KIMIA FARMASI KUALITATIF II

ANTIBIOTICS
Dr. Friardi, Apt

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 Aminoglycosides
History
• 1944 Streptomycin
• 1957 kanamycin
• 1964 gentamicin
• 1967 tobramycin
• Amikacin & netilmicin

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Phsical and chemical properties

 Structure
 Water-soluble, stable in solution
 More active at alkaline than at acid
pH

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 Streptomycin

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streptomycin was discovered as the
fermentation product of Streptomyces griseus
 White powder. Hygroscopic. Very soluble in
water, practically insoluble in ethanol and ether.
 Streptomycin has a basic property according to
the appearance of the nitrogen containing
group (two guanidins and one N-methylamino)
that’s why easy creates salts.
 In a weak acidic medium streptomycin is
stable, but in strong acidic and especially in
basic medium it easy hydrolyzes on a
streptydin and streptobiozamine, which
decomposes on N-methyl-L-glucosamine and
L-streptos.
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Maltol (α-methyl-β-oxy-γ-piron)

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• Sakaguchi reaction on the remnants of
guanidines. Formation of a violet-red
colour, which appearances in a basic
medium under the action of α-naphthol
and concentrated sodium hypochlorite.
• Molish reaction on carbohydrates
(streptos). After acidic hydrolysis the
substance does not give reaction with α-
naphthol and concentrated sodium
hypochlorite in a basic solution. 9

Yellow colour.
• Weber Reagent (it is oxidized by sodium
nitroprusside Na[Fe(CN)5NO]
+K3[Fe(CN)6]+NaOH) – red colour
(guanidine residues)
• Brown colour with basic potassium
tetraiodomerrcurate (Nernst reagent)
and red sediment with copper-tartrate
reagent– Feling reagent; “silver mirror”
reaction (on aldehyde group)
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• Condensation with phenols in the presence
of concentrated sulfuric acid – aurine
dye;

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• Composition of Kanamycin is aglucone 2-
deoxystreptomine (meso-1,3-diamino 4,5,6-
trioxycyclohexan) and two saccharates - 3-
amino-3-deoxy-D-glucose and 6- аmino-6-
deoxy-D-glucose.
• Drug is obtained by the fermentation of
Streptomyces kanamycetis at 27-29 оС and
рН=7, the environment that contains starch
and soy flour.
• From the environment Kanamycin A, B and C
is extracted by an ion changers. 14
• Reaction on the aliphatic amino-
group of Kanamycin monosulfate – at
the heating with a ninhydrin solution
observed violet color.
• After acidic hydrolysis kanamycin and
amikacin give the reaction of the
reducing saccharides (Feling reagent.
Nernst, Tolens).

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• Bial’s reaction (pentos openning).
For the identification of Kanamycin monosulfate and neomycin
sulfate using a color reaction with a alcohol solution of an orcyn
(methylresorcinol) and concentrated hydrochloric acid at the
present of iron (III) chloride. Solution gets green colour.

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• Amykacin according to the amide group forms color complexes with
the hard metal’s salts (reaction with cobalt nitrate after sodium
hydroxide neutralization – violet).
• Amikacin at the heating with concentrated mineral acids forms from
the saccharides 5-aminomethylfurfural, which gives the colour
reaction with antron:

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MACROLIDES

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Modern classification
1. 14 – members: natural (erythromycin,
oleandomycin); prodrug (esther and erythromycin
salts, oleandomycin esthers); semi-synthetic
(roxithromycin, clarithromycin, dirithromycin,
josamycin, its active metabolite is 14-hydroxi
clarithromycin).
2. 15 – members: semi-synthetic (additional nitrogen
atom – azalides – azithromycin
3. 16 – members: natural (spiramycin (rovamycin),
midecamycin (macropen), semisynthetic
(midecamycin acetate (miocamycin). 22
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• Erythromycin is produced from a strain of the actinomycete
Saccharopolyspora erythraea.
• Erythromycin consists of aglucone erythrolide (14-members
lactone) and two sugars: cladynos (3-methyl-3-methoxy-2,6
didedeoxyhexopyranos) and deamine (pycrocin, 3-
dimethylamino-4,6- didedeoxyhexopyranos).
• Erythromycin – white crystalline substance bitter on taste,
• melting at 190-193 оС,
• soluble in water, freely soluble in ethanol, acetone and
chloroform.
• With concentrated H2SO4 gives red-brown color, аnd with
concentrated HCl – orange color that transfers into red after
puple.

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QUINOLONS

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Fluoroquinolones characters
• Pale yellow crystalline powder, norfloxacin
and ciprofloxacin - hygroscopic.
• Very slightly or practically insoluble in water,
soluble in alcohol and acetone.
• Norfloxacin is a photosensitive.
• Chlorides of ofloxacin and ciprofloxacin are
soluble in water and practically insoluble in
alcohol, acetone and methylene chloride.

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Fluoroquinolones identification
• IR, UV spectroscopy, TLC.
• Heterocyclic nitrogen atom is determined by
Dragendorff’s reagent, picric acid.
• Oxo-group is identified by the reactions of the
formation of oxime’s precipitation (reaction
with hydroxylamine), thiosemicarbazone
(reaction with thiosemicarbazide)
phenylhydrazone (reaction with
phenylhydrazine). 28
• Formation of the chelate complexes of a dark-red
color with Fe3+ ions:

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