R/S Configuration and Stereochemistry

• Stereochemistry distinguishes stereoisomers, achieved using the Cahn-Ingold-Prelog system.
• This system assigns 'R' (from Latin rectus, right-handed) or 'S' (from Latin sinister, left-handed) designations to stereocenters.

Assigning R/S Configuration

• Assign priorities to the four substituents of a chiral center, #1 being highest and #4 lowest, based on atomic number.
• Trace a circle from priority #1 to #2 to #3.
• If the #4 priority group points away, a clockwise circle indicates R configuration, counterclockwise indicates S.
• If the #4 priority group points toward you, a clockwise circle indicates S configuration, counterclockwise indicates R.

R/S Configuration Example: Glyceraldehyde

• Two priorities in glyceraldehyde are straightforward: hydrogen (#4) and hydroxyl oxygen (#1).
• Comparing aldehyde vs. CH2OH, the aldehyde group is #2 due to its double bond to oxygen, while CH2OH is #3.
• The #4 priority group (hydrogen) points away, so tracing the circle determines that glyceraldehyde has 'R' configuration.
• (R)-glyceraldehyde, its enantiomer is (S)-glyceraldehyde.

R/S Configuration Example: Lactic Acid

• The #4 priority group points towards
• Clockwise direction = S configuration

Thalidomide

• Thalidomide's stereochemistry led to tragic consequences in drug design.
• It was first made by a German company and prescribed for morning sickness during pregnancy in Europe/Australia in the 1950s.
• This drug was quickly linked to devastating birth defects in babies.
• Thalidomide exists in two enantiomeric forms due to a chiral center.
• Marketed as a 50:50 racemic mixture.
• Four bonds configuration: The nitrogen group is #1, carbonyl side is #2, and -CH2 side is #3.

Glyceraldehyde Forms and the d/I System

• Glyceraldehyde, the simplest carbohydrate, has two isomeric mirror-image forms.
• The d/I system (Latin dexter/laevus, right/left) names molecules by relating them to glyceraldehyde, and is unrelated to (+)/(−) labeling.
• (+)/(−) does not indicate which enantiomer is dextrorotatory or levorotatory

Naming Stereoisomers with Multiple Chiral Centers

• Focus on the chiral carbon furthest from the carbonyl group to name stereoisomers with multiple chiral centers.
• The hydroxy group pointing right when the carbonyl is "up" indicates the D-isomer, to the left is the L-isomer.

Stereoisomers and Chirality

• Stereoisomers are forms of each other.
• Glyceraldehyde: a chiral molecule, unsuperimposable on mirror image; mirror-image forms are enantiomers.
• Chiral molecules share the same relationship as left and right hands reflected in a mirror.

Chiral Carbons Defined

• Chiral objects can’t be superimposed on mirror images (hands, gloves, shoes).
• Achiral objects can be superimposed on the mirror images (drinking glasses, spheres, and cubes).
• A carbon connected to four different groups is chiral, and it has two nonsuperimposable mirror images.

Examples: Chiral and Achiral Molecules

• If any two groups attached to a carbon atom are the same, the carbon atom cannot be chiral.
• Many organic compounds, carbs, contain more than one chiral carbon.

The 2^n Rule for Stereoisomers

• Each chiral carbon can be arranged in right- or left-hand form if a molecule has more than one chiral carbon.
• n chiral carbons yields 2^n possible stereoisomers.
• Maximum number of possible stereoisomers = 2^n

Fischer Projections

• Fischer projections represents mirror images in two dimensions.
• Position the carbonyl group at the top and the last achiral CH2OH at the bottom.

Fischer Projections applied to Monosaccharides

• Linear structure projections of a monosaccharide use Fischer projection
• Aldehyde sugars are aldoses.
• Ketone sugars are ketoses.
• They are polyhydroxy aldehydes/ketones or compounds that produce such substances upon hydrolysis.

Steps for Drawing Fischer Structures of Sugars

• Sort monosaccharides by carbon chain length. -Write the carbon chain vertically with aldehyde/ketone towards the top.
• Number the carbons.
• Place the aldehyde or ketone group.
• Place H and OH groups.
• Identify chiral centers.
• Note the highest numbered chiral center to distinguish D and L sugars.
• Write the correct common name for the sugar.

Fischer Projections example

• Draw Fischer projections of D and L lactic acid/alanine.
• Given structure for D-glucose, draw structure of L-glucose.
• Identify compounds as D or L isomers, and draw their mirror images.

Cyclization: Haworth Projections

• The Haworth projection shows cyclic forms: α- and β-forms.
• Sugars usually exist in a cyclic hemiacetal form show as haworth projection.
• Less than 1% of sugar is linear in solution (Fischer structure).
• Over 99% have cyclic ring structure (Haworth structures).
• The preferred ring form varies, some prefer to be a 6-member ring "pyranose", for example, glucose.

Aldehyde and Ketone Sugars

• Aldehyde sugar/aldoses + alcohol yield hemiacetal (cyclic ring).
• Ketone sugar/ketoses + alcohol yield hemiketal (cyclic ring).
• Polyhydroxy aldehydes (like glucose) or ketones (like fructose) / compounds that produce such substances upon hydrolysis

Molecules and Polarized Light

• Molecules that are enantiomers have the same physical properties but differ in their interaction with polarized light.
• Polarized light vibrates in one plane only.
• Rotated by passing light through a polarizing filter.

