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 - ________________________________________________________________