proteins- david klein Flashcards
1
Q
Structure of α-Amino Acids
A
An amino acid contains two key functional groups:
Amino group (–NH₂)
Carboxylic acid group (–COOH)
These two groups can be separated by various numbers of carbon atoms, but the most biologically important amino acids are those where:
The amino group is attached to the α-carbon, which is the carbon adjacent to the carboxyl group.
➤ α-Amino Acids:
Defined by the structure:
H
2
N
–
C
H
(
R
)
–
C
O
O
H
H
2
N–CH(R)–COOH
The α-carbon:
Is bonded to:
An amino group (–NH₂)
A hydrogen (H)
A carboxyl group (–COOH)
A side chain group (R)
Becomes a chiral center if R ≠ H.
2
Q
Peptide Bonds (Amide Linkages)
A
Amino acids join to form peptides or proteins through amide bonds called peptide bonds.
This occurs via a condensation reaction:
The –NH₂ group of one amino acid reacts with the –COOH group of another.
A molecule of water (H₂O) is eliminated.
A peptide bond is formed:
–
C
O
–
N
H
–
–CO–NH–
This reaction links amino acids into long chains (polypeptides).
3
Q
Peptides
A
A peptide is a short chain of amino acids linked by peptide bonds (amide linkages).
Naming is based on the number of amino acids:
Dipeptide: 2 amino acids
Tripeptide: 3 amino acids
Tetrapeptide: 4 amino acids
And so on…
4
Q
Polypeptides vs. Proteins
When the chain grows longer:
A
Chains with fewer than 40–50 amino acids are typically called polypeptides.
Chains with more than 50 amino acids are usually considered proteins.
5
Q
Proteins and Their Roles
Proteins are biologically essential macromolecules.
A
They perform a variety of structural, regulatory, transport, and catalytic functions.
Enzymes are a class of proteins that:
Act as biological catalysts
Speed up chemical reactions in cells
Are crucial for metabolism and life processes
🧠 It is estimated that the human body uses more than 50,000 enzymes to carry out life functions efficiently.
6
Q
What is a peptide?
A
A: A short chain of amino acids linked by peptide (amide) bonds.
7
Q
How many amino acids make up a dipeptide?
A
A: 2
8
Q
How many amino acids make up a tripeptide?
A
A: 3
9
Q
What kind of bond joins amino acids in peptides?
A
A: A peptide bond (–CO–NH–)
10
Q
What is the difference between a polypeptide and a protein?
A
A: A polypeptide has fewer than 40–50 amino acids, while a protein is a longer chain (usually >50 amino acids).
11
Q
What are enzymes?
A
A: Proteins that function as biological catalysts to speed up chemical reactions in cells.
12
Q
At what point is a peptide typically considered a protein?
A
A: When it has more than 50 amino acids.
13
Q
How many enzymes are estimated
A
to be needed by the human body?
A: Over 50,000
14
Q
What are some functions of proteins in the body?
A
A: Catalysis (enzymes), structure (e.g., collagen), transport (e.g., hemoglobin), signaling (e.g., hormones).
15
Q
Not All Amino Acids Are in Proteins
A
While 20 standard amino acids are commonly found in proteins, other amino acids exist in the body that:
Are biologically important
Do not get incorporated into proteins
Serve specific physiological roles
16
Q
GABA (γ-Aminobutyric Acid)
A
Structure: NH₂–CH₂–CH₂–CH₂–COOH
Classification: γ-amino acid (amino group is on the γ-carbon—3 carbons away from the carboxyl group)
Function:
Acts as a neurotransmitter
Found in the brain
Inhibitory — reduces neuronal excitability
Not used in proteins
17
Q
Thyroxine
A
Structure: A complex derivative of tyrosine with iodine atoms
Classification: A modified amino acid
Function:
A hormone secreted by the thyroid gland
Regulates metabolism, growth, and development
Not incorporated into proteins directly
18
Q
Are all amino acids found in proteins?
A
A
A: No, some amino acids (like GABA and thyroxine) are not found in proteins but still serve important functions in the body.
19
Q
What does GABA stand for?
A
A: γ-Aminobutyric acid
20
Q
What is the role of GABA in the body?
