59-01-8

Usage

Uses

Used in Pharmaceutical Industry:
Kanamycin is used as an antibiotic for the treatment of various bacterial infections caused by pathogens such as E. coli, Proteus species (both indole-positive and indole-negative), Enterobacter aerogenes, Klebsiella pneumoniae, Serratia marcescens, and Acinetobacter species. Its bactericidal action is due to its ability to bind to the ribosome and disrupt protein synthesis, ultimately leading to the death of bacterial cells.
Used in Agricultural Industry:
Kanamycin is also used in agriculture as a selective agent in the cultivation of genetically modified organisms (GMOs). It is employed to identify and maintain the presence of specific genetic traits in plants, ensuring the successful integration of desired genes into the plant's genome.

Sources

Pindell, M. H. "The pharmacology of kanamycin--a review and new developments." Annals of the New York Academy of Sciences 132.2(1966): 805–810. https://www.annualreviews.org/doi/pdf/10.1146/annurev.bi.42.070173.002351 Spelman, D. W., M. Mcdonald, and W. J. Spicer. "Aminoglycoside antibiotic agents: a review." Medical Journal of Australia 151.6(1989): 346. https://en.wikipedia.org/wiki/Kanamycin_A https://www.drugbank.ca/drugs/DB01172

Indications

Kanamycin, O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)-O-[6-deoxy- 6-amino-α-D-glucopyranosyl-(1→4)]–2-deoxy-D-streptamine (32.4.6), is isolated from a culture fluid of the actinomycete Streptomyces kanamyceticus, which produces three antibiotics—kanamycins A, B, and C.Kanamycin A is similar to streptomycin and neomycines, and it possesses a broad spectrum of antimicrobial action. It is active with respect to most Gram-positive and Gramnegative microorganisms (staphylococci, colon bacillus, klebisella, Fridlender’s bacillus, proteus, shigella, salmonella).It is used to treat sepsis, meningitis, osteomyelitis, peritonitis, pneumonia, pyelonephritis, pyelocystitis, infected wounds, and post-operational, purulent complications that are caused by microorganisms sensitive to this drug. Kanamycin is used to treat tuberculosis of the lungs and other organs upon resistance to other antituberculosis drugs. Synonyms of this drug are karmycin, kamaxin, resistomycin, and many others.

Antimicrobial activity

It is active against staphylococci, including methicillin-resistant strains. Other aerobic and anaerobic Gram-positive cocci and most Gram-positive rods are resistant, but M. tuberculosis is susceptible. It is widely active against most aerobic Gram-negative rods, except Burkholderia cepacia and Sten. maltophilia. Treponema pallidum, Leptospira and Mycoplasma spp. are all resistant.

Acquired resistance

Resistance is usually plasmid borne and due to enzymatic inactivation of the drug by enzymes that also inactivate gentamicin or tobramycin . Resistance due to reduced permeability is also encountered.

Pharmacokinetics

Cmax 500 mg intramuscular： c.15–20 mg/L after 1 h Plasma half-life: 2.5 h Volume of distribution: 0.3 L/kg Plasma protein binding: Low Absorption and distribution Very little is absorbed from the intestinal tract. The peak plasma concentration in the neonate is dose related: concentrations of 8–30 mg/L (mean 18 mg/L) have been found 1 h after a 10 mg/kg dose. The drug is confined to the extracellular fluid. The concentration in serous fluids is said to equal that in the plasma, but it does not enter the CSF in therapeutically useful concentrations even in the presence of meningeal inflammation. Excretion It is excreted almost entirely by the kidneys, almost exclusively in the glomerular filtrate. Up to 80% of the dose appears unchanged in the urine over the first 24 h, producing concentrations around 100–500 mg/L. It is retained in proportion to reduction in renal function. Less than 1% of the dose appears in the bile. In patients receiving 500 mg intramuscularly preoperatively, concentrations of 2–23 mg/L have been found in bile and 8–14 mg/kg in gallbladder wall.

Clinical Use

Formerly used for severe infection with susceptible organisms, it has largely been superseded by other aminoglycosides.

