Transcript D7 Taxol® * a chiral auxiliary case study (HL)
Option D HL When a molecule contains a carbon atom bonded to four different groups, it is said to be chiral and two mirror images (known as enantiomers) exist. These enantiomers can behave very differently in the body as a result of their different shapes. E.g. one enantiomer can combine with a specific protein because its functional groups are in correct position. Developed in Germany in the 1953. Used as a tranquilizer (19571962). Prescribed to combat morning sickness in the early months of pregnancy. Marketed widely in Europe but never approved by the FDA in the USA. Caused major birth defects in ABOUT 10,000 children whose mothers had taken thalidomide. 3 Thalidomide has two optical isomers, one of which is a powerful teratogen. Chiral Carbon 4 Thalidomide is both a tranquilizer and a teratogen It is sometimes used to treat some symptoms of Hansen’s disease. (Leprosy) 5 Many drug with chiral center are synthesized from materials that have no chiral center. The product is racemic mixture. To obtain single enantiomer chiral auxiliary center is used. A chiral auxiliary is one enantiomer of an optically active substance that is temporarily incorporated into a non-chiral molecule to produce a single enantiomer of a product in an organic synthesis reaction. Chiral auxiliary allows reagent to approach from the one side of the molecule, so forcing the reaction to produce only one type of enantiomer. Once reaction is complete chiral auxiliary is removed Chiral auxiliaries are successfully used in semi-synthesis of anticancer drug Paclitaxel (Taxol). Paclitaxel is used to treat several forms of cancer – mainly breast, ovarian and lung cancer. It is usually given intravenously as part of a course of chemotherapy to treat cancer. Paclitaxel acts by preventing cell division – it does this by binding to microtubules in the cytoplasm, preventing them from breaking down during cell division. Paclitaxel was originally obtained from Pacific yew tree bark – however, it took the bark from more than one tree to provide enough paclitaxel to treat just one patient and so semi-synthetic processes were developed that involved making paclitaxel from another natural product derived from the needles of yew trees. Semi-synthesis of the drug allowed it to be made on a larger scale and reduced the environmental impact – extracting the drug from its natural source results in killing of the trees. Nowadays paclitaxel is also made by fermentation using plant cell cultures. Optically active enantiomers can be distinguished using polarimeter, because they rotate plane polarized light in opposite directions A simple polarimeter consists of a source of light (usually a sodium lamp producing one specific wavelength), two polarising filters, a sample tube and a scale to measure the degree of rotation of the plane-polarised light An enantiomer that rotates plane-polarised light clockwise (to the right – dextrorotatory) is called the (+)-enantiomer and one that rotates the plane anticlockwise (to the left – levorotatory) is called the (−)-enantiomer. An enantiomer can be identified from its specific rotation. The specific rotation, [α], is worked out from the angle though which the plane-polarised light is rotated in degrees (α), the path length of solution that the light passes through (l) in dm and the concentration of the solution (c) in g/cm−3:. Science is both systematic and creative. Systematic screening of a large number of plant extracts identified paclitaxel as a possible anticancer drug. When the demand for paclitaxel exceeded the supply from natural sources scientists had to develop ways of making this important drug. A great deal of creativity was involved in designing ways of making paclitaxel.