-1-
1.
Draw structures for the products you would expect to obtain from reaction of β-Dgalactopyranose (A) with each of the reagents below. Be sure to include all relevant
stereochemistry. (40 pts).
OH
HO
O
HO
OH
O
H
β-D-galactopyranose (A)
CH3I
a)
A
Ag2O
OMe
MeO
O
MeO
OMe
O
Me
HNO3
b)
A
∆
(CH3CO)2O
c)
H
HO
HO
H
A
pyridine
CO2H
OH
H
H
OH
CO2H
OAc
AcO
O
AcO
OAc
O
Ac
NaBH4
d)
H
HO
HO
H
A
H 2O
OH
MeOH
e)
HO
A
dry HCl
CH2OH
OH
H
H
OH
CH2OH
O
HO
O
H
OMe
-2-
H
H
HO
HO
H
1) HCN
f)
A
2) DIBAH
3) H3O+
CHO
OH
OH
H
H
OH
CH2OH
Br2
g)
A
H 2O
A
2) (CH3CO)2O
3) NaOMe
i)
A
H
HO
HO
H
CO2H
OH
H
H
OH
CH2OH
CHO
H
OH
H
H
OH
CH2OH
CHO
HO
H
HO
H
H
OH
CH2OH
H2NOH
h)
+
HO
H
HO
HO
H
red P / ∆
HI
(n-hexane)
2.
The octapeptide saralasin is a specific antagonist of agniotensin II. A derivative of
saralasin is used therapeutically as an antihypertensive. Amino acid analysis of saralasin shows
the presence of the following amino acids : Ala, Arg, His, Pro, Sar, Tyr, 2 Val.
Briefly describe a plausible technique for analyzing the amino acid content of saralasin.
Two-three sentences plus a diagram will suffice. (10 pts).
a)
3
2
absorbance
Rigorous hydrolysis of a protein with aqueous HCl
will cleave all peptide bonds to liberate the
component amino acids. Analyze the amino acids
by chromatography, where the retention time is
characteristic of each AA, and the absorbance of a
suitable derivative is proportional to molar quantity.
2
2
2
1
retention time
1
-3-
N-terminal analysis by the Edman method shows that saralasin contains sarcosine (N-methyl
aminoethanoic acid) at the N-terminus (see below). Provide structures for C and D, and a
detailed mechanism for this cleavage. (15 pts).
b)
B
H
Me
1) Ph-N=C=S / H+ / ∆
O
N
N
peptide
CO2H
H
Ph
N
C
C
2) H3O+
+
D
S
H
nucleophilic
addition
B
H
N
Ph
S
Me
H
H+ catalyzed
O
N
N
peptide
CO2H
Ph
cyclization
H
N
Me
S
O
N
peptide
N
H
CO2H
H
H
N
Me
S
N
+
(peptide)
Ph
B
NH2
O
H catalyzed
cleavage
CO2H
Ph
H
N
Me
S
O
N
peptide
N
H
CO2H
H
C
H+ catalyzed
Ph
S
rearrangement
Me
N
N
O
D
c) Partial hydrolysis of saralasin with dilute HCl yields the following fragments: Tyr-Val-His,
Sar-Arg-Val, His-Pro-Ala, Val-Tyr-Val, Arg-Val-Tyr. What is the structure of saralasin?
(10 pts).
Sar-Arg-Val
The Complete Sequence is:
Arg-Val-Tyr
Sar-Arg-Val-Tyr-Val-His-Pro-Ala
Val-Tyr-Val
Tyr-Val-His
His-Pro-Ala
-4Propose a solid state synthesis of the fragment Tyr-Val-His beginning with polymer P (see
below), and utilizing any protected derivatives of Try, Val and His of your chosing. Show all
reagents and steps clearly. (15 pts).
d)
CO2H
P
CH2Cl
NH2
HO
NH2
N
H
NH2
Val
Tyr
CO2H
N
CO2H
His
O
C
N
O-
NHBOC
N
H
O
O
C
C
N
O
TFA
P
H2C
N
NHBOC
N
H
CO2H
O
H2 C
NHBOC
P
NH2
N
H
DCC
CO2H
BOC
N
H
H
O
N
C
O
TFA
P
H2C
H2N
O
H
O
N
C
NHBOC
HO
O
H2C
P
DCC
O
N
N
N
H
N
H
O
N
HN
H
BOC
HO
H
O
N
C
1) TFA
O
H2C
Tyr-Val-His
P
2) H2 / Pd
O
N
N
H
3.