A
A: It acts as an inhibitory neurotransmitter in the brain.
21
Q
Why is GABA classified as a γ-amino acid?
A
A: Because the amino group is on the γ-carbon (3 carbons away from the carboxyl group).
22
Q
Is GABA incorporated into proteins?
A
A: No
23
Q
What is thyroxine?
A
A: A hormone derived from tyrosine, produced by the thyroid gland.
24
Q
What is the biological role of thyroxine?
A
A: It regulates metabolism, growth, and development.
25
Is thyroxine a standard amino acid?
A: No, it is a modified amino acid, not found in proteins.
26
Essential vs. Non-Essential Amino Acids
Total amino acids in proteins: 20 standard L-amino acids.
The human body can synthesize 10 of them. These are called non-essential amino acids because they don’t need to come from the diet.
The other 10 must be obtained from food and are called essential amino acids.
27
Essential Amino Acids:
Isoleucine
Leucine
Methionine
Phenylalanine
Threonine
Tryptophan
Valine
Arginine (conditionally essential)
Histidine
Lysine
28
Complete vs. Incomplete Proteins
Complete proteins contain all 10 essential amino acids.
Sources: Meat, fish, milk, eggs
Incomplete proteins are deficient in one or more essential amino acids.
Examples:
Rice: low in lysine and threonine
Corn: low in lysine and tryptophan
Beans & peas: low in methionine
29
Nutritional Considerations
Meat eaters get all essential amino acids from animal products.
Vegetarians can meet amino acid needs through milk and eggs.
Vegans, who consume no animal products, must carefully combine plant sources (like rice + beans) to obtain a full set of amino acids.
30
Deficiency Risk
Inadequate intake of essential amino acids can cause diseases, impair growth, and reduce protein synthesis.
Proper diet planning is critical for vegetarians and especially vegans.
31
What are essential amino acids?
A: Amino acids the body cannot synthesize and must be obtained from the diet.
32
How many amino acids are essential for humans?
A: 10, including arginine which is conditionally essential.
33
What are non-essential amino acids?
A: Amino acids the body can synthesize on its own.
34
What is a complete protein?
A: A protein source that contains all 10 essential amino acids.
35
Give examples of complete protein sources.
A: Meat, fish, milk, eggs.
36
What is an incomplete protein?
A: A protein source lacking one or more essential amino acids.
37
What essential amino acids is rice low in?
A: Lysine and threonine
38
What essential amino acids is corn low in?
A: Lysine and tryptophan
39
What is missing in beans and peas?
A: Methionine
40
How can vegetarians meet their amino acid needs?
A: Through milk and eggs (complete animal-derived proteins).
41
What must vegans do to get all essential amino acids?
A: Combine complementary plant proteins, like rice and beans.
42
What happens with inadequate intake of essential amino acids?
A: It can lead to diseases and impaired protein function and growth.
43
pH 1 Condition – Fully Protonated Form
At very low pH (around 1), the solution is highly acidic.
The amino acid exists in a fully protonated form:
The carboxyl group (–COOH) is protonated.
The amino group (–NH₃⁺) is also protonated (as an ammonium ion).
The molecule carries a net positive charge due to the –NH₃⁺ group.
44
Deprotonation and pKa Values
Each ionizable proton has its own pKa value — a measure of how easily it donates a proton.
🔹 pKa₁ (Carboxylic acid group)
–COOH → –COO⁻ + H⁺
Typically around 2
This is deprotonated first as the pH rises.
🔹 pKa₂ (Amino group)
–NH₃⁺ → –NH₂ + H⁺
Typically around 9–10
This deprotonates after the carboxyl group.
45
Additional pKa Values
Some amino acids have acidic or basic side chains (like aspartic acid, lysine, histidine).
These side chains can also ionize, contributing a third pKa.
46
Important Notes
Order of deprotonation:
Carboxylic acid group (more acidic)
Ammonium group (less acidic)
(If present) Ionizable side chain
This behavior governs:
The zwitterion form
Isoelectric point (pI)
Charge at different pH values
47
What is pKa?
A: It is the pH at which 50% of a functional group is deprotonated.
48
What happens to an amino acid at very low pH (~1)?
