Properties of Monosaccharides

12:40 PM 1 Properties of Monosaccharides Optical Activity • Monosaccharides are non-superimposable on their mirror images and are thus chiral and optically active. • Optical activity is the ability of a compound to rotate the plane of polarized light. • The degree of rotation of the plane of polarized light, usually measured with a polarimeter, is commonly represented as specific rotation.

Carbohydrate Specific Carbohydrate Specific rotation rotation D-Glucose +52.7 D-Galactose +80.2 D-Fructose -92.4 D-Mannose +14.2 D-Arabinose -105.0 Lactose +55.4 L-Arabinose +104.5 Sucrose +66.5

Maltose +130.4 Invert sugar -19.8 12:40 PM 2 Properties of Monosaccharides Mutarotation • The prefix muta- refers to change. • Mutarotation is the change in specific rotation of a solution of any one of a pair of pure anomers of a sugar to an equilibrium or intermediate optical rotation.

Mutarotation

Pure anomer Equilibrium mixture of anomers Pure anomer

OH OH OH H H H H OH H O H H O H2O H HO H O HO O HO HO O 2 + H H OH OH HO H HO H HO H HO H OH OH OH OH H OH H OH H H H H -D-Glucopyranose -D-Glucopyranose -D-Glucopyranose (36%) -D-Glucopyranose (64%)

Change in specific optical rotation Change in specific optical rotation o ] +112.2o ] +52.6o [] +18.7

• When one of either the  or -anomer of glucose is dissolved in water, an interesting change in specific rotation is observed. 3 Anomerization of Monosaccharides: The Cause of Mutarotation • Anomerization is the interconversion between two anomers of a sugar in solution as a result of the existence of an equilibrium between the two anomers (cyclic hemiacetals) through a common linear aldehyde intermediate.

CHO Anomerization H OH HO H H OH H OH

CH2OH Fischer projection OH H OH OH H OH H H H HO O + + H H H OH H HO O HO H OH HO H HO H H O HO OH OH HO H H H OH OH HO H OH H O OH H H H H -D-Glucopyranose -D-Glucopyranose Free bond rotation • Once in the linear aldehyde intermediate, free bond rotation on C-1, makes it possible for recyclization to the hemiacetal form to occur to yield any one of two possible anomers. 12:40 PM 4 • This results in the mutarotation of the sugar. Properties of Monosaccharides Percentage Composition of Anomers on Mutarotation

• The phenomenon of mutarotation (change of optical rotation of a substrate to an intermediate value) is a consequence of the existence of a reversible equilibrium through an open chain intermediate via which the  and -anomers of the hemiacetal interconvert.

Sample Question and Calculation: • The specific optical rotations of pure  and -D- glucopyranoses are +112.2o and +18.7o, respectively. Assuming that only the - and -pyranoses are present; calculate the percentage of each anomer present in an equilibrium mixture of specific rotation +52.6o.

12:40 PM 5 Properties of Monosaccharides Percentage Composition of Anomers during Mutarotation Solution:

12:40 PM 6 Properties of Monosaccharides Anomeric Effect

• Monosaccharides in the pyranose form exist as mixtures of anomers ( and -anomers), whose ratio is determined by two competing and opposing factors: 1. The steric influence of the hydroxyl group at the anomeric carbon and 2. The electronic effect of the hemi-acetal oxygens. • The equatorially positioned substituents of a carbohydrate ring are, for steric reasons, the most energetically favoured, compared to the axial counterparts, as is the case with every molecule with a chair conformation.

12:40 PM 7 Properties of Monosaccharides Anomeric Effect: The Steric Factor Steric factor

OH HO HO O HO O HO H HO O Equatorial substituent HO HO H O H Axial substituent H Sterically favourable -anomer -anomer Sterically unfavourable because it allows for the unfavourable 1,3-diaxial interactions • However, the anomerically bound groups in carbohydrates do not follow this rule completely: D-pyranoses with the anomeric group located in an axial position are often more thermodynamically stable than would be predicted from the steric interactions they have with adjacent substituents.

12:40 PM 8 Properties of Monosaccharides Anomeric Effect: The Electronic Factor Electronic factor

HO OH HO O Lone pair electron Closer proximity of the HO H orbitals far apart and O electron pairs leading HO HO to a stronger electron hence less interaction HO O O H HO H repulsion and H destabilization -anomer -anomer Anomer which is favoured by the anomeric effect • The anomeric effect is a phenomenon in pyranoses of monosaccharides that appears to destabilize the -anomers of monosaccharides over the -anomers. • This effect arises out of the spatial electronic interaction (repulsion) between the orbitals of the lone pairs of electrons on the pyranose ring oxygen and those on the hydroxyl group at the anomeric carbon of anomeric pyranoses. 12:40 PM 9 Properties of Monosaccharides Anomeric Effect: The Electronic factor

Electronic factor • Due to the close proximity between the hemi-acetal oxygen atoms and hence their electron pairs, there is greater electronic repulsion between the lone-pair electron orbitals in the -anomer compared to those of the -anomer. • This phenomena leads to, what amounts to, a preferential stabilization of the -pyranose (axial OH) over the - pyranose (equatorial OH).

12:40 PM 10 Modified Monosaccharide Sugars Introduction • The most common monosaccharides are the aldoses, which have oxygen attached to each of the carbons. • However, the structures of many sugars differ from the

general formula Cn(H2O)n. • They are modified by: i. Deoxygenation to generate deoxysugars ii. Substitution with amino groups to generate amino sugars. • Many of such modified sugars are frequently found as constituents of biologically significant molecules such as DNA, alkaloids and antibiotics.

12:40 PM 11 Modified Monosaccharide Sugars Deoxy Sugars • Deoxy sugars lack an oxygen function at one or more of the carbons of its skeleton due to replacement of the hydroxyl groups of a monosaccharide via reduction with hydrogen. • One of the most celebrated examples of deoxy sugars is 2- deoxy-D-ribose, the sugar component of DNA.

O H O H C Deoxygenation C H OH H H H OH at C-2 H OH H OH H OH CH OH CH2OH 2 D-Ribose 2-Deoxy-D-ribose

HO HO OH O OH O H H H H H H H H H OH OH OH Exists in DNA as the 12:40 PM -furanose 12 Modified Monosaccharides Aminosugars • Another important class of substituted sugars is the amino sugars in which one of the hydroxyl groups of the monosaccharide has been replaced by an amino group.

• Such amino sugars are named as derivatives of the parent sugar with the stereochemistry at the carbon atom carrying the amino group being expressed with the amino group being regarded as equivalent to an OH of the parent sugar. 12:40 PM 14 Modified Monosaccharide Sugars Aminosugars • Some of these amino sugars are important biologically. For example, D-glucosamine is readily produced in the body, where it is a key building block for making joint cartilage. • Reduction of glucosamine production with age can lead to osteoarthritis, a disease in which cartilage in joints become stiffer and may wear away. • The pain associated with arthritis can be relieved by glucosamine supplements leading to improvement in mobility.

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