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Organic Chemistry 2 Unit 10: Biomolecules: Carbohydrates, Amino Acids, Lipids

Carbohydrates, amino acids and lipids are organic molecules whose behavior follows the same rules as the rest of the course: hemiacetal formation, oxidation and reduction of carbonyls, acid–base equilibria, amide bonds and ester hydrolysis.

Covers: Monosaccharides: classification, D/L and Fischer projections, Cyclic forms, anomers and mutarotation, Reactions of sugars: reduction, oxidation and glycosides, Disaccharides and polysaccharides, Amino acids, zwitterions and isoelectric points, Peptides and peptide synthesis, Lipids: fatty acids, triglycerides, phospholipids and steroids

Study guide

Monosaccharides are polyhydroxy aldehydes (aldoses) or ketones (ketoses), classified by carbon count: glucose is an aldohexose and fructose is a ketohexose. They are drawn in Fischer projections, with the carbonyl at the top; horizontal bonds point toward the viewer. The D or L label depends only on the stereocenter farthest from the carbonyl: if its OH is on the right, the sugar is D. Nearly all natural sugars are D. An aldohexose has four stereocenters, so there are 2⁴ = 16 stereoisomers, eight D and eight L. Sugars that differ at only one stereocenter are epimers: D-glucose and D-mannose are C2 epimers, and D-glucose and D-galactose are C4 epimers.

In water, sugars exist mainly as cyclic hemiacetals formed when the C5 OH attacks the C1 aldehyde, giving a six-membered pyranose ring (five-membered rings are furanoses). Cyclization creates a new stereocenter at C1, the anomeric carbon, so there are two anomers: in the Haworth projection of a D-sugar, the α anomer has its anomeric OH on the opposite side of the ring from C6 (down), and the β anomer has it on the same side (up). In the chair form of β-D-glucopyranose every substituent is equatorial, which is why it is the most abundant form. Pure α-D-glucose (+112°) or β-D-glucose (+18.7°) changes in water to an equilibrium rotation of +52.7°, a process called mutarotation that occurs through the open-chain aldehyde; the equilibrium is about 64% β.

Sugar reactions are carbonyl and alcohol reactions. NaBH₄ reduces the open-chain aldehyde to an alditol: glucose gives glucitol (sorbitol). Mild oxidants (Br₂ water, Tollens' or Benedict's reagent) oxidize C1 to an aldonic acid; any sugar that reacts is a reducing sugar, which requires a free hemiacetal. Warm HNO₃ oxidizes both ends to an aldaric acid, which can be meso when the molecule becomes symmetric, as for D-galactose. An alcohol with acid catalysis converts the hemiacetal into an acetal called a glycoside; glycosides cannot open, so they do not mutarotate and are nonreducing. Disaccharides are glycosides of a second sugar. Maltose (α-1,4) and lactose (β-1,4) are reducing sugars, but sucrose is not, because its glycosidic bond joins the anomeric carbons of both glucose and fructose. Humans digest starch and glycogen (α-1,4 glucose polymers) but not cellulose (β-1,4).

The 20 common amino acids have the structure H₃N⁺–CHR–COO⁻ at physiological pH; this zwitterion has both charges. All except glycine are chiral, and natural amino acids are L, which is (S) for all except cysteine. Each amino acid has a carboxyl pKa near 2 and an ammonium pKa near 9 to 10, and some side chains ionize too. The isoelectric point (pI) is the pH at which the net charge is zero: for a neutral side chain, pI is the average of the two pKa values (glycine: (2.34 + 9.60)/2 = 5.97). For acidic amino acids, average the two acidic pKa values; for basic ones, average the two basic pKa values. At a pH below the pI the molecule is net positive and moves toward the cathode in electrophoresis; above the pI it is net negative.