Side effects

Intramuscular injections are moderately painful, and minor side effects similar to those encountered with streptomycin have been described. Eosinophilia in the absence of other manifestations of allergy occurs in up to 10% of patients. Other manifestations of hypersensitivity are rare. As with other aminoglycosides, the most important toxic effects are on the eighth nerve and much less frequently on the kidney. Renal damage is seen principally in patients with pre-existing renal disease or treated concurrently or sequentially with other potentially nephrotoxic agents. The drug accumulates in the renal cortex, producing cloudy swelling, which may progress to acute necrosis of proximal tubular cells with oliguric renal failure. Less dramatic deterioration of renal function, particularly exaggeration of the potential nephrotoxicity of other drugs or of existing renal disease, is of principal importance because it increases the likelihood of ototoxicity. Vestibular damage is uncommon but may be severe and prolonged. Hearing damage is usually bilateral, and typically affects frequencies above the conversational range. Acute toxicity is most likely in patients in whom the plasma concentration exceeds 30 mg/L, but chronic toxicity may be seen in patients treated with the drug over long periods. Auditory toxicity may be potentiated by concurrent treatment with potent diuretics like ethacrynic acid. If tinnitus – which usually heralds the onset of auditory injury – develops, the drug should be withdrawn. Neuromuscular blockade is seen particularly in patients receiving other muscle relaxants or suffering from myasthenia gravis and may be reversed by neostigmine.

InChI:InChI=1/C18H36N4O11/c19-2-6-10(25)12(27)13(28)18(30-6)33-16-5(21)1-4(20)15(14(16)29)32-17-11(26)8(22)9(24)7(3-23)31-17/h4-18,23-29H,1-3,19-22H2/t4-,5+,6-,7-,8+,9-,10-,11-,12+,13-,14-,15+,16-,17-,18-/m1/s1

Synthetic route

Kanamycin A sulfate (3847-27-6, 25389-94-0, 64013-70-3, 81129-79-5, 84278-20-6, 94108-19-7, 94237-36-2) → kanamycin A (59-01-8)

Conditions	Yield
With Amberlite IRA-400-OH In water	91%
With Amberlite IRA-400 -OH In water
With Amberlite-IRA 400 (OH-)

C34H46N4O16 → kanamycin A (59-01-8) + 1-deamino-1-dehydro-1-hydroxyiminokanamycin A

Conditions	Yield
With hydrogen; acetic acid; palladium In water under 760 Torr; for 2h; Ambient temperature;	A 4.7% B 83%

6'-N-hydroxykanamicyn A (sulfate) (98084-09-4) → kanamycin A (59-01-8)

Conditions	Yield
With hydrogenchloride; hydrogen; platinum(IV) oxide In water under 2660 Torr; for 2h; Ambient temperature; Yield given;

di-tert-butyl ((1S,3R,4S,5R,6R)-4-(((2S,3R,4S,5S,6R)-4-((tert-butoxycarbonyl)amino)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-6-(((2R,3R,4S,5S,6R)-6-(((tert-butoxycarbonyl)amino)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-5-hydroxycyclohexane-1,3-diyl)dicarbamate (80860-34-0) → kanamycin A (59-01-8)

Conditions	Yield
tetrafluoroboric acid at 20℃; for 0.1h;

1-deamino-1-dehydro-1-hydroxyiminokanamycin A → 1-epi-kanamycin A (81076-65-5) + kanamycin A (59-01-8)

Conditions	Yield
With ammonium hydroxide; hydrogen; nickel under 2280 Torr; for 5h; Ambient temperature;

3,6'-bis(N-benzyloxycarbonyl)-3"-N-(trifluoroacetyl)kanamycin A (74256-73-8) → kanamycin A (59-01-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 86 percent / sodium tungstate dihydrate, aq. H2O2 / various solvent(s) / Ambient temperature 2: aq. NH4OH / various solvent(s) / Ambient temperature 3: 4.7 percent / H2, AcOH / Pd black / H2O; various solvent(s) / 2 h / 760 Torr / Ambient temperature View Scheme
Multi-step reaction with 4 steps 1: 86 percent / sodium tungstate dihydrate, aq. H2O2 / various solvent(s) / Ambient temperature 2: aq. NH4OH / various solvent(s) / Ambient temperature 3: 83 percent / H2, AcOH / Pd black / H2O; various solvent(s) / 2 h / 760 Torr / Ambient temperature 4: H2, aq. NH4OH / Raney Ni / 5 h / 2280 Torr / Ambient temperature View Scheme

C34H46N4O16 → kanamycin A (59-01-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 83 percent / H2, AcOH / Pd black / H2O; various solvent(s) / 2 h / 760 Torr / Ambient temperature 2: H2, aq. NH4OH / Raney Ni / 5 h / 2280 Torr / Ambient temperature View Scheme