For each reaction given below, provide either the missing reagents or products (in the
boxes). Show any intermediates in the space provided. For multistep syntheses, be sure to list
the reagents in the order they are utilized (none require more than 3 steps). (40 pts).
Et-CH
CH-CO2Me
NaOMe
a)
+
O
MeO2C-CH2 C CH3
MeOH
Et-CH CH2-CO2Me
MeO2C-CH C CH3
O
H3O+
Et-CH CH2-CO2H
∆
CH2 C CH3
O
-5Cl
1) NH3
b)
NO2
c)
CH3
C
NH2
2) Br2 / HO-
O
NH2
3) H2 / Pd
CH CH2 CH
CH-CO2Me
1.0 eq HBr
Br
CH3 C CH2 CH2
CH3 HC CH-CO2Me
CH3
1) RCO3H
O
2) MeO -
d)
O
3) Ac2O
Me
Et
e)
1) 1 equiv
LDA
OMe
Me
Me
Et
O
2) MeI
O
1) HO-
f)
OHC-(CH2)5-CHO
2) H2 NEt / H2 / Pd
Cl
NMe2
3) excess MeCl
Et
-6excess
CH3NH2
g)
Me
∆
CH2
Br
OH
1) KMnO4 / ∆
2) ∆ (-H2O)
h)
O
OMe
3) MeOH
O
4.
Provide a detailed mechanistic rationale for the transformation shown below. (15 pts).
OMe
O18
H2O18
MeO
MeO
MeO
+
H
H
+
+
H
-H
H
H
OMe
OMe
MeO
MeO
MeO
H
MeO
O
H
H
-MeOH
18
H2O
P.T.
-MeOH
H
OMe
OMe
MeO
18
H2O
MeO
H
O
O18
-75.
If the DNA sequence -TAA-CCG-GAT- were incorrectly copied during replication and
became -TGA-CCG-GAT-, what effect would there be on the sequence of the protein produced
during translation (use the data from the table below). (15 pts).
Codon Assignments
1st base (5’ end)
2nd base
U
___________Third base (3’ end)___________
C
A
G
U
U
C
A
G
Phe
Ser
Tyr
Cys
Phe
Ser
Tyr
Cys
Leu
Ser
Stop
Stop
Leu
Ser
Stop
Trp
C
U
C
A
G
Leu
Pro
His
Arg
Leu
Pro
His
Arg
Leu
Pro
Gln
Arg
Leu
Pro
Gln
Arg
A
U
C
A
G
Ile
Thr
Asn
Ser
Ile
Thr
Asn
Ser
Ile
Thr
Lys
Arg
Met
Thr
Lys
Arg
G
U
C
A
G
Val
Ala
Asp
Gly
Val
Ala
Asp
Gly
Val
Ala
Glu
Gly
Val
Ala
Glu
Gly
replication
DNA :
-TAA-CCG-GAT-
-TGA-CCG-GAT(error)
transcription
transcription
-AUU-GGC-CUA-
mRNA :
-ACU-GGC-CUA-
translation
Protein
fragment :
translation
-Ile-Gly-Leu-
-Thr-Gly-Leu-
6.
Shown below are the structures of adenine (A), guanine (G), thymine (T) and cytosine
(C). Please show the hydrogen bonds between the appropriate base pairs (this will require
accurate drawings. (10 pts).
NH2
O
N
N
N
HN
N
H
N
O
H2N
N
H
N
A
Me
HN
O
H
O
N
H
N
O
T
H
N
N
Me
N
NH
O
H
H
N
N
H
N
H
O
N
NH
N
O
A
H
T
N
H
C
HN
HN
N
N
H
G
N
NH2
G
C