??????????: ?? ?????? Streptomyces ??? ???? ??????? ????????????? ?? ???????? ????????.

1
????????????

• ?????????? ?? ?????? Streptomyces ??? ????
  ??????? ????????????? ?? ???????? ????????.
• ????????? ????????????????????.
• ???????? ?????????, ???? ? ?-?? ??? ???????
  ?????? ???????????? ????????? ? ??????????? ???
  ???????????? ?????? ? ????????? ??????? ??????
  ???.

2
.
?4, ?4?, ?5, ?5?, ?6, ?12? ???????????
??????????? ?2 ?????? N-???? ?3, ?12 ??????
??-????? ?4 ??????? N-???? ?10 ???????
??-?????.
3
?????????/?????????

• ?????? ????
• ????? ????? ??????? ? ?, ????????? ????????? ??
  ?????????.
• ???????? ????? ??? ????? ?????????.
• ??????? ??? ?????? ??? ?2-???????? ?????????.
• ???????????????? ?? ??????? ???? ????????
  ???????????.
• ????????????????? ?? ??????? ???? ???? ????????
  ??????? ????? ?????????? ??? ???? ??????????,
  ????? ???????????? in vivo (Rolitetracycline).
• ?12 ?????? ????????? ??????????.
• ?????????? ??? ?12?-????????? ??????????.
• ????????????-????????? ??????????.

4
 
5
Epitetracyclines
???????????? ??? ?4 ? ?-?? ??? ?????? ??
????????, ????? ??-????? ?????????.
6
(No Transcript)
7
????????? ?? ????????

• ??????????????? ???????????. ????????????????
  ????????.
• ??????????? ???????????? ?? ????????? ?????? ??
  ???????? ???? ?????????? ??????????? ??
  ???????????? ??? ? ??????????.

8
Tetracycline
Ph Eur

• Streptomyces aureofaciens

(4S,4aS,5aS,6S,12aS)-4-dimethylamino- 1,4,4a,5,5a,
6,11,12a-octahydro-3,6,10,12,12a- pentahydroxy-6-m
ethyl-1,11- dioxo-2-naphthacene-2-carboxamide
hydrochloride
Ph Eur
Tetracycline Hydrochloride
9
Chlortetracycline

• 1948 S. aureofaciens

Chlortetracycline Hydrochloride
Ph Eur
10
Rolitetracycline prodrug
N- (pyrrolidinomethyl)tetracycline
11
(No Transcript)
12
Oxytetracycline
Str. rimosus
(4S,4aR,5S,5aR,6S,12aS)-4-(dimethylamino)-1,4,4a,
5,5a,6,11,12a-octahydro- 3,5,6,10,12,12a-hexahydro
xy-6-methyl-1,11- dioxo-2-naphthacenecarboxamide
Ph Eur
Oxytetracycline Hydrochloride
(4S,4aR,5S,5aR,6S,12aS)-4-(Dimethylamino)-3,5,6,10
,12,12a-hexahydroxy- 6-methyl-1,11-dioxo-1,4,4a,5,
5a,6,11,12a-octahydrotetracene-2-carboxamide
hydrochloride
13
Oxytetracycline Calcium

• BP 2007

Ph Eur
Oxytetracycline Dihydrate
14
Methacycline
(4S,4aR,5S,5aR,12aS)-4-dimethylamino-1,4,4a,5,5a,6
,11,12a-octahydro- 3,5,10,12,12a-pentahydroxy-6-me
thylene-1,11 -dioxo-2-naphthacenecarboxamide ?????
?? ??????????? ?? Oxytetracycline 1961.
15
Doxycycline
Substance obtained from oxytetracycline or
metacycline or by any other means.
(4S,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-1,4,4a,
5,5a,6,11,12a-octahydro- 3,5,10,12,12a-pentahydrox
y-6-methyl-1,11-dioxo-2- naphthacenecarboxamide
monohydrate
Ph Eur
Doxycycline Monohydrate
(4S,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-3,5,10,1
2,12a-pentahydroxy- 6-methyl-1,11-dioxo-1,4,4a,5,5
a,6,11,12a-octahydrotetracene-2-carboxamide
monohydrate
16
?????????

• ??????
• ????? ???????? ??????? ????????(12, 14 ??? 16
  ?-?????).
• ????-?????.
• ?????????? ???????? ????? ?????.
• ???????? ????? ???????, ???????? ???? ,
  ???????????????? ????????, ???????? ?????????
  ?????? ?? ????????.

17
?????????

• Actinomyces 1950 Picromycin
• 1952 Erythromycin

?3-?????????? ???????? ?????????
18
Erythromycin

• Ph Eur

Mixture of macrolide antibiotics produced by a
strain of Streptomyces erythreus, the main
component being (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R
)-4-(2,6-dideoxy-3-C-methyl-3-O-methyl-a-L-ribo-h
exopyranosyl)oxy-14-ethyl-7,12,13-trihydroxy-3,5,
7,9,11,13-hexamethyl-6-(3,4,6-trideoxy-3-dimethyl
amino-b-D-xylo-hexopyranosyl)-oxyoxacyclotetradec
ane-2,10-dione (erythromycin A).
Content sum of the contents of
erythromycin A, erythromycin B and erythromycin
C 93.0 per cent to 102.0 per cent (anhydrous
substance), erythromycin B maximum 5.0
per cent, erythromycin C maximum 5.0 per
cent.
19
????????? 1957

• ??????????? 1965
• Erythromycin ? ??-???????? ? ????????? ?????, ??
  ????????? 80 ?? ??????????? ?? Erythromycin ?.
• Erythromycin ? ????????? ????????? ?????????? ??
  Erythromycin ?.

20
??????? ???????????