3,6'-bis(N-benzyloxycarbonyl)-1-deamino-1-dehydro-1-hydroxyimino-3"-N-(trifluoroacetyl)kanamycin A → kanamycin A (59-01-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NH4OH / various solvent(s) / Ambient temperature 2: 4.7 percent / H2, AcOH / Pd black / H2O; various solvent(s) / 2 h / 760 Torr / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: aq. NH4OH / various solvent(s) / Ambient temperature 2: 83 percent / H2, AcOH / Pd black / H2O; various solvent(s) / 2 h / 760 Torr / Ambient temperature 3: H2, aq. NH4OH / Raney Ni / 5 h / 2280 Torr / Ambient temperature View Scheme

2'-oxokanamycin → kanamycin A (59-01-8)

Conditions	Yield
With His-tagged NADPH-dependent reductase; potassium chloride; glycerol; NADPH at 28℃; pH=7.5; Tris-HCl buffer; Enzymatic reaction; stereoselective reaction;

C22H43N5O13*2H2O4S → kanamycin A (59-01-8)

Conditions	Yield
With sodium hydroxide In water at 20℃; for 20h; Reagent/catalyst; Solvent; Temperature;

4‐nitrophenyl N‐benzylcarbamate (124068-97-9) + kanamycin A (59-01-8) → 1-benzyl-3-{5-(3-benzyl-ureido)-4-[4-(3-benzyl-ureido)-3,5-dihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy]-2-[6-(3-benzyl-ureidomethyl)-3,4,5-trihydroxy-tetrahydro-pyran-2-yloxy]-3-hydroxy-cyclohexyl}-urea (1054616-53-3)

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 20℃; for 3h;	93%

kanamycin A (59-01-8) + 1,3-di(tert-butyloxycarbonyl)-2-(trifluoromethylsulfonyl)guanidine (207857-15-6) → guanidinoboc8-kanamycin

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 20℃;	91%

kanamycin A (59-01-8) + 1,3-di(tert-butyloxycarbonyl)-2-(trifluoromethylsulfonyl)guanidine (207857-15-6) → C62H108N12O27 (290360-47-3)

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 20℃; for 72h;	91%

di-tert-butyl dicarbonate (24424-99-5) + kanamycin A (59-01-8) → di-tert-butyl ((1S,3R,4S,5R,6R)-4-(((2S,3R,4S,5S,6R)-4-((tert-butoxycarbonyl)amino)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-6-(((2R,3R,4S,5S,6R)-6-(((tert-butoxycarbonyl)amino)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-5-hydroxycyclohexane-1,3-diyl)dicarbamate (80860-34-0)

Conditions	Yield
In water; N,N-dimethyl-formamide at 60℃; for 5h;	91%
With sodium carbonate In methanol; water at 20℃; for 4h;	90%
In water; dimethyl sulfoxide at 70℃; for 20h;	84%
In water; dimethyl sulfoxide at 70℃; for 20h;	84%
With triethylamine In water; N,N-dimethyl-formamide at 60℃; for 6h; Inert atmosphere;	76%

2,2-dimethylpropanoic anhydride (1538-75-6) + kanamycin A (59-01-8) → di-tert-butyl ((1S,3R,4S,5R,6R)-4-(((2S,3R,4S,5S,6R)-4-((tert-butoxycarbonyl)amino)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-6-(((2R,3R,4S,5S,6R)-6-(((tert-butoxycarbonyl)amino)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-5-hydroxycyclohexane-1,3-diyl)dicarbamate (80860-34-0)

Conditions	Yield
In methanol; water	90%

benzyl chloroformate (501-53-1) + kanamycin A (59-01-8) → 1,3,6',2''-tetra-N-benzyloxycarbonyl-kanamycin A (5605-66-3)

Conditions	Yield
With sodium carbonate In acetone at 20℃; for 18h;	84%
With sodium carbonate In water Yield given;

C16H20N2O4S2 + kanamycin A (59-01-8) → amikacin (37517-28-5)

Conditions	Yield
Stage #1: kanamycin A With chloro-trimethyl-silane; 1,1,1,3,3,3-hexamethyl-disilazane In acetonitrile Reflux; Stage #2: C16H20N2O4S2 In acetone; acetonitrile at 0 - 5℃; for 1h; Stage #3: With hydrogenchloride In water; acetone; acetonitrile for 1h; pH=2 - 3; Solvent; Reagent/catalyst; Temperature;	83%

C31H30N3O12P (1608113-35-4) + kanamycin A (59-01-8) → 5'-O-(dibenzylphosphate)-3'-O-(kanamycin A carbamate)thymidine

