Name_______________________________ 215 F10-Final Exam Page 2 I. (42 points) (1) (16 points) The titration curve for L-lysine is shown below. Provide (i) the main structures in equilibrium at each of points A and B indicated below and (ii) the structure at the isoelectric point. Draw the structures using the Fischer projections.
6 6 4
Structures in equilibrium at point A: Structures in equilibrium at point B: Structure at the isoelectric point:
(ii)(i)
(2) (16 points) Draw the full structure (including stereochemistry) for the tri-peptide Tyr-Phe-Arg (all L amino acids) in the predominant form it would exist at its isoelectric point. Use the Fischer projections.
Structure at the isoelectric point: The predominant form of this tripeptide at pH 1has a net charge of: (circle one)
+2 +1 0 -1 -24
The predominant form of this tripeptide at pH 11has a net charge of: (circle one)
+2 +1 0 -1 -248
(3) (10 points) Complete the following reaction sequence by providing in each of the boxes the structure of the product [J. Org. Chem. 2010, 75, 3027].
ON
O Ph
OO
NO
HO
O O
1. 4M aq HCl
2. N(CH2CH3)3
5
DCC
5
+ CO2 +HN
HN
O
+
Name_______________________________ 215 F10-Final Exam Page 3 II. (42 points) (1) (16 points) Treatment of enone A with NaOH/H2O results in the formation of cyclohexanone (C) and acetone (D) via β-hydroxy ketone intermediate B. Provide in the box below a step-by-step mechanism using the curved arrow convention for the following transformation. You do not need to show Na+ for each step.
O O
OH
O O+
NaOH/H2O NaOH/H2O
Mechanism for B -> C and D:
A B C D
106
OA
Mechanism for A -> B:
O
OB HOH
OH
Na
Na
O
OH
B O
O
C
D
(2) (26 points) Provide in the box below a step-by-step mechanism using the curved arrow convention for the following transformation. You do not need to show Na+ for each step.
NaOCH2CH3HOCH2CH3
Mechanism:
OCH2CH3Na
Na
+ enantiomer
26O OCH2CH3
O
Na O OCH2CH3
OCH3CH2O
O
O
CH3CH2O
O
O
Name_______________________________ 215 F10-Final Exam Page 4
III. (56 points) Provide in the boxes below a step-by-step mechanism using the curved arrow convention for each of the following transformations. You may use H-A as your Brønsted acid and A- as its conjugate base.
HN N
H
O
O
OH
NO2O2N
HN OH
O
NO2O2N
H NO
OHH H
Cl+
HCl/H2O
HN N
H
O
O
OH
NO2O2N
H A
HN OH
O
NO2O2N
HN
O
OHHH
Cl26
(1) (26 points)
Mechanism:
(2) (30 points) [Org. Lett. 2010, 12, 904]
HO OHOH
OCH3
OCH3
HO OO
+ 2 CH3OHTsOH (catalytic)
30
Mechanism:
HO OHOH
OCH3
OCH3
H A
HO OO
Name_______________________________ 215 F10-Exam Exam Page 5 IV. (38 points) Shown below is a trisaccharide recently isolated from Securidaca welwitschii [Helv. Chim. Acta 2010, 93, 2237]. Answer the following questions about this trisaccharide, 1.
1
(1) (4 points) Label each of the glycosidic bonds in trisaccharide 1 using a small arrow ( → ).
(2) (4 points) Classify each glycosidic linkage in 1 as α or β right next to each of the arrows you have shown.
(3) (3 points) How many D-sugar units does trisaccharide 1 have? (circle one) 0 1 2 3
(4) (3 points) Is the hemi-acetal OH in trisaccharide 1 α or β? (circle one) α β
(5) (3 points) Is trisaccharide 1 a reducing sugar? (circle one) Yes No
(6) (4 points) Describe the linkages between the following sugar units [e.g., α(1 -> 6)]:
For A and B: For B and C:
A
BC
O
O
OHO
HO
OH
OHHO
OHO
OH
HO O
(7) (17 points) Draw Fischer projections for the open-chain forms of the three carbohydrates produced when trisaccharide 1 is hydrolyzed with a warm dilute aqueous acidic solution.
566
Carbohydrate A Carbohydrate B Carbohydrate C
Name_______________________________ 215 F10-Final Exam Page 6
V. (32 points) Complete the following reactions by providing in each of the boxes the structure of the reagent, intermediate, or product. Indicate stereochemistry for the product/intermediate and if more than one stereoisomer is formed, draw one structure and write “+ enantiomer” or “+ diastereomer.”
OO OO
O
Ph
Ph
Ph
OO
O
O OPhO
Ph
HO
OH
HOO OCH3
TsOH (catalytic)
5
+ CH3OH
5
5 5
(1) [Synthesis 2010, 3004]
(2)
HBr(gas)CH2Cl2
(solvent)
NH2
(1 equiv)
K2CO3
SN2
Ph OCH3
O NaOCH3(catalytic)
CH3OH(sovent)
4 x+
(3) [Org. Lett. 2010, 12, 904]
H
H
O HOK
Cl
OCH3
α-anomer
4
+ KCl
(4) [J. Am. Chem. Soc. 2010, 132, 14064]
OCH2CH3
HO O LDA (2 equiv)
THF, -78 °C
dilithium dianion
1. CH3I (1 equiv)
SiCl2.
4 4+ LiI + LiCl
Name_______________________________ 215 F10-Final Exam Page 7 VI. (30 points) Complete the following reactions by providing in each of the boxes the structure of the product or intermediate. Indicate stereochemistry for the product/intermediate and if more than one stereoisomer is formed, draw one structure and write “+ enantiomer” or “+ diastereomer.”