A: Both –COOH and –NH₃⁺ groups are fully protonated; the molecule has a positive charge.
49
What is pKa₁ in amino acids?
A: The pKa of the carboxyl group, usually around 2.
50
What is pKa₂ in amino acids?
A: The pKa of the ammonium group (–NH₃⁺), usually around 9–10.
51
Which functional group deprotonates first as pH increases?
A: The carboxylic acid group (–COOH).
52
At what pH does the amino group typically deprotonate?
A: Around pH 9–10
53
Do all amino acids have only two pKa values?
A: No — amino acids with acidic or basic side chains have a third pKa.
54
Give an example of an amino acid with three pKa values.
A: Aspartic acid (acidic side chain), lysine (basic side chain)
55
What charge does the amino acid carry after losing only its carboxylic proton?
A: Neutral (zwitterion) — COO⁻ and NH₃⁺ are both present.
56
What is the net charge after both groups are deprotonated?
A: Negative (–1) — COO⁻ and NH₂
57
Understanding pKa and Charge States of Amino Acids
🔹 Carboxylic Acid Group (–COOH)
Typical pKa₁ range: ~2–3
For example, alanine has pKa₁ = 2.34.
At pH = pKa (e.g., 2.34):
50% of the group is in the uncharged form –COOH
50% is in the anionic form –COO⁻
At pH < 2.34 (acidic): The group stays protonated (–COOH)
At pH > 2.34: The group loses H⁺ → becomes –COO⁻
✅ At physiological pH (~7.4), the carboxylic acid is deprotonated (–COO⁻)
58
Understanding pKa and Charge States of Amino Acids
Ammonium Group (–NH₃⁺)
Typical pKa₂ range: ~9–10
Alanine: pKa₂ = 9.69
At pH = 9.69:
50% exists as –NH₂ (uncharged)
50% as –NH₃⁺ (charged)
At pH < 9.69: The group is protonated as –NH₃⁺
At pH > 9.69: The group loses H⁺ and becomes –NH₂
✅ At physiological pH, the group is protonated (–NH₃⁺)
59
What is the typical pKa of the –COOH group in amino acids?
A: Around 2–3
60
At what pH is –COOH 50% deprotonated and 50% protonated?
A: At its pKa, e.g., 2.34 for alanine
61
What form of the carboxyl group predominates at physiological pH (~7.4)?
A: Deprotonated form (–COO⁻)
62
What form dominates at pH below the pKa?
A: The protonated form (–COOH)
63
What is the typical pKa of the –NH₃⁺ group?
A: Around 9–10 (e.g., 9.69 for alanine)
64
At what pH does –NH₃⁺ exist 50/50 with –NH₂?
A: At its pKa, e.g., 9.69
65
What form of the amino group predominates at physiological pH?
A: Protonated form (–NH₃⁺)
66
What happens to the amino group above its pKa?
A: It deprotonates to form –NH₂
67
What is the overall charge of an amino acid at physiological pH?
A: 0 — exists as a zwitterion with both +1 (NH₃⁺) and –1 (COO⁻)
68
Which group is deprotonated first as pH rises?
A: The carboxyl group (–COOH)
69
🌟 Zwitterion Form of Amino Acids
A zwitterion is a molecule that contains both positive and negative charges, yet is electrically neutral overall.
For amino acids at physiological pH (~7.4):
The carboxyl group is deprotonated → –COO⁻
The amino group is protonated → –NH₃⁺
Thus, the amino acid:
Has internal charge separation (like a salt)
Is referred to as a zwitterionic species
69
Physical Properties of Zwitterions
Due to charge separation, amino acids:
Are highly soluble in water
Exhibit salt-like properties
Have high melting points
70
Amphoteric Nature of Amino Acids
Amino acids are amphoteric, meaning they can act as both acids and bases, depending on the environment.
