lecture 28 get lp 9/10; due next tuesday sweeteners this week in lab: spec unknown final report due...
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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
OHO
HO
OH
OHO O
OH
OH
OH
OH
Sucrose
OHO
HO
OH
OHOH
Glucose
OOH
HO
HO
OH
OH
Fructose
Saccharin
• Non-carbohydrate sweetener• Sweet’N Low, Sugar Twin
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
S
NH
O
OO
• Safety controversy due to findings of bladder tumors in some male rats• More than 30 human studies conclude that it’s safe
Saccharin
Sweetness:
Shape must fit into specificreceptors in taste buds.
When shape is slightly modified, it is no longersweet:
S
NH
O
OO
S
N
O
OO
CH3
Aspartame
• Non-carbohydrate sweetener• Equal, NutraSweet
H
HN
OO
CH3
O
H3NH
O O
Methyl ester
Phenylalanine
Aspartic acid
Aspartame
Aspartame
Discovery story:• In 1965 by Jim Schlatterworking on discovering newtreatments for gastriculcers.• Made a dipeptide intermediate, which he spilled on his hand• Tested the dipeptide in coffee
H
HN
OO
CH3
O
H3NH
O O
Methyl ester
Phenylalanine
Aspartic acid
Aspartame
• 4 calories per gram• 200 times sweeter than sugar
Aspartame
Phenylalanine is an essential amino acid and is a precursor for the synthesis of tyrosine and severalneurotransmitters.
Excess phenylalanine is broken down intofumarate and acetoacetate - normal energy metabolism.
H
HN
OO
CH3
O
H3NH
O O
Methyl ester
Phenylalanine
Aspartic acid
Aspartame is metabolized in the body into:methanol (wood alcohol), phenylalanine, and aspartic acid
Aspartame
H
HN
OO
CH3
O
H3NH
O O
Methyl ester
Phenylalanine
Aspartic acid
Aspartame
Safety concerns:If lacking the enzyme to convertphenylalanine to tyrosine, havephenylketonuria, PKU.
Phenylalanine is then converted to phenylketones instead.
PKU could lead to mental retardation if not detected or treated.
Products that contain aspartame carry an information label for phenylketonurics.
Aspartame
H
HN
OO
CH3
O
H3NH
O O
Methyl ester
Phenylalanine
Aspartic acid
Aspartame
Safety concerns:
Reports of formaldehydepoisoning.
Methanol quickly converts toformaldehyde in the body.
Formaldehyde causes severe damage to the neurological system, immune system, and causes permanent genetic damage at extremely low doses.
Aspartame Synthesis
H
HN
OO
CH3
O
H3NH
O O
Methyl ester
Phenylalanine
Aspartic acid
Two main constituents:PhenylalanineAspartic acid
Goal:1. Make the methylester of phenylalanine2. Make a peptide (amide)bond between phenylalanineand aspartic acid
Overall - two main steps to this synthesis
Aspartame: Ester Synthesis
Only the S enantiomer of phenylalanine is desired for use. The R andS enantiomers can be separated before the esterification reaction.
NH2
O
OH*
Racemic phenyalanine(Both R & S enantiomers)
+ CH3OH
NH2
O
OCH3 +O
H H*
H+
Aspartame Synthesis: Amide Formation
NH2
O
OCH3
Phenylalanine
+
HO
O NH2
O
OH*
Aspartic Acid
Protect thisCO2H
H
HN
OO
CH3
O
H3NH
O O
Methyl es ter
Phenyla lanine
Aspartic acidNew amidebond
Protect this NH2
Sucralose/Splenda
• Carbohydrate-based sweetener• Made from sugar• 600 times sweeter than sugar
O
HO
OH
OHO O
Cl
Cl
HO
OH
Cl
O
HO
OH
OHO O
OH
OH
HO
OH
Sucrose Sucralose
HO
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
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
HO
OH
OHO O
Cl
Cl
OH
OH
Cl
Sucralose
Synthesis of Sucralose
O
HO
OH
OHO O
Cl
Cl
HO
OH
Cl
O
HO
OH
OHO O
OH
OH
HO
OH
Sucrose Sucralose
HO
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