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Light waves. Light can be considered as a series of transverse waves , oscillating at 90 ° to the direction the light is moving. Transverse waves can be modelled by moving one end of a Slinky up and down. direction of wave propagation. Polarized light. Optically active compounds.
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Light waves Light can be considered as a series of transverse waves, oscillating at 90° to the direction the light is moving. Transverse waves can be modelled by moving one end of a Slinky up and down. direction of wavepropagation
Optically active compounds Optically active compounds have the ability to rotate the plane of polarized light. Optically active compounds exist as two isomers, known as enantiomers. One rotates the plane of polarized light clockwise: the + or d isomer. The other rotates the plane of polarized light anticlockwise: the - or l enantiomer. d enantiomer l enantiomer polarized light
Chiral carbon atoms For a compound to be optically active it must contain a carbon atom to which four different groups are attached. Such a carbon atom is called a chiral carbon, and is denoted by a *. glycine alanine The amino acid glycine does not contain a chiral carbon whereas alanine does. Alanine would be therefore be optically active but glycine would not.
Mirror images If a chiral compound is drawn in 3D it is possible to see how the two enantiomers are different: optical isomers of alanine The two enantiomers are mirror images of each other. No matter how you rotate the molecules, it is impossible to superimpose them on top of each other.
Properties of optical isomers Optical isomers have identical physical and chemical properties, but their biological activity may be different due to the shape specificity of biological receptors. For example, limonene is an optically active compound. The d isomer is found in the peel of citrus fruit and has an orange smell. The l isomer is found in pine needles and cones and has a refreshing pine-like smell. l-limonene d-limonene Smell receptors in our nose are able to distinguish between the two different isomers.
Optically active amino acids Other than glycine, alpha amino acids are all optically active because they contain a chiral carbon. There are therefore two possible isomers of all the optically active amino acids. Usually, only one type of optical isomer is produced by an organism. In general, only the l-isomers of amino acids occur in nature. d-isomer l-isomer
Optical isomers in drug manufacture If a drug is optically active, different enantiomers may bind differently (or not at all) to target receptors in the body. One enantiomer can have a desired effect, while the other may have either no effect at all, or a different effect entirely. A racemicmixture is often used in drug manufacture because it is difficult and expensive to separate the two isomers. For example, ibuprofen is optically active. Only d-ibuprofen is pharmaceutically active, but l-ibuprofen is not harmful so ibuprofen tablets contain a racemic mixture of the two enantiomers.
Thalidomide and optical isomerism Thalidomide was used as a tranquilizer and painkiller in the 1950s. It was sold as a ‘wonder drug’ also effective at reducing morning sickness, and was prescribed to pregnant women. The birth of a large number of babies with severe birth defects was subsequently linked to thalidomide use during pregnancy. This is because thalidomide is racemic drug. The d-enantiomer is effective against morning sickness, but the l-enantiomer is teratogenic (causes birth defects). d-thalidomide l-thalidomide
Separating optical isomers When optically active substances are made in the lab, the usual result is a racemic (50:50) mixture of the two different enantiomers. If one enantiomer is harmful, or causes unpleasant side effects, the different optical isomers must be separated. This is difficult to achieve as the enantiomers have identical chemical and physical properties. Separating optical isomers is therefore time-consuming and expensive, but can improve pharmacological activity.
Obtaining optically pure compounds Optically pure compounds can be obtained from some racemic mixtures with biological methods. These natural pathways involve microorganisms and promote stereoselectivity. For example, lactic acid is found in milk and can be preparedin the lab, but in both cases a racemic mixture is the result.d-lactic acid is found in muscle but pure l-lactic acid does not occur naturally and must be obtained from the racemic mixture. This can be done with the mould Penicillium glaucum, used to make blue cheese. Given a racemic mixture, the mould feeds only on d-lactic acid, leaving pure l-lactic acid behind.
Synthesizing optically pure compounds An alternative to separation is to synthesize an optically pure product. This has the advantage that no separation is required. For example, a group can be attached to the starting material that physically blocks one of the approaches the other reagent can make, so only one enantiomer is formed. Another approach is to use naturally-occurringchiral molecules – for example l-amino acids or sugars – as the starting point for synthesis. This technique is sometimes known as chiral pool synthesis, as it makes use of a ‘pool’ of optically-pure reactants to ensure that only one type of optical isomer is present in the products.
Chiral catalysts An alternative method is the use of a chiral catalyst. Chiral catalysts transfer their chirality to reactants so that only a single type of isomer is synthesized. Examples of chiral catalysts include transition metal complexes prepared using chiral ligands, chiral organic compounds and biological molecules such as enzymes. In 1968, William Knowles created one of the first chiral catalysts from a transition metal complex. He used this technique to synthesize L-DOPA, a treatment for Parkinson’s disease.
Importance of organic synthesis Chemists are able to construct synthetic pathways to prepare a desired compound. They design a molecule and then work out how to make it from readily available precursors. This is of particular use in the pharmaceutical industry, where a molecule can be designed to have specific functional properties. A series of reactions is worked out in which each stage modifies the starting compound in a particular way; for example, adding a functional group. It is vital for each stage in the synthesis to be carried out under the right conditions.
Multiple functional groups Some compounds, for example paracetamol, contain more than one functional group. N-substituted amide phenyl hydroxyl The chemical reactivity of each functional group is usually the same as it would be on its own.
Devising a synthetic route (1/2) 1. Write down the possible products that can be made from the starting material in one step. 2. Write down the possible chemicals that can synthesize the desired product in one step. 3. Identify possible synthetic pathways. For example, synthesizing ethylamine from ethanol: CH3CHO CH3CH2CN CH3CH2NH2 CH3CH2OH CH3COOH CH3CH2Cl CH3CH2Cl CH3CH2OOR
Devising a synthetic route (2/2) Synthesis of propanoic acid (CH3CH2COOH) from ethyl chloride (CH3CH2Cl): 1. Write down the possible products that can be made from the starting material in one step. As the carbon chain increases in length the reaction must be via a nitrile. CH3CH2COOH CH2CH2 2. Write down possible products from the nitrile. CH3CH2CN CH3CH2Cl CH3CH2CH2NH2 3. Identify possible synthetic pathways. CH3CH2NH2 CH3CH2OH