➤ Acting as an Acid (Reaction with a Base):
The –NH₃⁺ group donates a proton:
–
𝑁
𝐻
3
+
+
𝑂
𝐻
−
→
–
𝑁
𝐻
2
+
𝐻
2
𝑂
–NH
3
+
+OH
−
→–NH
2
+H
2
O
This occurs in basic conditions
➤ Acting as a Base (Reaction with an Acid):
The –COO⁻ group accepts a proton:
–
𝐶
𝑂
𝑂
−
+
𝐻
3
𝑂
+
→
–
𝐶
𝑂
𝑂
𝐻
+
𝐻
2
𝑂
–COO
−
+H
3
O
+
→–COOH+H
2
O
This occurs in acidic conditions
71
What is a zwitterion?
A: A molecule with both a positive and negative charge, but an overall neutral charge.
72
What groups are ionized in a zwitterionic amino acid?
A: –NH₃⁺ (amino group) and –COO⁻ (carboxyl group)
73
What form do amino acids take at physiological pH?
A: Zwitterionic form
74
Why are amino acids highly water-soluble?
A: Because they exist as ionic zwitterions in water.
75
Why do amino acids have high melting points?
A: Due to internal salt-like interactions in the zwitterionic structure.
76
What does it mean that amino acids are amphoteric?
A: They can act as both acids and bases.
77
What happens when a zwitterion reacts with a base like OH⁻?
A: The –NH₃⁺ group loses a proton → becomes –NH₂
78
What happens when a zwitterion reacts with an acid like H₃O⁺?
A: The –COO⁻ group gains a proton → becomes –COOH
79
What does the zwitterion become when it donates a proton?
A: A conjugate base form (–NH₂)
80
What does the zwitterion become when it accepts a proton?
A: A conjugate acid form (–COOH)
81
What is the Isoelectric Point?
The isoelectric point (pI) is the pH at which an amino acid exists predominantly as a zwitterion — i.e., it has no net charge.
At this point:
The positive and negative charges within the molecule balance each other out.
The amino acid is least soluble in water and will not migrate in an electric field.
82
Amino Acids Without Ionizable Side Chains
For amino acids that lack an acidic or basic side chain (e.g., alanine), the pI is calculated by taking the average of the two main pKa values:
pKa₁: For the carboxylic acid (–COOH)
pKa₂: For the ammonium ion (–NH₃⁺)
✅ Example: Alanine
pKa₁ = 2.34 (–COOH)
pKa₂ = 9.69 (–NH₃⁺)
pI = (2.34 + 9.69)/2 = 6.02
82
Amino Acids With Acidic or Basic Side Chains
For these amino acids, the pI is calculated from the two closest pKa values that flank the neutral zwitterion form:
✅ Example: Lysine (Basic Side Chain)
pKa₁ (α-NH₃⁺) = 8.95
pKa₂ (side chain –NH₃⁺) = 10.53
pI = (8.95 + 10.53)/2 = 9.74
Lysine's zwitterion exists between the two cationic forms, so use the two highest pKa values (both basic)
83
Why is the pI important?
A: At the pI, the amino acid has lowest solubility and no net movement in an electric field.
84
At pH below pI, what is the net charge of the amino acid?
A: Positive
85
At pH above pI, what is the net charge?
A: Negative
86
When is the amino acid least soluble in water?
A: At its isoelectric point (pI)
87
What is Electrophoresis?
Electrophoresis separates amino acids in a mixture based on differences in their isoelectric points (pI).
A sample is applied to a buffered medium (like paper or gel), and an electric field is applied across it.
Amino acids migrate depending on their net charge at the pH of the buffer.
88
Detection of Amino Acids – Ninhydrin Test
Amino acids are colorless, so a detection method is needed.
Ninhydrin is a reagent that reacts with primary amines in amino acids to form a deep purple-colored product.
The reaction releases H₂O, CO₂, and an aldehyde (RCHO) as by-products.
Proline, a secondary amine, reacts differently (gives a yellow product).
The number of purple spots = number of primary amino acids in the mixture.
88
Migration Behavior
General Rule:
pH < pI → Amino acid is positively charged → Migrates toward cathode (–)
pH > pI → Amino acid is negatively charged → Migrates toward anode (+)
pH = pI → Amino acid is neutral (zwitterion) → No migration
89
electrophoresis is for analytical use only
Analytical Use Only
Electrophoresis is ideal for analytical purposes, i.e., detecting how many different amino acids are present.
It’s not suitable for isolating large amounts of amino acids.
