Page 130 - Medicinal Chemistry Self Assessment

2.6 Stereochemistry and Drug Action 119

have geometric isomers. Please note that the double bonds seen in the 1,4-dihydropyridine ring
of nifedipine reside in a six-membered ring and thus cannot participate in the formation of
geometric isomers.

Medicinal Chemistry Self-Assessment Book: Batch Two
Chapters 1.6 and 2.6
3. Shown below is the structure of fluvastatin, an HMG-CoA reductase inhibitor used to lower plasma

LDL levels. Fluvastatin contains two chiral centers, designated as 1 and 2. Using the structure of
Revised structure reflects chiral carbons #1 and #2.
fluvastatin and the Cahn-Ingold-Prelog (CIP) system, determine the R/S configurations for each of its
chiral centers.

H O 1
CO H
2
2 OH
H

CH
F 3
N
CH 3

Fluvastatin
Answer:
Answer

D
A
C
Chiral center 1 Chiral center 2 A
B B
D
C

Fluvastatin Fluvastatin

Using the CIP sequence rules for chiral center 1, the hydroxyl group (A) has the first priority because
oxygen always has priority over carbon. Carbon atoms B and C are identical because each is attached
4. Shown below is the enantiomer of fluvastatin. Which of the following properties/actions would be expected to
to one carbon atom and two hydrogen atoms. It is therefore necessary to examine the two adjacent
carbon atoms. The carbon atom adjacent to carbon C (O,O,O) has priority over the carbon atom adja-
be identical for fluvastatin and its enantiomer and which would be expected to be different?
cent to carbon B (O,C,H); thus, the final priority is hydroxyl group (A) > carbon atom C > carbon atom
B > hydrogen atom (D). The hydrogen atom is projected into the paper and located away from the
a. Percent ionization at a pH of 7.4
reader. Applying the above priorities reveals a clockwise orientation. Thus, the correct designation
for chiral center 1 is R.
Using the CIP sequence rules for chiral center 2, the hydroxyl group (A) once again has the first
H
O
priority, and the hydrogen atom (D) has the least priority. Carbon atom C (C,C,H) has priority over
CO H
2
carbon atom B (C,H,H); thus, the final priority is hydroxyl group (A) > carbon atom C > carbon atom
OH
H
F
N

Enantiomer of
Fluvastatin

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