Lecture 28
• Get LP 9/10; due next Tuesday
• Sweeteners
This Week in Lab:
Spec Unknown Final Report Due
Next Week in Lab:
• Synthetic #2 Final Report Due
• Remember to bring all graded PreLabs and Aldrich to lab
Sweeteners
Carbohydrates:
Mono- and disaccharides
Examples:
Sugar, corn syrup, maple syrup, juice concentrates
OH
HO
HO
O
OH
HO
OH
OH
O
O
HO
O
OH
Sucrose
OH
HO
OH
O
OH
HO
OH
OH
Glucose
OH
Fructose
OH
Saccharin
• Non-carbohydrate sweetener
• Sweet’N Low, Sugar Twin
O
NH
S
O
O
Discovery Story:
• In 1879 by Constantine Fahlberg
• By 1907, saccharin was used by diabetics
• Not metabolized in the body for energy
• By 1960s, used in diet soft drinks
• Safety controversy due to findings of bladder tumors
in some male rats
• More than 30 human studies conclude that it’s safe
Saccharin
Sweetness:
O
Shape must fit into specific
receptors in taste buds.
NH
S
O
When shape is slightly modified, it is no longer
sweet:
O
N
S
O
O
CH3
O
Aspartame
• Non-carbohydrate sweetener
• Equal, NutraSweet
CH3
O
O
Methyl ester
H
Phenylalanine
HN
H3N
O
Aspartic acid
H
O
O
Aspartame
Aspartame
CH3
Discovery story:
• In 1965 by Jim Schlatter
working on discovering new
treatments for gastric
ulcers.
• Made a dipeptide intermediate,
which he spilled on his hand
• Tested the dipeptide in coffee
• 4 calories per gram
• 200 times sweeter than sugar
O
O
Methyl ester
H
Phenylalanine
HN
H3N
O
Aspartic acid
H
O
O
Aspartame
Aspartame
Aspartame is metabolized in the body into:
methanol (wood alcohol), phenylalanine, and aspartic acid
CH3
O
O
Methyl ester
H
Phenylalanine
HN
H3N
O
Aspartic acid
H
O
O
Phenylalanine is an essential amino acid and is a
precursor for the synthesis of tyrosine and several
neurotransmitters.
Excess phenylalanine is broken down into
fumarate and acetoacetate - normal energy metabolism.
Aspartame
CH3
Safety concerns:
If lacking the enzyme to convert
phenylalanine to tyrosine, have
phenylketonuria, PKU.
O
Methyl ester
H
Phenylalanine
HN
H3N
Phenylalanine is then converted to
phenylketones instead.
O
O
Aspartic acid
H
O
O
Aspartame
PKU could lead to mental retardation
if not detected or treated.
Products that contain aspartame carry an information
label for phenylketonurics.
Aspartame
CH3
Safety concerns:
Reports of formaldehyde
poisoning.
O
Formaldehyde causes severe
damage to the neurological system,
immune system, and causes
permanent genetic damage at
extremely low doses.
Methyl ester
H
Phenylalanine
HN
H3N
Methanol quickly converts to
formaldehyde in the body.
O
O
Aspartic acid
H
O
O
Aspartame
Aspartame Synthesis
CH3
O
O
Methyl ester
H
Phenylalanine
HN
H3N
O
Aspartic acid
H
O
O
Two main constituents:
Phenylalanine
Aspartic acid
Goal:
1. Make the methyl
ester of phenylalanine
2. Make a peptide (amide)
bond between phenylalanine
and aspartic acid
Overall - two main steps to this synthesis
Aspartame: Ester Synthesis
NH2
+
OH
CH3OH
*
O
Racemic phenyalanine
(Both R & S enantiomers)
H+
NH2
OCH3
*
+
O
H
H
O
Only the S enantiomer of phenylalanine is desired for use. The R and
S enantiomers can be separated before the esterification reaction.
Aspartame Synthesis: Amide Formation
Protect this
CO2H
O
Protect this NH2
NH2
NH2
+
OCH3
OH
HO
*
O
O
Phenylalanine
Aspartic Acid
CH3
O
O
Methyl ester
H
Phenylalanine
HN
New amide
bond
H3N
O
Aspartic acid
H
O
O
Sucralose/Splenda
• Carbohydrate-based sweetener
• Made from sugar
• 600 times sweeter than sugar
OH
HO
HO
Cl
OH
O
O
HO
OH
OH
O
O
O
Sucrose
O
HO
HO
OH
Cl
OH
OH
OH
Sucralose
Cl
Sucralose/Splenda
• Does not metabolize to produce energy, thus no calories
• Only low calorie sweetener made from sugar
• Heat stable - used in cooking and
baking
Cl
OH
O
HO
Cl
OH
O
Discovery story:
• In 1976 by Dr. Hough’s lab
at King’s College
• From 1980 onwards, collaboration
with Tate & Lyle, a British sugar company,
and McNeil Specialty Products
O
OH
OH
Sucralose
Cl
Synthesis of Sucralose
OH
HO
HO
Cl
OH
O
O
HO
OH
OH
O
O
O
Sucrose
O
HO
HO
OH
Cl
OH
OH
OH
Cl
Sucralose
6-step reaction sequence:
(1) React sucrose with tritylating agent
(2) Acetylation of product from step (1)
(3) Detritylation of step (2) product
(4) Isomerization of the penta-acetate product from step (3)
(5) Chlorination of step (4) product
(6) Deacetylation of step (5) product