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KHANG SINH PHENICCLORAMPHENICOL

O2N

NH

HO OH

O

ClCl

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CLORAMPHENICOL

D(-)threo: ng phn chat tnh

CHCl 2COH NHOH H

NO 2

CH 2OH CH2OH

NO 2

H OHHCl2HC CO HN

D(-)-threo1R,2R

L(+)-threo1S,2S

CH 2OH

NO 2

H OHH NH CO CHCl 2

D(-)-erythro1S,2R

HHO H

NO 2

CH 2OH

Cl2HC CO HN

L(+)-erythro1R,2S

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Cloramphenicol co the c tong hp hoan toabang phng phap hoa hoc t :

P-nitroacetophenon. Acetophenon. P-nitrobenzaldehyd. Styren.

Alcol cinamic.

IEU CHE

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NO 2

CHO

+CH 2 COOHNH2

NO 2

CHOHCHNH 2COOH

NO 2

CHOHCHNH 2COOCH 3

CH 3OH/HCl

acid D (+) tartric

NO 2

CCCOOCH 3

HHOH NH2

Cl CO

CHCl 2

NO 2

CCCOOCH 3

HHOH NHCOCHCl 2

NO 2

CCCONHNH 2

HHOH NHCOCHCl 2

NH 2-NH 2

NO 2

CCCO

HHOH NHCOCHCl 2

HNO 3 NaBH 4

N3

NO 2

CCCH 2OH

HHOH NHCOCHCl 2

cloramphenicol

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Nhom nitro thm

O2N

NH

HO OH

O

ClCl

TNH CHAT HOA HOC

- Kh ha diazo ha azoic ha

- Kh ha benzoyl ha to phc vi Fe 3+

R NO 2 + 4HCaCl 2

R NH OH

Cl C

O

C 6H5

R N CHO O

Fe3

purple

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Do nhom dicloacetyl Phan ng FUJIWARA ROSSun cach thuycloramphenicol vi pyridin va NaOH, mau o xuat hien.

O2N

NH

HO OH

O

ClClTNH CHAT HOA HOC

O 2N CH

OH

CHCH 2OH

NHC O

HCCl Cl

OH

O 2N C

OH

NH

HOH 2C

OCl

OH

O 2N C

OH

NH

HOH 2C

OOH

O 2N CNH

HOH 2C

OOH

(yellow)

CNH

HOH 2C

OO

N

H

O

OH2

CNH

HOH 2C

OO

NO

O

H(red)

Chem.Pharm.Bull 31(8)2737-2742 (1983)

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este palmitat, stearat khong ang, khong tan trong n

- este succinat, glicinat tan c dung lam thuoc tiem

TNH CHAT HOA HOCDo nhom alcol bac nha t

Chloramphenicolpalmitat

Chloramphenicolsodium succinat

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Thy phn trong mi trng kim

HOOC N N COOH

NO 2

CHO H

CH NHCH 2OH

C

O

CHCl 2

Dung dch NaOH,un nng

mu cam

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NO 2

CHO HCH NH

CH 2OH

CO

CHCl 2

h

HCl

O 2N CHO

O 2N COOH

HOOC N=N

O

COOH

H2N CH CH

OH

CH 2OH

HN COCH 3

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KIM NGHIM

IDENTIFICATIONFirst identificationA, B.Second identificationA, C, D, E.

A. Melting point ( 2.2.14): 149 C to 153 C.

B. Examine by infrared absorption spectrophotometry ( 2.2.24), comparingwith the spectrum obtained with chloramphenicol CRS. NO 2

CHO HCH NHCH 2OH

CO

CHCl 2

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KIM NGHIM

IDENTIFICATIONFirst identificationA, B.Second identificationA, C, D, E.

A. Melting point ( 2.2.14): 149 C to 153 C.

B. Examine by infrared absorption spectrophotometry ( 2.2.24), comparingwith the spectrum obtained with chloramphenicol CRS.

C. Examine the chromatograms obtained in the test for related substances.

D. Dissolve about 10 mg in 1 ml of alcohol (50 per cent V/V) R, add 3 ml of a10 g/l solution of calcium chloride R and 50 mg of zinc powder R and heat ona water-bath for 10 min. Filter the hot solution and allow to cool. Add 0.1 mlof benzoyl chloride R and shake for 1 min. Add 0.5 ml of ferric chloridesolution R1 and 2 ml of chloroform R and shake. The aqueous layer iscoloured light violet-red to purple.

E. To 50 mg in a porcelain crucible add 0.5 g of anhydrous sodium carbonateR. Heat over an open flame for 10 min. Allow to cool. Take up the residuewith 5 ml of dilute nitric acid R and filter. To 1 ml of the filtrate add 1 ml of

water R. The solution gives reaction (a) of chlorides ( 2.3.1).

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TESTSAcidity or alkalinity

Specific optical rotation (2.2.7)

Related substances

Chlorides (2.4.4)

ASSAYDissolve 0.100 g in water R and dilute to 500.0 ml with the samesolvent. Dilute 10.0 ml of this solution to 100.0 ml with water R.Measure the absorbance (2.2.25) at the maximum at 278 nm.

Calculate the content of C 11 H12 Cl2N2O5 taking the specific absorbance

to be 297.

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ket dnh 50 S cua ribosomt-ARN khong giai mac ngan chan qua trnh sinh tong hp protein

C CHE TAC ONG

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Pho khang khuan tng oi rong nhng b e khangrat nhanh, chu yeu tac dung tren vi khuan gram am: Vi khuan gram dng:Streptococcus

pneumoniae , Corynebacterium. Vi khuan gram am:Neisseria gonorhoea, N.

eningitides, Salmonella, shigella, Haemophilus,

Campylobacter. Vi khuan k kh: Clostridium, Bacteroides

O2N

NH

HO OH

O

ClCl

PHO KHANG KHUAN

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S e khang qua trung gian plasmid Vi khuan tiet ra acetyl tranferase tao dan chat

acetyl hoa cua cloramphenicol, dan chat aykhong ket hp c vi ribosom cua vi khuan,lam mat tac dung cua thuoc.

O2N

NH

HO OH

OCl

Cl

S E KHANG

OC TNH VA TAI BIEN

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Roi loan tieu hoa: buon non, non ma va tieu

Diet tap khuan ruot: co the b boi nhiem namniem mac (mieng va am ao). oc tnh oi vi mau:

Roi loan tuy xng (dung lau ngay, lieu cao), cophuc hoiThieu mau khong tai tao (pancytopenia) ch xaybiet nhng benh nhan ac ng do di truyen (khoang 1/30000), khong phuc hoi

OC TNH VA TAI BIEN

* Tai bien loai Herxheimer

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Cloramphenicol ch c dung khi can thiet Dung cloramphenicol chu yeu trong sot thng

va pho thng han, nhiem trung Haemophilusla khi chung nh v trong nao.

Dung trong nhiem trung k kh ac biet nhiemdo Bacteroides.

dang thuoc nho mat, cong dung cuacloramphenicol c gii han trong nhng nhietrung cac vi khuan nhay cam.

CH NH

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Khuech tan tot qua mang nao va dch nao tuy t b chuyen hoa di dang glucuronic, Bai xuat qua nc tieu (50-70% con hoat tnh) Pho khang khuan tng t cloramphenicol, Dung c

yeu cho nhiem trung tieu, ac biet benh lau.

SO 2

HN

OH

OH

O

Cl

Cl

CH 3

THIAMPHENICOL