For full separation and collection, methods like column chromatography are used.
90
What principle is electrophoresis based on?
A: The difference in pI values of amino acids.
91
What happens when pH = pI?
A: The amino acid is a zwitterion and does not migrate.
92
What is the net charge of an amino acid when pH < pI?
A: Positive — migrates toward the cathode (–)
93
What is the net charge when pH > pI?
A: Negative — migrates toward the anode (+)
94
What happens to lysine (pI = 9.74) at pH 6?
A: It is positively charged and moves to the cathode (–)
95
What happens to glutamic acid (pI = 3.22) at pH 6?
A: It is negatively charged and moves to the anode (+)
96
What happens to alanine (pI = 6.02) at pH 6?
A: It is zwitterionic, so it does not migrate
97
What reagent is used to detect amino acids after electrophoresis?
A: Ninhydrin
98
What color appears when ninhydrin reacts with a primary amino acid?
A: Purple
99
What does the number of purple spots indicate?
A: The number of primary amino acids present
100
Which amino acid gives a different color with ninhydrin and why?
A: Proline, because it’s a secondary amine; gives a yellow product
101
What is electrophoresis mainly used for in amino acid analysis?
A: Identifying and counting different amino acids in a mixture
102
Can electrophoresis be used to isolate amino acids in bulk?
A: No, it is not suitable for large-scale separation
103
What technique is used for preparative amino acid separation?
A: Column chromatography
104
Latent Fingerprints and Amino Acids
Latent fingerprints are invisible prints left on surfaces by residues from the skin — mainly sweat (~99% water).
Sweat contains trace organic compounds, including amino acids.
These amino acids:
Are present in small amounts
Are chemically stable over time
Allow detection long after the print is made
105
Ninhydrin Reaction
Ninhydrin is a reagent that reacts with amino acids, specifically primary amines.
When ninhydrin contacts the amino acids in the fingerprint residue, it forms a fluorescent purple compound.
This reaction reveals the pattern of the fingerprint.
The product is the same purple compound formed during amino acid analysis.
Application Procedure
A solution of ninhydrin is sprayed on the suspected surface.
Mild heating is applied to accelerate the reaction.
Within a few minutes to hours:
The purple prints appear.
These images are then photographed or analyzed.
⚠️ Limitations
Background staining may occur, reducing image contrast.
Light fading may affect the longevity of the image.
Development can be slow (up to 2 weeks) if not accelerated by heat
106
Ninhydrin Analogues
Over the years, modified versions (analogues) of ninhydrin have been developed.
These analogues:
Aim to improve contrast, sensitivity, or development speed.
Include additional functional groups like Cl or OMe (methoxy).
But most are not widely adopted due to:
High cost
Only slight improvements
107
Amino Acid Synthesis via α-Haloacids
This is one of the oldest and most classical methods of synthesizing α-amino acids, especially racemic mixtures. It is a two-step process:
Step 1: α-Halogenation of a Carboxylic Acid
This uses the Hell–Volhard–Zelinsky (HVZ) Reaction.
Reagents:
Br₂ + PBr₃ (to convert the –COOH into an acyl bromide and enable α-enolization)
H₂O (to hydrolyze back to the acid)
Reaction:
R–CH₂–COOH
→
𝐵
𝑟
2
,
𝑃
𝐵
𝑟
3
R–CH(Br)–COOH
R–CH₂–COOH
Br
2
,PBr
3
R–CH(Br)–COOH
The result is a racemic α-bromo acid (a mixture of R and S enantiomers).
Step 2: Substitution with Ammonia (SN2 Reaction)
The α-bromo group is replaced with an amino group (–NH₂) using excess NH₃.
This is a nucleophilic substitution (SN2 mechanism).
Reaction:
R–CH(Br)–COOH
→
𝑒
𝑥
𝑐
𝑒
𝑠
𝑠
𝑁
𝐻
3
R–CH(NH₂)–COOH
R–CH(Br)–COOH
excessNH
3
R–CH(NH₂)–COOH
Final product: Racemic α-amino acid.
⚠️ Special Note on Polyalkylation
In general, ammonia reacting with alkyl halides leads to polyalkylation (multiple substitutions).
