Chemistry Reference
In-Depth Information
Omeprazole is a chiral molecule. There is a chiral center at the sulfur
atom of the sulfoxide. Omeprazole exists as a racemic mixture of R and S
enantiomers. The active metabolite, the sulfenamide, loses this chiral center
and therefore the metabolite is achiral. Researchers studied the enantiomers,
originally isolating each by preparing diasteromeric salts with mandelic acid
and then separating by chromatography [37]. In humans, the S enantiomer of
omeprazole has the highest bioavailability and potency in inhibiting gastric
acid secretion due to stereoselective metabolism of omeprazole. In 2000 this
finding resulted in the launch of the drug as a single S enantiomer, esomepra-
zole, known as Nexium
®
.
OCH
3
CH
3
OCH
3
H
3
C
N
O
N
S
N
H
Omeprazole
OCH
3
CH
3
OCH
3
CH
3
H
3
C
H
3
C
N
N
HS Enzyme
S
S
S
Enzyme
N
N
NH
N
OCH
3
OCH
3
Sulfenamide derivative of omeprazole
OCH
2
CF
3
CH
3
OCH
3
OCHF
2
OCH
3
N
N
O
O
N
S
N
S
N
N
H
Lansoprazole
H
Pantoprazole
OCH
3
CH
3
OCH
2
CH
2
CH
2
OCH
3
OCH
3
H
3
C
CH
3
N
N
O
O
N
S
N
S
N
N
H
Esomeprazole
H
Rabeprazole
Omeprazole can be made by reaction of a substituted diaminobenzene
to make the benzoimidazole [38]. Alkylation of the thiol gives the sulfide
which is then oxidized to the sulfoxide, omeprazole. The omeprazole can
be separated into the two enantiomers. Preferably, asymmetric oxidation of
the sulfide is done to selectively prepare the S enantiomer, esomeprazole.
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