Optical Activity

• Levorotatory (-) substances rotate polarized light to the left.
• Dextrorotatory (+) substances rotate polarized light to the right.
• Molecules which rotate the plane of polarized light are optically active.
• Living systems often use single stereochemical forms (chiral + optically active).
• L-lactic acid is in living muscles; D-lactic acid is in sour milk.
• Enantiomer molecule can be beneficial or toxic ( ex Thalidomide)
• Humans can metabolize D-monosaccharides not L-isomers; only L-amino acids are used in protein synthesis.

Glycoside Formation (Acetal and Ketal Structures)

• The hemiacetal and hemiketal forms of monosaccharides can react with alcohols to form glycosides.
• The new carbon-oxygen bond is the glycosidic linkage.

Important Disaccharides

• Lactose comprises 5% of cow's milk and 7% of human milk, digestion needs lactase, pure lactose is byproduct found in whey water of cheese production.
• Maltose also known as malt sugar.
• Both use are β(1→4) glycosidic linkage

Oligosaccharides Defined

• Oligosaccharides contain from 3 to 10 monosaccharide units.
• Raffinose is found in peas/beans and is undigested until in the large intestine, releasing hydrogen, carbon dioxide, and methane.

Polysaccharides Defined

• Polysaccharides contain hundreds/thousands of carbohydrate units.
• Are not reducing sugars
• Anomeric carbons are linked by glycosidic linkages.
• Polymers of glucose: starch, glycogen, and cellulose.

Starch composed of D-Glucose

• Starches (and other glucose polymers) are usually water insoluble because of high molecular weight
• Contain numbers of OH groups, so some starches can form thick colloidal dispersions with heated water.
• Two types: Amylose and amylopectin

Starch: Amylose

• Consists of unbranched chains of glucose (1000 to 2000 molecules)
• Connected by α(1→4) glycosidic linkages.
• 10%-20% of the starch in plants.
• Helical molecules.
• Packs more tightly and they digest slower than starches.
• Amylose helices can trap molecules of iodine, turns deep blue-purple.
• Iodine often used as a test for the presence of starch.

Starch: Amylopectin

• Long chains of glucose (up to 105 molecules) connected by α(1→4) glycosidic
• α(1→6) branches every 24-30 glucose units along the chain.
• This form is 80%-90% of plant starch.

Glycogen, Animal Starch

• Glycogen composition is similar to amylopectin
• Has both α(1→4) glycosidic linkages and α(1→6) branch points.
• Glycogen is highly branched, with branches occurring every 8 to 12 glucose units.
• Abundant in the liver and muscles. On hydrolysis it forms D-glucose to maintain normal blood sugar level and provides energy

Starch and Glycogen Structures

• Amylose is unbranched
• Amylopectin is branched
• Glycogen highly branched

Cellulose Defined

• Cellulose is a polymer of long, unbranched chains of D-glucose connected by β(1→4) glycosidic linkages
• Each molecule contain 300 to 3000 glucose units
• The β-linkages give it different overall shape compared to amylose.

Qualities and Importance of Cellulose

• Forming straight chains which hydrogen bond to each other
• Giving a very rigid structure.
• The most important structural polysaccharide.
• The most abundant compound on earth.
• It is the material in plant cell walls that provides strength and rigidity; wood is 50% cellulose.

Nitrocellulose, Celluloid, and Rayon

• Cotton treated with nitric/sulfuric acids.
• Guncotton discovered by Christian Friedrich Schönbein in 1845.
• Cordite replaced it when it was proved dangerous (James Dewar, Frederick Abel, 1891)
• Nitroglycerine and petroleum jelly a mixture made of nitrocellulose
• Celluloid (Hyatt, 1869): 1st synthetic plastic, cellulose with alcohol/ether/ camphor. Used for billiard balls /photographic film. Replaced by less flammable plastics
• Rayon (Chardonnet, 1884): cellulose mixed with solvents.

Dietary Fiber

• Complex carbs: Cellulouse and substances in cell walls structural parts of plants.
• Cereal grains/oatmeal/fresh produce, fruit, vegetables are great fiber sources.
• Pectin a soluble fiber with lower molecular weight is also more water soluble. Traps carbs and digestion, slows absorption that levels out blood sugar.
• Soluble fiber lowers cholesterol binding cholesterol.
• Insoluble fiber gives bulk to stool, and helps solid waste elimination.

Chitin

• Polymers of N-acetylglucosamine.
• Amide derivative to a glucosamine.
• The sugar’s OH chain converted to amine(NH2)
• Strong Polymers with hydrogen bonding in Amide.
• Main component in cell walls/fungi/ arthropods/ crustaceans/insects.

Sweeteners

• Steviol (Truvia), Pure Via- Stevia rebaudiana (sweetleaf) is from Stevia plants
• Steviol makes stevioside (250-300 times sweetener than sugar
• Steva contains additional rebiana glucose group 350-450 the glucose are FDA in 2009
• Saccharin is noncaloric and about 500 times sweeter than sugar. Discovered by Constantine Fahlberg 1879,
• Aspartame (NutraSweet) is about 160 times sweeter than sugar
• Cyclamate is used in combination with artifical sugars 30-50 times sweeter, discovered by Michael Sveda in 1937.
• Heat Stable Cyclamate banned in the FDS in 1970.
• Acesulfame-K (Sunette, Sweet One) discovered by a chemist accident dipped his fingers in chemical 200 X sweeter than sugar

Maillard Reaction

• Heating carbohydrates and proteins = Maillard Reaction
• Results from a complex mixture of products and the development of a brown color
• It happens when the grilling/ browing of meat/ and baking/toasting product food with carbohydrates and protein under heating.