Conditions	Yield
With triethylamine In 1,4-dioxane; water at 0 - 20℃; for 16h;	82%

N-(phenylacetyl)oxysuccinimide (23776-85-4) + kanamycin A (59-01-8) → tetra N-phenylacetyl-kanamycin A (1352640-83-5)

Conditions	Yield
With sodium hydrogencarbonate In water; N,N-dimethyl-formamide at 20℃;	81%

N,N'-bis( tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine (152120-54-2, 862686-58-6, 1143572-00-2) + kanamycin A (59-01-8) → C29H54N6O15

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane; water at 20℃; for 5h;	78%

5-benzoyl-3-(cyclopent-1-en-1-yl)-5-phenyl-1,5-dihydro-4H-pyrazol-4-one + kanamycin A (59-01-8) → C25H40N4O12

Conditions	Yield
In dimethyl sulfoxide at 50℃; for 72h;	77%

kanamycin A (59-01-8) + Boc-S → di-tert-butyl ((1S,3R,4S,5R,6R)-4-(((2S,3R,4S,5S,6R)-4-((tert-butoxycarbonyl)amino)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-6-(((2R,3R,4S,5S,6R)-6-(((tert-butoxycarbonyl)amino)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-5-hydroxycyclohexane-1,3-diyl)dicarbamate (80860-34-0)

Conditions	Yield
With triethylamine In 1,4-dioxane; water for 24h; Ambient temperature;	75%

kanamycin A (59-01-8) + N-(t-butoxycarbonyloxy)-5-norbornene-endo-2,3-dicarboximide → 6'-N-(tert-Butoxycarbonyl)kanamycin A

Conditions	Yield
In dimethyl sulfoxide Ambient temperature;	70%

benzoyl chloride (98-88-4) + kanamycin A (59-01-8) → tetra N-benzoyl-kanamycin A

Conditions	Yield
With sodium carbonate In methanol; water at 0℃;	68%

N-(Benzyloxycarbonyloxy)succinimide (13139-17-8) + kanamycin A (59-01-8) → 1,3,6',2''-tetra-N-benzyloxycarbonyl-kanamycin A (5605-66-3)

Conditions	Yield
With sodium hydrogencarbonate In water; N,N-dimethyl-formamide at 20℃;	66%

p-methoxybenzyl-S-(4,6-dimethylpyrimidine-2-yl)thiocarbonate (93801-72-0) + kanamycin A (59-01-8) → 3,6'-di-N-p-methoxybenzyloxycarbonyl kanamycin A (93801-63-9)

Conditions	Yield
With nickel diacetate In dimethyl sulfoxide for 0.5h;	65%

azidoacetic acid succinimidyl ester + kanamycin A (59-01-8) → C20H37N7O12 (1220984-53-1)

Conditions	Yield
With potassium carbonate In methanol; water for 20h;	55%

N-(Benzyloxycarbonyloxy)succinimide (13139-17-8) + kanamycin A (59-01-8) → 3,6'-bis-N-benzyloxycarbonylkanamycin A (66567-24-6)

Conditions	Yield
Stage #1: kanamycin A With zinc diacetate In dimethyl sulfoxide Inert atmosphere; Stage #2: N-(Benzyloxycarbonyloxy)succinimide In dimethyl sulfoxide Inert atmosphere;	50%
With zinc diacetate In dimethyl sulfoxide Inert atmosphere;	50%
Stage #1: kanamycin A With zinc diacetate In dimethyl sulfoxide at 20℃; for 12h; Stage #2: N-(Benzyloxycarbonyloxy)succinimide In dimethyl sulfoxide for 2h;

kanamycin A (59-01-8) → Kanamycin A-3'-phosphate (17029-36-6)

Conditions	Yield
With Tmed buffer; magnesium acetate In water for 12h; aminoglycoside phosphotransferase;	44%

acetone O-<(vinyloxy)carbonyl>oxime (139705-38-7) + kanamycin A (59-01-8) → {4-(3,5-dihydroxy-6-hydroxymethyl-4-vinyloxycarbonylamino-tetrahydro-pyran-2-yloxy)-3-hydroxy-2-[3,4,5-trihydroxy-6-(vinyloxycarbonylamino-methyl)-tetrahydro-pyran-2-yloxy]-5-vinyloxycarbonylamino-cyclohexyl}-carbamic acid vinyl ester (791064-46-5)

Conditions	Yield
With sodium hydroxide In phosphate buffer at 0℃; for 5h; pH=8.0;	37%

