D.7: TAXOL – A CHIRAL AUXILIARY CASE STUDY (AHL)
UNDERSTANDINGS
- Taxol is a drug that is commonly used to treat several different forms of cancer.
- Taxol naturally occurs in yew trees but is now commonly synthetically produced.
- A chiral auxiliary is an optically active substance that is temporarily incorporated into an organic synthesis so that it can be
carried out asymmetrically with the selective formation of a single enantiomer.
APPLICATION AND SKILLS
- Explanation of how Taxol (paclitaxel) is obtained and used as a chemotherapeutic agent
- Description of the use of chiral auxiliaries to form the desired enantiomer.
- Explanation of the use of a polarimeter to identify enantiomers.
NATURE OF SCIENCE
- Advances in technology – many of the natural substances can now be produced in laboratories in high enough quantities to satisfy
the demand.
- Risks and problems – the demand for certain drugs has exceeded the supply of natural substances needed to synthesize these
drugs.
1. TAXOL (Paclitaxel)
USED TO TREAT
- __________________  ovarian, breast and lung
MODE OF
ADMINISTRATION
SOURCE
- injected as colourless fluid as part of ______________________ treatment
- occurs naturally in Pacific ________ tree (very small yield / environmental concerns)
- most is now obtained via semi-synthetic route or by _______________ cell fermentation
STRUCTURE
(In data booklet.)
CHALLENGE WITH
SYNTHESIS
- ________________ chiral carbons
- therefore, very large possible ____________________ and diastereomers  only ______
corresponds with Taxol itself!
ENANTIOMERS VS DIASTEREOMERS
2. USE OF CHIRAL AUXILIARIES
TRADITIONAL SYNTHESIS
(of optical active compound)
- _________________ mixture produced (i.e. 50:50 mixture of two enantiomers)
- followed by ____________________ using chromatography
- re: Taxol  very ___________ yield
SYNTHESIS USING CHIRAL
AUXILIARIES
- A chiral auxiliary is used to convert a non-chiral molecule into just the
____________ enantiomer, thus eliminating the need to ______________
enantiomers from a ___________________ mixture.
*(ENANTIOSELECTIVE
SYNTHESIS)
STEPS:
1. __________________ CHIRAL AUXILIARY - Chiral auxiliary attaches
itself to the non-chiral molecule to create the ___________________ conditions
necessary to force the reaction to follow a certain path.
(i.e. Chiral auxiliary forces attack from one side of molecule.)
2. REACT _____________ and _______________ AUXILIARY - When this
species is reacted further (and the auxiliary is then removed) only the
_____________ enantiomer results.
*Auxiliary is ___________________.
*______________ is synthesized this way.
EXAMPLE: ENANTIOSELECTIVE SYNTHESIS USING CHIRAL AUXILIARY
USING POLARIMETER (REVIEW)
- The particular enantiomer required can be distinguished from other enantiomers by using a polarimeter as it will rotate
the plane of plane-____________________ light by a fixed amount in either a __________________ or anti-clockwise
direction.
*Plane-Polarized Light Animation - https://www.youtube.com/watch?v=rbx3K1xBxVU