Page 131 - Medicinal Chemistry Self Assessment

120 Medicinal Chemistry Self Assessment

B > hydrogen atom (D). Unlike chiral center 1, the hydrogen atom of chiral center 2 is projected out
of the paper and located directly toward the reader. In situations like this, there are three options:
Answer:
(1) redraw the chiral center with the hydrogen projected into the paper while maintaining the
correct stereochemical orientation of all other groups;
(2) imagine that you are viewing the object from the other side of the paper; or
D
(3) use the given projection and make an alteration in your final answer.
A
C
Options 1 and 2 are often difficult for students to accomplish without producing errors; therefore,
Chiral center 1
option 3 is suggested. Initially “pretend” that the hydrogen atom (or the atom of lowest priority) IS
Chiral center 2
A
B
projected into the plane of the paper and apply the sequence rules. In this case, there is a clockwise
B
orientation that is consistent with the R isomer. Because it was necessary to invert the stereochem-
D
istry of the chiral center to do this, the correct designation is the exact opposite. In this case, chiral
C
center 1 has the S configuration.
4. Shown below is the enantiomer of fluvastatin. Which of the following properties/actions would
be expected to be identical for fluvastatin and its enantiomer and which would be expected to be
different?
Fluvastatin Fluvastatin
a. Hepatic metabolism

b. Water solubility
4. Shown below is the enantiomer of fluvastatin. Which of the following properties/actions would be expected to
c. Adverse effect profile
d. Active renal reabsorption by transport proteins
be identical for fluvastatin and its enantiomer and which would be expected to be different?
e. Potency (dosage given)
a. Percent ionization at a pH of 7.4
f. Percent ionization at a pH=7.4

H O
CO H
2
OH
H

F
N

Enantiomer of
Fluvastatin
Answer

Enantiomers have identical physical and chemical properties, with the exception of the direction

in which they rotate plane polarized light. Thus, water solubility and the percent ionization of the
carboxylic acid at a pH of 7.4 would be expected to be identical. The major difference and most
important aspect of enantiomers are their relative abilities to interact with three-dimensional
biological targets. Hepatic metabolism and active renal reabsorption depend on binding to metabo-
lizing enzymes and transport proteins, respectively, and would be expected to be different. Adverse
effects can be due to the interaction of these drug molecules with other biological targets and/or the

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