2,4,6-trinitrobenzensulfonate (2508-19-2) + kanamycin A (59-01-8) → tetra N-(2,4,6-trinitrophenyl)kanamycin A

Conditions	Yield
With pyridine In water at 70℃; for 0.333333h;	29%

N-[(S)-4-benzyloxycarbonylamino-2-hydroxy-butyryloxy]succinimide (40371-52-6) + kanamycin A (59-01-8) → C30H49N5O15 + C42H62N6O19

Conditions	Yield
Stage #1: kanamycin A With zinc diacetate In water; N,N-dimethyl-formamide at 20℃; for 16h; Stage #2: N-[(S)-4-benzyloxycarbonylamino-2-hydroxy-butyryloxy]succinimide In water; N,N-dimethyl-formamide for 24h;	A 12% B 16%

acetic anhydride (108-24-7) + kanamycin A (59-01-8) → tetra-N-hepta-O-acetylkanamycin A (144727-29-7)

Conditions	Yield
With pyridine

kanamycin A (59-01-8) + ATP (56-65-5) → C28H48N9O17P

Conditions	Yield
at 37℃; aminoglycoside-4'-nucleotidyltransferaze of Bacillus brevis, MgCl2, potassium phosphate buffer (pH 6.0);

kanamycin A (59-01-8) → C18H32(2)H4N4O11*4ClH

Conditions	Yield
With diclazuril In water-d2

Upstream product

• 98084-09-4 6'-N-hydroxykanamicyn A (sulfate) 
• 80860-34-0 di-tert-butyl ((1S,3R,4S,5R,6R)-4-(((2S,3R,4S,5S,6R)-4-((tert-butoxycarbonyl)amino)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-6-(((2R,3R,4S,5S,6R)-6-(((tert-butoxycarbonyl)amino)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-5-hydroxycyclohexane-1,3-diyl)dicarbamate 
• 74256-73-8 3,6'-bis(N-benzyloxycarbonyl)-3-N-(trifluoroacetyl)kanamycin A 
• 3847-27-6 Kanamycin A sulfate 

Downstream Products

• 75178-77-7 6',3-N,N-bis(tert-butyloxycarrbonyl)kanamycin A 
• 31657-07-5 6'-acetylkanamycin 
• 80860-34-0 di-tert-butyl ((1S,3R,4S,5R,6R)-4-(((2S,3R,4S,5S,6R)-4-((tert-butoxycarbonyl)amino)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-6-(((2R,3R,4S,5S,6R)-6-(((tert-butoxycarbonyl)amino)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)oxy)-5-hydroxycyclohexane-1,3-diyl)dicarbamate 
• 791064-46-5 {4-(3,5-dihydroxy-6-hydroxymethyl-4-vinyloxycarbonylamino-tetrahydro-pyran-2-yloxy)-3-hydroxy-2-[3,4,5-trihydroxy-6-(vinyloxycarbonylamino-methyl)-tetrahydro-pyran-2-yloxy]-5-vinyloxycarbonylamino-cyclohexyl}-carbamic acid vinyl ester 
• 225243-32-3 C₄₂H₈₄N₂₀O₁₅ 
• 74256-73-8 3,6'-bis(N-benzyloxycarbonyl)-3-N-(trifluoroacetyl)kanamycin A 
• 75178-74-4 C₂₁H₄₂N₆O₁₃ 

Relevant academic research and scientific papers

Method for recovering kanamycin A from amikacin synthesis solution

The invention discloses a method for recovering kanamycin A from an amikacin synthesis solution. The amikacin synthesis solution mainly comprises K29, kanamycin A and amikacin. The method for recovering kanamycin A comprises the following steps: 1) purifying the amikacin synthesis solution through a macro-porous cation exchange resin to obtain kanamycin A, amikacin and K29 respectively; 2) hydrolyzing the K29, obtained by purification in step 1), by using an alkali to obtain kanamycin A; and 3) mixing the kanamycin A obtained in the step 1) with the kanamycin A obtained in step 2). The methodallows a part of kanamycin A to be directly recovered from the amikacin synthesis solution, and allows the remaining kanamycin A to be recovered by simple synthesis steps of other recycled components,so the cost is greatly reduced, a reaction waste liquid is reduced, and the pollution to the environment is reduced; and the synthesis reaction of the kanamycin A has the advantages of mild conditions, easiness in separation and purification of the product, and no special equipment requirements.