But in this reaction:
The α-halo acid is sterically hindered.
That prevents multiple alkylations, so only one NH₂ is added.
108
What classic method is used to synthesize α-amino acids from carboxylic acids?
A: The Hell–Volhard–Zelinsky (HVZ) reaction followed by SN2 substitution with ammonia.
109
What type of amino acid mixture is produced using this method?
A: A racemic mixture (50:50 R and S enantiomers).
110
What reagents are used to brominate the α-carbon of a carboxylic acid?
A: Br₂ + PBr₃, followed by H₂O
111
What reagent is used to substitute Br with NH₂?
A: Excess NH₃
112
What kind of mechanism is used to replace Br with NH₂?
A: SN2 nucleophilic substitution
113
What structural feature is introduced at the α-carbon during Amino Acid Synthesis via α-Haloacids?
A: A new chiral center, leading to R and S enantiomers
114
What functional groups are present in the final α-amino acid? Amino Acid Synthesis via α-Haloacids
A: An amino group (–NH₂) at the α-carbon, and a carboxylic acid (–COOH)
115
Amino Acid Synthesis via the Amidomalonate Synthesis
Background
This method is based on a clever adaptation of the malonic ester synthesis, which produces substituted carboxylic acids.
The starting material is diethyl acetamidomalonate — a malonic ester with an amide group (–NHAc) already built in.
116
Steps of the Reaction Amino Acid Synthesis via the Amidomalonate Synthesis
There are 3 main steps, similar to malonic ester synthesis
Step 1: Deprotonation
Reagent: NaOEt (a strong base)
The base removes the acidic proton from the α-carbon (between the two esters).
EtOOC–CH(NHAc)–COOEt
→
NaOEt
Carbanion
EtOOC–CH(NHAc)–COOEt
NaOEt
Carbanion
Step 2: Alkylation
Reagent: Alkyl halide (R–X)
The carbanion attacks the alkyl halide (SN2), forming a new C–C bond at the α-carbon.
Carbanion
+
𝑅
–
𝑋
→
EtOOC–CH(R)(NHAc)–COOEt
Carbanion+R–X→EtOOC–CH(R)(NHAc)–COOEt
Step 3: Hydrolysis and Decarboxylation
Reagents: H₃O⁺, Heat
Both ester groups are hydrolyzed to carboxylic acids.
One COOH group is decarboxylated (lost as CO₂).
The amide is also hydrolyzed to a primary amine (–NH₂).
EtOOC–CH(R)(NHAc)–COOEt
→
H₃O⁺, Heat
H₂N–CH(R)–COOH
EtOOC–CH(R)(NHAc)–COOEt
H₃O⁺, Heat
H₂N–CH(R)–COOH
✅ Result: A racemic α-amino acid
💡 Key Insight
The identity of the final amino acid is determined by the alkyl halide used in step 2.
For example, using benzyl bromide gives phenylalanine.
117
What is the starting material in amidomalonate synthesis?
A: Diethyl acetamidomalonate
118
What is the purpose of the amidomalonate synthesis?
A: To synthesize racemic α-amino acids
119
What functional group in the starting material will eventually become the amino group?
A: The amide group (–NHAc)
120
What happens in Step 1 of amidomalonate synthesis?
A: Deprotonation at the α-carbon using NaOEt
121
What happens in Step 2 amidomalonate synthesis?
A: Alkylation with an alkyl halide (R–X) via an SN2 mechanism
122
What happens in Step 3. amidomalonate synthesis?
Hydrolysis of esters and amide, followed by decarboxylation of one COOH group
123
Is the product optically active? amidomalonate synthesis
A: No — it's a racemic mixture
124
What determines the identity of the final amino acid? amidomalonate synthesis
A: The R group introduced by the alkyl halide in Step 2
125
STRECKER SYNTHESIS OVERVIEW
Purpose:
To synthesize racemic α-amino acids from aldehydes in two steps:
Formation of an α-amino nitrile
Hydrolysis of the nitrile to a carboxylic acid
Reagents:
NH₄Cl (provides NH₃)
NaCN (source of nucleophilic cyanide)
H₃O⁺ (acidic hydrolysis)
General Reaction: Aldehyde → α-amino nitrile → α-amino acid
RCHO → RCH(NH₂)CN → RCH(NH₃⁺)COO⁻
126
DETAILED MECHANISM STRECKER SYNTHESIS
Step 1: Imine Formation
Nucleophilic attack: NH₃ attacks the carbonyl carbon of the aldehyde.