5
(1) [Synlett 2010, 3011]
(2)
OCH2CH3
ON
O
O
K2CO3
O
OCH2CH3
O5
CH3CH2NH2(excess)
heat+ H2O + CH3CH2OH
(3)
O H
OOH
5
CC LiH3C1.
2. aq NH4Cl (protonation)
5
PCC
(4)
CH3
CH3OOCH3
CH3OO
H
Br
O
+NaOHCH3OH
5
+ H2O
(5)
OCH2CH3
OLi OLiO O
Br
(1 equiv)1.
2. aq NH4Cl (protonation)
5
+ LiBr
+ Li+
Page 10 The Reagent List Shown below is a list of key reagents (not always the whole recipe) that may be useful for solving questions on the final exam. reagent classification or specialized use ____________________________________________________________________________________ From OsO4 oxidation Chem 210 KMnO4 oxidation peroxyacid epoxidation (e.g., 3- or meta-chloroperoxybenzoic acid) i. O3; ii. (CH3)2S or Zn ozonolysis i. O3; ii. H2O2 ozonolysis NaNH2 base, nucleophile NaH base KOC(CH3)3 bulky base H2/Pd hydrogenation H2/Pd, BaSO4, quinoline hydrogenation i. BH3 or 9-BBN; ii. H2O2, NaOH hydroboration PBr3 e.g., R-OH → R-Br SOCl2 e.g., R-OH → R-Cl
p-CH3C6H4SO2Cl (p-TsCl) tosylate formation CH3SO2Cl (MsCl) mesylate formation N-bromosuccinimide (NBS)
N
O
O
Br
source of electrophilic Br =========================================================================== Ch. 13 C5H5NH+•ClCrO3- (PCC) oxidant CrO3/H2SO4/H2O/acetone oxidant i. ClC(=O)-C(=O)Cl, (CH3)2SO; ii. N(CH2CH3)3 oxidant Ch. 14 NaBH4 nucleophilic hydride LiAlH4 nucleophilic hydride diisobutylaluminum hydride (DIBAL) nucleophilic hydride RMgX nucleophilic carbon RLi nucelophilic carbon 4-CH3C6H4SO3H (p-TsOH) (pKa ~ -1) organic-soluble acid Raney Ni desulfurization HSCH2CH2SH; HSCH3 thioacetal/thioketal formation BF3•O(CH2CH3)2 Lewis acid H2NNH2 hydrazone formation H2NOH oxime formation
Page 11 Ch. 15 SOCl2 R-C(=O)OH → R-C(=O)Cl Ag2O, NaOH, H2O2 oxidant -CH2
+N2 (diazomethane) e.g., R-C(=O)OH → R-C(=O)OCH3 Ch. 17 LiN[CH(CH3)2] (LDA) bulky base K2CO3 weak base Amino acids & proteins C6H11N=C=NC6H11 RC(=O)OH activation (DCC; dicyclohexylcarbodiimide) PhCH2OC(=O)Cl (benzyl chloroformate) N-protection ROC(=O)N3 (R = tert-butyl) N-protection [tert-butyl-O-C(=O)-]2O (Boc2O) N-protection
H3C C O O O CCH3
H3CH3C O O CH3
CH3
(9-fluoromethyl)methoxycarbonyl chloride N-protection (Fmoc)
CH2
OCl
O
Cl3CC(=O)OH O-deprotection H2, Pd/C catalytic hydrogenolysis Sanger’s reagent N-terminus AA determination
NO2
FO2N
The 20 naturally occurring amino acids Page 12
H2N OHH CH3
O
H2N OHH
O
H2N OHH H
O
ONH2
H2N OHH
O
H2N OHH
O
SH
O NH2
H2N OHH
O
H
H2N OHH
O
H2N OHH
O
SCH3
HN
OH
O
H
H2N OHH
O
OH
H2N OHH
O
HHO
H2N OHH
O
NH
H2N OHH
O
OH
H2N OHH
O
H2N OHH
O
Alanine
Asparagine
Cysteine
Glutamine
Glycine
Isoleucine
Leucine
Methionine
Phenylalanine
Proline
Serine
Threonine
Tryptophan
Tyrosine
Valine
Acidic amino acids
Basic amino acids
Neutral amino acids
H2N OHH
O
OOH
Aspartic acid
H2N OHH
O
O OHGlutamic acid
H2N OHH
O
NHArginine
H2N OHH
O
Histidine
H2N OHH
O
Lysine
NH2
NH
NH2
HN N
pKa Values for the Ionizable Functional Groups of an α-Amino Acid Amino acid α-C(=O)OH α-NH3
+ side chain ___________________________________________________________________________________________________ Alanine 2.35 9.87 - Arginine 2.01 9.04 12.48 Asparagine 2.02 8.80 - Aspartic acid 2.10 9.82 3.86 Cysteine 2.05 10.25 8.00 Glutamic acid 2.10 9.47 4.07 Glutamine 2.17 9.13 - Glycine 2.35 9.78 - Histidine 1.77 9.18 6.10 Isoleucine 2.32 9.76 - Leucine 2.33 9.74 - Lysine 2.18 8.95 10.53 Methionine 2.28 9.21 - Phenylalanine 2.58 9.24 - Proline 2.00 10.60 - Serine 2.21 9.15 - Threonine 2.09 9.10 - Tryprophan 2.38 9.39 - Tyrosine 2.20 9.11 10.07 Valine 2.29 9.72 - ________________________________________________________________