Synthesis of ring II/III fragment of Kanamycin: A new minimum structural motif for aminoglycoside recognition

A novel protocol has been established to prepare the kanamycin ring II/III fragment, which has been validated as a minimum structural motif for the development of new aminoglycosides on the basis of its bactericidal activity even against resistant strains. Furthermore, its ability to act as a AAC-(6′) and APH-(3′) binder, and as a poor substrate for the ravenous ANT-(4′), makes it an excellent candidate for the design of inhibitors of these aminoglycoside modifying enzymes.

COMPOUNDS AND METHODS FOR MODULATING RNA FUNCTION

The present invention provides compounds, compositions thereof, and methods of using the same.

COMPOUNDS AND METHODS OF TREATING RNA-MEDIATED DISEASES

The present invention provides compounds, compositions thereof, and methods of using the same.

The last step of kanamycin biosynthesis: Unique deamination reaction catalyzed by the α-ketoglutarate-dependent nonheme iron dioxygenase KanJ and the NADPH-dependent reductase KanK

Mystery solved: Using heterologous expression, the activities of two enzymes exclusively belonging to the kanamycin biosynthetic pathway have been identified in vitro. A distinctive reaction mechanism (see scheme) to produce kanamycin is proposed and the previously unknown catalytic deamination activity of KanJ dioxygenase is uncovered. Copyright

NEW AMINOGLYCOSIDE COMPOUNDS AND DERIVATIVES THEREOF

New amino glycoside compounds or derivatives thereof having at least one sugar moiety and which comprise two or more cyclic structures capable of forming “charmed” structural features at physiological pH, and which have binding affinities for RNA and protein structures and may be used as therapeutic or screening or diagnostic agents and the like.

Site-specific aminoglycoside derivatives and their use in immunodiagnostic assays

A method of making a derivatized aminoglycoside includes reacting an aminoglycoside with at least 2 equivalents of a divalent metal ion in an aprotic solvent to complex two neighboring amino group and hydroxyl group pairs; reacting the non-complexed amino groups with a protecting reagent to provide protecting groups; removing the divalent metal ion to provide two unprotected amino groups; reacting one of the unprotected amino groups with a reactive substance containing an linker, a carrier, or a label; and removing the protecting groups. This method can be used to produce novel compounds and reagents.

Process for preparing amikacin

Described is a process for preparing Amikacin wherein 1-N-(L(-)γ-benzyloxycarbonylamino-α-hyroxybutyryl)-3,6'-di-N-benzyloxycarbonyl-Kanamycin A suspended in a suitable solvent, is treated with an aqueous solution of formic acid in the presence of a catalyst; the reaction mixture is charged on a ion exchange resin column to yield the desired product. Among the side-products Kanamycin A is obtained which is per se useful.

Process for preparing amikacin

Described is a process for preparing Amikacin wherein 1--N-(L(-)-γ-benzyloxycarbonylamino-α-hydroxybutyryl)-3,6?-di--N-benzyloxycarbonyl-Kanamycin A suspended in a suitable solvent, is treated with an aqueous solution of formic acid in the presence of a catalyst; the reaction mixture is charg-ed on a ion exchange resin column to yield the desired pro-duct. Among the side-products Kanamycin A is obtained which is per seuseful.

SYNTHESES OF METHYL 6-DEOXY-6-HYDROXYAMINO-α-D-GLUCOPYRANOSIDE, 6'-N-HYDROXYKANAMYCIN A, AND 6'-N-HYDROXYDIBEKACIN

Methyl-6-deoxy-6-hydroxyamino-α-D-glucopyranoside has been prepared from methyl 6-amino-6-deoxy-α-D-glucopyranoside via oxidation with hydrogen peroxide in the presence of sodium tungstate , followed by reduction with sodium cyanoborohydride in an acidic medium.Acetylation of the Z isomer of 2 gave a nitrile derivative.The above oxidation-reduction procedure was applied to kanamycin A and dibekacin, starting from the corresponding 6'-amino-N-tosyl derivatives.On treatment with sodium in liquid ammonia, 6'-deamino-6'-hydroxyimino-1,3,3''-tri-N-tosylkanamycin A gave the corresponding N-detosyl derivative in good yield with the 6'-aldoxime group remaining intact, but, with 6'-deamino-6'-hydroxyimino-1,3,2',3''-tetra-N-tosyldibekacin, the N-detosyl derivative (17) was obtained only by a very short reaction period.The antibacterial activities of 17 and 6'-N-hydroxydibekacin were demonstrated.