1. 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

2. Sweeteners Carbohydrates: Mono- and disaccharides Examples:
Sugar, corn syrup, maple syrup, juice concentrates

3. 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
Safety controversy due to findings of bladder tumors
in some male rats
More than 30 human studies conclude that it’s safe

4. Saccharin Sweetness: Shape must fit into specific
receptors in taste buds.
When shape is slightly modified, it is no longer
sweet:

5. Aspartame
Non-carbohydrate sweetener
Equal, NutraSweet
Aspartame

6. Aspartame 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
Aspartame
4 calories per gram
200 times sweeter than sugar

7. Aspartame Aspartame is metabolized in the body into:
methanol (wood alcohol), phenylalanine, and aspartic acid
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.

8. Aspartame Safety concerns: If lacking the enzyme to convert
phenylalanine to tyrosine, have
phenylketonuria, PKU.
Phenylalanine is then converted to phenylketones instead.
PKU could lead to mental retardation if not detected or treated.
Aspartame
Products that contain aspartame carry an information
label for phenylketonurics.

9. Aspartame Safety concerns: Reports of formaldehyde poisoning.
Methanol quickly converts to
formaldehyde in the body.
Formaldehyde causes severe damage to the neurological system, immune system, and causes permanent genetic damage at extremely low doses.
Aspartame

10. Aspartame Synthesis Two main constituents: Phenylalanine Aspartic acid
Goal:
Make the methyl
ester of phenylalanine
2. Make a peptide (amide)
bond between phenylalanine
and aspartic acid
Overall - two main steps to this synthesis

11. Aspartame: Ester Synthesis
Only the S enantiomer of phenylalanine is desired for use. The R and
S enantiomers can be separated before the esterification reaction.

12. Aspartame Synthesis: Amide Formation

13. Sucralose/Splenda Carbohydrate-based sweetener Made from sugar
600 times sweeter than sugar

14. 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

15. Synthesis of Sucralose
6-step reaction sequence:
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