D7 taxol: a chiral auxillary case study

Question 1

what is optical isomerism

Answer 1

chiral drugs exists in 2 forms w diff activities

Same molecular and structural formula BUT cannot be superimposed

Question 2

what is a racemic mixture

Answer 2

a mixture containing diff enantiomers
- pharmaceutical comps need to id harmful ones bc only 1 is desired

Question 3

after what event are racemic mixtures carefully picked

Answer 3

thalidomide tragedy
- only 1 isomer had desired resutls: sleep in pregnant women
- its enantiomer caused serious deformities in the foetus

Question 4

what is taxol (short)

Answer 4

an anti cancer drug

Question 5

how does taxol stop cancer 4

Answer 5

1. microtubules in cells form spindles during cell div
2. main componenet of microtubules is tubulin
3. taxol binds to tubulin = prevents spindle fibres from breaking down
4. stops cell div = stops tumour growth

Question 6

natural source of taxol

Answer 6

pacific yew trees, discovered 1970s

Question 7

environmental concerns abt using pacfic yew trees as taxol source 2

Answer 7

• yew bark has very small amt of taxol = high amt of bark required
• stripping bark kills the tree – requires 200y to mature

Question 8

challanges in designing the synthesis of taxol

Answer 8

• taxol is ‘very chiral’, has 11 chiral carbon centres
• only 1 enantiomer has desired activity, but process of isolation is wasteful

Question 9

what is enantioselective synthesis / aysmmetric synthesis

Answer 9

way to directly synthesize a single enantiomer

Question 10

how can enantiomers be identified

Answer 10

using a polarimeter that measures the rotation of plane-polarized light by the optically active compound using an analyser

Question 11

what future research is there for taxol

Answer 11

• taxol produced by some fungis fermentation reactions
• taxol extracted from plant cell cultures and purified via chromatography

Question 12

one way to go about enantioselective synthesis is through using the ____ _______

Answer 12

chiral auxillary

Question 13

because taxol is a complex molecule, commerical synthesis requires ___ steps and has ___ yield

Answer 13

30
poor

Question 14

how is the chiral auxillary used to achive asymmetric synthesis/ enantioselective synthesis 4

Answer 14

1. thru use of steric hindrance,
2. chiral molecule binds to reactant = physically blocking out one reaction site
3. ensures reaction will proceed with specified stereochemistry
4. auxillary taken off and recycled after reaction ceases

Question 15

example of asymmetric synthesis / enantioselective synthesis

Answer 15

converting propanoic acid (non-chiral) into 2-aminopropanoic acid (Chiral)
- with chiral auxillary: both enantiomers prod
- with chiral auxillary: only one enantiomer prod

Question 16

2 strategies of syntehsising a single enantiomer

Answer 16

1. using chiral auxillary
2. semi-synthetic synthesis

Question 17

what does semi-synthetic synthesis involve

Answer 17

the extraction of a compound that is related to taxol from the needles and leaves of yew trees
- precursor from nature = name
- harvesting leaves doesnt damage tree

Question 18

what compound is found in needles and leaves of yew trees that is chemically modified to procude taxol

Answer 18

10-DAB

Question 19

concerns abt 10-DAB conversion to taxol

Answer 19

requires 13 solvents + range of other organic reagents
- large no of steps = little yield