Proton transfers create a stable imine intermediate.
Step 2: Nitrile Formation
Cyanide ion (⁻C≡N) attacks the imine carbon.
This gives an α-amino nitrile.
Step 3: Hydrolysis of the nitrile
Under acidic conditions, the nitrile undergoes hydrolysis.
Forms a carboxylic acid group → yielding a racemic α-amino acid.
127
What is the starting material for the Strecker synthesis?
A: An aldehyde.
128
What type of amino acid does Strecker synthesis produce?
A: A racemic mixture of α-amino acids (both D and L forms).
129
Which nucleophile attacks the aldehyde in Strecker synthesis?
A: Ammonia (NH₃), forming an imine.
130
What is the role of NaCN in the Strecker synthesis?
A: Provides cyanide ion (⁻C≡N) for nucleophilic attack on the imine.
131
What intermediate is formed after the cyanide attack?
A: α-Amino nitrile.
132
How is the nitrile converted into a carboxylic acid?
A: By acidic hydrolysis using H₃O⁺ and heat.
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What determines the identity of the amino acid formed?
A: The structure of the starting aldehyde.
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Why is the product racemic?
(strecker synthesis )
A: The carbon becomes a chiral center, and the reaction is not stereoselective.
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Enantioselective Synthesis of L-Amino Acids
When amino acids are synthesized in the laboratory through most common methods (e.g., Strecker synthesis, reductive amination, or malonic ester synthesis), the result is usually a racemic mixture of both enantiomers (D and L forms). However, in biological systems, only L-amino acids are used to build proteins. Therefore, synthesizing optically active (chiral) L-amino acids requires one of two strategies:
Resolution of racemic mixtures (less efficient because half of the material is wasted).
Enantioselective synthesis (preferred due to higher efficiency and reduced waste).
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Enantioselective Synthesis Example: Knowles' Procedure
Enantioselective Synthesis Example: Knowles' Procedure
The strategy used by Knowles involves asymmetric hydrogenation of a prochiral double bond.
A chiral catalyst is employed to reduce the double bond in a way that produces one enantiomer preferentially, such as the (S)-enantiomer of L-dopa.
Example Reaction:
A substrate containing a C=C bond next to a carbonyl group undergoes asymmetric hydrogenation using a chiral ruthenium catalyst complexed with (R)-BINAP.
This results in the (S)-enantiomer of an amino acid (e.g., L-dopa).
Why BINAP?
BINAP is a chiral phosphine ligand.
When bound to Ru, it gives a chiral environment that biases the face of the double bond being attacked during hydrogenation.
This bias allows for control over stereochemistry, often yielding >99% enantiomeric excess (%ee).
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What is the main advantage of enantioselective synthesis over resolution of racemic mixtures?
A: It avoids waste by producing only one enantiomer directly, making the process more efficient.
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What type of catalyst is used in asymmetric hydrogenation to synthesize L-amino acids?
A: A chiral metal catalyst, often ruthenium complexed with BINAP.
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What is BINAP?
A: (R)-BINAP is a chiral phosphine ligand used in asymmetric catalysis to control enantioselectivity.
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What product is formed by asymmetric hydrogenation in the synthesis of L-dopa?
A: (S)-3,4-Dihydroxyphenylalanine (L-dopa).
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What does "% ee" stand for and what does it measure?
A: Enantiomeric excess; it measures the purity of one enantiomer over the other in a chiral product.
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What role does the chiral catalyst play in the hydrogenation process?
A: It ensures that hydrogen is added to one face of the double bond preferentially, leading to one enantiomer.
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Which amino acid was synthesized with 99% ee using (R)-Ru(BINAP)Cl2?
A: D-Phenylalanine.
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Why is enantioselective synthesis important in pharmaceutical and biological chemistry?
A: Because only one enantiomer (usually L-form) is biologically active and functional in proteins.
