1- Why

is a 1,3-cis disubstituted cyclohexane more stable than its trans isomer?

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2- fluoxetine is an extraordinarily effective antidepressant but has no activity against
migraine. The enantiomer shown below, however, works remarkably well in
preventing migraine. Assign an R/S configuration to the enantiomer below.

37 It
I

s
4 E

Goingcounterclockwise w 4 as a dash S
3- Ibuprofen has one chiral center and is sold commercially under the trade names as Advil,
Nuprin, and Motrin as a 50:50 mixture of R and S. It turns out, however, that only one of
its enantiomers (shown below) is active as an analgesic and anti-inflammatory agent.
Assign an R/S configuration to the enantiomer below.

e't
3 4

Is
qq.lt

clockwise w 4 as wedge R g S
 As an
example take methyl groups
as substituents
nor
proa pear

cis
is
2
2
2 Trans
3 3
terror
s

Z t
z 3
f
f
both substituents
f f substituent
equitorial

are one is

equatorial stable To axial less stable n

 4-

2 s
z
No
yes
2

yes I
yes

we look at the
from
molecules helicopter
5-
the top view
a
i
c c

go
111111

111
Br B
Cig 1,2 dimethyl
cyclopentane
cis L bromo 3 methylcyclebutane
 6-

Axial

Skip
7- Draw the structure of a meso compound that has five carbons and three
chirality centers.

This

turned out to be
question

I expected
harder than what
way

 8-

The antimalarial drug erythro-mefloquine (Lariam) is shown below. This drug is sold as a
racemic mixture of (+) and (-) compounds. It is believed that (+)-erythro-mefloquine is
responsible for anti-malaria properties, while (-)-erythro-mefloquine is responsible for the side
effect of psychosis. Positions 11 and 12 are numbered in the structure below.

11 gp3
se sp
A z s
se se se
set set
set Sf
sp2 12

SEZ q2 Sflsp2 sp2

Sp3
Sf

A) Label all carbon and nitrogen atoms as sp, !"! , !"" hybridized in the structure above

B) In 2012, scientists determined that (+)-erythro-mefloquine is the (11S, 12R) stereoisomer.

Note that positions 11 and 12 are indicated in the above structure. Draw this isomer,
clearly indicating stereochemistry.

Next page
C) Draw the structure of the enantiomer of (+)-erythro-mefloquine.

Next page
 B
I
N
a is
g4
as a dash

clockwise w 4 as a wedge R Ai S

N CF
CFz

C 3

Ho
HN
H clockwise w 4 as a wedge R S

clockwise w 4 as a dash aR

N CF
CFz
D ee
Observed 9 too
a d pure enantiomer

6 too 33.33
180
d The t enantiomer

sample is Loo

this means that 100 33 33

33.33
66 67 is a racemic
t enantiomer
mixture of Ct C
enantiomers

as
a.ie ia3n7i
mere3 m

ee c

percentage of G enantiomer 33
 Observed rotation
D) A scientist at Pfizer decides to try synthesizing only (+)-erythro-mefloquine. The sample
of erythro-mefloquine that they make has a specific rotation of +60. If the specific
rotation of pure (+)-erythro-mefloquine is +180, what is the enantiomeric excess (%ee) of
the sample? What are the percentages of (+)-erythro-mefloquine and (-)-erythro-
mefloquine? Show your work.

9-

Next ease
steps
1 check for chiral centers
10- 2 check for planes me d symmetry
plane dsymmetryexists so a chiral molecule
ne of symmetry or inversioncenter chiral malecul

a carbon atom connected to 4

different groups chiral And no
plane of
f carbon atom connected to 4 different groups chiral symmetry
atoms not mess
c carbon connected to 4 different groups chira
9 we want most substituents to
be equitorial

as 6
3 z I equito rial down

Ho
Ho
4 6 OH
5 OH
z
HO 3

OH
Best we can do is to have 5 hydroxyl
substituents as equitarial 1 axial
 11-

Differentenantiomers Same enantiomer

z f

ma 4 clockwise 4astash R 3Bothcases counterclockwise 44 asta

3 3 2 Start
4 R ss 44IFIEky.in
4,5J I
look down the
Same enantiomer C H bant
sameenantiomer counterclockwise w 4astash
It
Bothcases effn4astash s
12-
Hz
counterclockwise w
4 asada
s
4

l I i R
a2
413.3 3.5 4 I R
u 2
4

o c
o c
ch
7 1 23
4
H
clockwis w 4 as wedge Refligg
R
R R
as
7
13-

R S

4 I
9
Gs
14- i 4 by
Ft

R R R

I 4

4
c
I
R
34
4

r
15-

Es l

4 0
I Ht

3 z

1 4