Exam 1 - UCLA Chemistry and Biochemistry

Chemistry 14C Lecture 1 Spring 2013 Exam 1 Page 1
OK to use "Ph" anywhere on this exam where appropriate.
Exceeding the specified word limit on an answer will result in a point deduction for that answer.
Terfenadine and fexofenadine are antihistamines. Terfenadine appeared on the market first, but was superseded by
fexofenadine because the latter has a lower risk of causing cardiac arrthymia. Terfenadine is a prodrug, meaning that
terfenadine is not active until metabolized in the body, in this case, into fexofenadine. The structures of these
molecules can be found on the exam information page (the last exam page). The questions on this exam refer to
terfenadine and fexofenadine.
1. (3) Write the molecular formula (i.e., C 6 H 60 ) for fexofenadine.
2. (2) Write the name of the functional group formed when terfenadine is metabolized into fexofenadine.
3. (24) Write a number in each blank.
(a) Of the oxygen atoms in fexofenadine _______ are sp 3 , ________ and sp 2 , and ________ are sp.
(b) Fexofenadine has ________ atoms with p orbitals and ________ conjugated atoms.
(c) Fexofenadine has ________ lone pairs in total. Of these lone pairs _________ are delocalized by resonance.
(d) Of the sp 3 stereocenters in fexofenadine, _____ have an R configuration and _____ have an S configuration.
(e) The fexofenadine structure shown on the information page has ________ enantiomers and _________
diastereomers. There are ______ fexofendine stereoisomers that are also meso compounds.
4. (6) Fexofenadine is... Circle the one best answer in each set.
(a) Chiral Achiral Both Neither Cannot determine from given information
(b) Optically active Optically inactive Both Neither Cannot determine from given information
(c) Dextrorotatory Levorotatory Both Neither Cannot determine from given information
5. (2) Terfenadine may cause cardiac arrhythmia (abnormal electrical activity in the heart, often causing irregular
heartbeat). What can we conclude about the possible drug effects of terfenadine's enantiomer? Circle all that
apply.
(a) Causes stronger cardiac arrhythmia.
(b) Causes weaker cardiac arrhythmia.
(c) Causes cardiac arrthymia, but to what extent, we cannot predict.
(d) The enantiomer causes a much steadier heartbeat than is normally present.
(e) It cures cardiac arrhythmia, so terfenadine should be sold as a racemic mixture.
(f) None of these conclusions are valid.
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Chemistry 14C Lecture 1 Spring 2013 Exam 1 Page 2
Levamisole is an anthelminthic (i.e., it is used to treat worm infestations in humans
and animals). The molecule also causes some neurological stimulation, which
probably explains why ~80% of cocaine seized by the FDA in recent years was
found to be have been "cut" (i.e., mixed) with detectable levels of levamisole.
Cocaine cut with levamisole appears to be more toxic than cocaine itself.
N
Levamisole
N
S
6. (8) In each box below, draw one additional levamisole resonance contributor. Make your contributors as
significant as possible. Include all lone pairs and formal charges for contributors B and C.
N
N
S
Contributor A Contributor B Contributor C
7. (10) Now let's evaluate the relative significance of the contributors you drew in question 6. In each case, circle
"more significant than", "less significant than", or "equally significant as" as appropriate. If you've circled
"equally significant as" you are done with this part. If you've circled "more significant than" or "less significant
than" complete the statement by adding no more than ten words in each of the open spaces.
(a) Contributor B is more significant than / equally significant as / less significant than contributor A because
contributor B...
...whereas contributor A...
(b) Contributor C is more significant than / equally significant as / less significant than contributor A because
contributor C...
...whereas contributor A...
8. (4) Complete this drawing of the levamisole resonance hybrid by
adding all missing partial pi bonds. Use **all** significant
contributors to construct this hybrid. Do not include any δ + or δ -
charges to this drawing. Practice your answer on the back of an
exam page before you draw your final answer here.
N
N
S
9. (2) For the resonance hybrid of question 8, which elements have at least one atom that has a δ + charge? Circle
all that apply:
Carbon Nitrogen Sulfur Hydrogen None of these
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Chemistry 14C Lecture 1 Spring 2013 Exam 1 Page 3
10. (14) In a (fictitious) drug metabolism study, it was discovered that in the body levamisole is in equilibrium with
molecule D:
N
K eq = ?
N
N
S
N
S
Levamisole
Molecule D
Let's see if we can predict the position of this equilibrium. The following questions will guide us. Write a
number in each blank, or circle 'yes' or 'no', as appropriate.
(a) Molecule D has _________ atoms with p orbitals.
(b) Do all the atoms which host these p orbitals lie in the same plane? Yes
No
(c) Does molecule D have a closed loop of p orbitals? Yes
No
(d) Molecule D has ________ pi electrons.
(e) Does molecule D obey Hückel's rule? Yes
No
(f) Is molecule D aromatic? Yes
No
(g) So what do we conclude about K eq ? Circle one:
(i) The equilibrium favors levamisole (K eq < 1)
(ii) The equilibrium does not strongly favor either side (K eq ~ 1)
(iii) The equilibrium favors molecule D (K eq > 1)
11. (4) Levamisole is pale yellow. Molecule D is not the exact same color as levamisole.
(a) Circle the molecule with the smallest HOMO-LUMO gap:
Levamisole Molecule D About equal No way to determine or approximate from given information
(b) Circle the best guess for the color of molecule D:
Colorless Also yellow, but a darker shade than levamisole Orange
Reaction of levamisole with HCl produces a hydrochloride salt, marketed under the trade name of Ergamisol, an
immunomodulator and treatment for parasites. Cation E and cation F are not produced in this process.
N
H
N
Ph
HCl
N
N S Ph
N S
N
H
N S
Levamisol Ergamisol Cation E Cation F
12. (2) What is the relationship between Ergamisol and cation E? Circle all that apply:
Constitutional isomers Conformational isomers Configurational isomers Stereoisomers
Enantiomers Diastereomers Meso compounds None of these
N
S
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Chemistry 14C Lecture 1 Spring 2013 Exam 1 Page 4
13. (5) Let's figure out why reaction of levamisole with HCl forms Ergamisol, and not cation E or cation F. In each
case below, circle one or more reasons that explain why Ergamisol is formed instead of the cation listed.
(a) Ergomisol is formed instead of cation E due to changes in (circle one or more):
Resonance Conjugation Aromaticity Stereochemistry Color Formal charge Strain
(b) Ergomisol is formed instead of cation F due to changes in (circle one or more):
Resonance Conjugation Aromaticity Stereochemistry Color Formal charge Strain
Reaction of D-glucose with NaBH 4 produces sorbitol, used as a substitute for sucrose (table sugar). Sorbitol is also
found in apples, pears, peaches, and prunes. When metabolized, sorbitol is first converted into fructose.
D-glucose
NaBH 4
H 2 O HO
OH OH Question 15 OH Metabolism Fructose
OH
OH
Sorbitol
14. (3) Circle all of ways in which correctly complete this statement: The structures of sorbitol and sucrose differ in
the presence or absence of...
...an acetal ...an anomeric carbon ...at least four stereocenters ...a pyranose None of these are correct
15. (5) Metabolism converts sorbitol into fructose (a ketohexose) by changing the alcohol stereocenter indicated
above into a carbonyl group. No other changes occur. Using this information, complete this drawing of fructose.
C
O
C
C
C
C
16. (2) The fructose produced by enzymatic oxidation of sorbitol is (circle one):
D-fructose L-fructose Neither of these Cannot determine from the given information
17. (4) Draw β-D-glucopyranose. Neatness counts!
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