lecture 28 get lp 9/10; due next tuesday sweeteners this week in lab: spec unknown final report due...

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