-aminosugar moiety, actinospectose, is fused to an aminocyclitol, actinamine or N,Nf-dimethy1-2-epi-streptamine by both a 3-glycosidic bond and a hemiketal linkage. The bioactivity of spectinomycin...