Peptides are chains of amino acids joined by amide (peptide) bonds, written from the N-terminus to the C-terminus. The peptide bond is planar, with partial double-bond character from amide resonance. In laboratory peptide synthesis, the amino group of one amino acid is protected (for example with Boc or Fmoc) and the carboxyl of the other is protected (as an ester), and a coupling agent such as DCC activates the free carboxyl, so that only the desired amide forms. Lipids are defined by solubility in nonpolar solvents. Triglycerides are triesters of glycerol and fatty acids; saponification with NaOH gives glycerol and soap. Cis double bonds in unsaturated fatty acids put kinks in the chains, lowering melting points, so vegetable oils are liquids. Phospholipids form membranes, and steroids such as cholesterol share a fused four-ring skeleton.

Key ideas

• D or L is set by the OH on the stereocenter farthest from the carbonyl in a Fischer projection.
• Sugars cyclize to hemiacetals, creating α and β anomers that interconvert by mutarotation.
• A free hemiacetal makes a sugar reducing; glycosides and sucrose are nonreducing.
• Glycosidic linkage type (α versus β) determines whether a polysaccharide is starch-like or cellulose-like.
• Amino acids are zwitterions, and pI is the average of the pKa values on either side of the neutral form.
• Peptide synthesis requires protecting groups and a coupling agent to control which amide forms.
• Triglycerides are esters that undergo saponification; cis unsaturation lowers melting points.

Formulas and rules

Common mistakes

• Assigning D or L from C2 instead of from the stereocenter farthest from the carbonyl.
• Thinking anomers are enantiomers; they are diastereomers that differ only at the anomeric carbon.
• Calling sucrose a reducing sugar because it contains glucose.
• Averaging the wrong pair of pKa values when finding the pI of an acidic or basic amino acid.
• Forgetting that peptides are written from the N-terminus to the C-terminus.

Before the test, make sure you can

• Classify monosaccharides and assign D/L from Fischer projections.
• Draw the cyclic forms of glucose and identify α and β anomers.
• Calculate the anomer composition at mutarotation equilibrium.
• Predict products of sugar reduction, oxidation and glycoside formation, and identify reducing sugars.
• Compare starch, glycogen and cellulose in terms of glycosidic linkages.
• Calculate the pI of neutral, acidic and basic amino acids and predict net charge at a given pH.
• Explain the role of protecting groups and coupling agents in peptide synthesis.
• Describe triglyceride saponification and relate fatty acid structure to melting point.

Words to know

Aldose

A monosaccharide containing an aldehyde group, such as glucose.

Ketose

A monosaccharide containing a ketone group, such as fructose.

D-sugar

A sugar whose stereocenter farthest from the carbonyl has its OH on the right in a Fischer projection.

Epimers

Diastereomers that differ in configuration at only one stereocenter, such as D-glucose and D-mannose.

Pyranose

A six-membered cyclic hemiacetal form of a sugar.

Anomeric carbon

The hemiacetal carbon (C1 in aldoses) created when a sugar cyclizes.

Anomers

Cyclic sugar diastereomers that differ only at the anomeric carbon, labeled α and β.

Mutarotation

The change in optical rotation as α and β anomers interconvert through the open-chain form.

Reducing sugar

A sugar with a free hemiacetal that can be oxidized by Tollens' or Benedict's reagent.

Glycoside

An acetal formed from a sugar's anomeric carbon and an alcohol; it does not mutarotate.

Glycosidic bond

The C–O–C linkage joining sugars in disaccharides and polysaccharides.

Zwitterion

A neutral molecule bearing both a positive and a negative charge, such as H₃N⁺CHRCOO⁻.

Isoelectric point (pI)

The pH at which an amino acid or protein has zero net charge.

Peptide bond

The planar amide bond linking the carboxyl of one amino acid to the amino group of the next.

Protecting group

A group such as Boc, Fmoc or an ester that temporarily blocks an amino or carboxyl group.

Triglyceride

A triester of glycerol with three fatty acids, the main form of stored fat.

Phospholipid

A glycerol-based lipid with two fatty acid chains and a phosphate head group that forms membranes.

Steroid

A lipid built on a fused system of three six-membered rings and one five-membered ring, such as cholesterol.

Sample practice questions

30 more questions like these, from level 1 to 5, are in the practice set.