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

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

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

Aspartame Non-carbohydrate sweetener Equal, NutraSweet Aspartame

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

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.

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.

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

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

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.

Aspartame Synthesis: Amide Formation

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

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

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