• ??? ?? ????? ???????????? ??? ????
• ??? ??????
• ????????? ??????????.
• Erytromycin Stearate
• Erytromycin Ethylsuccinate
• Erytromycin Estolate
• Erythromycin Lactobionate

Ph Eur
21
Erytromycin Stearate

• ??? ?? ??3-(??2)16-????, ??????????? ??? ????,
  ??????? ? ????????? ?????, ????????? ? ??????? ?
  ?????? ?? ????????? ? ????????? ?? ?? ?????????.

Erytromycin Ethylsuccinate ??-??????? ?? ?????
??????? ? ?????????????? ? ???????? ????? ??
????????? ????????. ????? ?????????, ??????? ?
????????? ?????, ??????????? ???
????. Erytromycin Estolate ??-??????? ?? ?????
??????? ? ?????????????? ? ????????? ?-??,
???????????? (?12?25?SO3H), ????????? ??? ????.

Erythromycin 2-propanoate dodecyl sulfate (salt).

22
Erythromycin Lactobionate????????? ??? ????.
23
Clarithromycin

• 6-methyl ether of Erytromycin
• ??????????????

Ph Eur
(3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-4-(2,6-Dideox
y-3-C-methyl-3- O-methyl-a-L-ribo-hexopyranosyl)ox
y-14-ethyl-12,13- dihydroxy-7-methoxy-3,5,7,9,11,
13-hexamethyl-6-3,4,6-trideoxy-3- (dimethylamino
)-b-D-xylo-hexopyranosyloxyoxacyclotetradecane-
2,10-dione (6-O-methylerythromycin A)
24
Oleandomycin

• Str. Antibioticus
• ???????????, ??????

25
Spiramycin

• Str. ambofaciens

26
???????????????

• ???????????? ????????
• ????? ???????
• ????????? ?????????? ???????
• ?????????? ???????? ????? ??????

27
???????????????

• Streptomycin ???-???????? 4,5-7 ??
• Str. griseus

Ph Eur
Streptomycin Sulphate
bisN,N-bis(aminoiminomethyl)-4-O-5-deoxy-2-O-
2-deoxy-2-(methylamino)-a-L-glucopyranosyl-
3-C-formyl-a-L- lyxofuranosyl-D-streptamine
trisulphate
28
Neomycin 1949

• Str. fradiae

Neomycin Sulphate
Ph Eur
2-deoxy-4-O-(2,6-diamino-2,6-dideoxy-a-D-glucopyra
nosyl)- 5-O-3-O-(2,6-diamino-2,6-dideoxy-b-L-idop
yranosyl)-b-D-ribofuranosyl -D-streptamine
(neomycin B)
29
Kanamycin

• Str. kanamyceticus

Ph Eur
Kanamycin Sulphate (?)
6-O-(3-amino-3-deoxy-a-D-glucopyranosyl) -4-O-(6-a
mino-6-deoxy-a-D- glucopyranosyl) -2-deoxy-D-strep
tamine sulphate
30
Amikacin??????????????
Amikacin Sulphate
Ph Eur
6-O-(3-amino-3-deoxy-a-D-glucopyranosyl)-4- O-(6-a
mino-6-deoxy-a-D- glucopyranosyl)-1-N- (2S)-4-ami
no-2-hydroxybutanoyl-2-deoxy-D-streptamine
sulphate
31
Ph Eur Gentamicin Sulphate

• Mixture of the sulphates of antimicrobial
  substances produced by Micromonospora purpurea,
  the main components being gentamicins C1, C1a,
  C2, C2a and C2b.

32
Gentamycin 1958
33
Tobramycin 1976

• Str. tenebrarius

34
???????? ????? ??????????
Ph Eur

• Chloramphenicol

Streptomyces venezuelae
2,2-dichloro-N-(1R,2R)-2-hydroxy-1-(hydroxymethyl
)-2- (4-nitrophenyl)ethylacetamide
35
Chloramphenicol Palmitate

• Ph Eur

(2R,3R)-2-(dichloroacetyl)amino-3-hydroxy-3- (4-
nitrophenyl)propyl hexadecanoate
36
Chloramphenicol Sodium Succinate

• Ph Eur

Chloramphenicol sodium succinate, a mixture in
variable proportions of sodium
(2R,3R)-2-(dichloroacetyl)amino-3-hydroxy-3- (4-
nitrophenyl)propyl butanedioate (3 isomer) and
of sodium (1R,2R)-2-(dichloroacetyl)amino-3-hyd
roxy- 1-(4-nitrophenyl)propyl butanedioate (1
isomer).
37
???????????,????????? ???? ?????????????
???????? ???????? ?? ???????????.????
???????????????? ??? ???????????? ?????.

• Lincomycin

Ph Eur
Lincomycin Hydrochloride
Streptomyces lincolnensis var. lincolnensis
6,8-dideoxy-6-(2S,4R)-1-methyl-4-propylpyrroli
din- 2-ylcarbonylamino-1-thio-D-erythro-a-D-gal
acto- octopyranoside hydrochloride
38
Clindamycin
??????????????
Ph Eur
Clindamycin Hydrochloride
Methyl 7-chloro-6,7,8-trideoxy-6-(2S,4R)-1-meth
yl-4- propylpyrrolidin-2-ylcarbonylamino-1-thio
- L-threo-a-D-galacto- octopyranoside
hydrochloride
39
Clindamycin Phosphate

• Ph Eur

methyl 7-chloro-6,7,8-trideoxy-6-(2S,4R)-1-meth
yl-4- propylpyrrolidin-2-ylcarbonylamino- 1-thi
o-L-threo-a-D-galacto- octopyranoside
2-(dihydrogen phosphate)