Chirality 3 & 4 Flashcards
For a compound with n asymmetric C atoms, how many possible stereoisomers is there?
2*n
What do molecules with 2 identical chiral carbons have?
2*2 theoretically possible stereoisomers BUT only 3 actual different isomers
What are meso compounds?
2 or more asymmetric C + plane of symmetry
What do chiral compounds not have?
Plane of symmetry
So what are meso compounds?
Achiral
What are meso stereoisomers?
Molecules with 2 identical chiral Cs that have 3 stereoisomers
What do meso compounds form?
R,S or S,R
Why is meso-DMSA important?
Used medically to chelate toxic metals in cases of metal poisoning
How do you identify asymmetric Cs in cyclic compounds?
Non-superimposable mirror image BUT equal energy + interconvertible
What is a stereoisomer of cyclic compounds + describe it?
1,4-dimethylcyclohexane
= neither cis or trans isomers optically active
= each has plane of symmetry
Describe 1,3dimethylcyclohexane
Trans + cis compounds each have 2 stereogenic centres
Cis compound = plane of symmetry + meso
Trans = pair of enantiomers
What the properties of diastereoisomers?
Most have same chemical reactivity
Different physical properties
How are diastereoisomers separated?
By different physical characteristics
eg. different solubility in solvents
How are diastereoisomers separated using solubility properties?
Use solvent in which one diastereoisomer is very soluble, + other not so
Both dissolve
Less soluble crystallises + filtered out
Evaporate solvent = pure other diastereoisomer
What is the resolution method?
Separation of enantiomers from either racemic mixture or enantiomerically enriched mixture
What is chiral chromatography method?
Normally HPLC or GC where racemic solution is passed over chiral stationary phase giving rapid + reversible diastereotopic interaction
How do we separate enantiomers?
Use difference in physical properties
Describe classical resolution: separation of diastereoisomers
R- acid + S-acid = enantiomers ----> R,S-salt + S,S-salt diastereoisomers ----> crystallise + separate R,S-salt + HCl ----> S-baseH+ + R-acid S,S-salt + HCl ----> S-baseH+ + S-acid
Describe resolution by esterification
R- acid + S-acid = enantiomers
—-> S-alcohol + catalytic acid
R,S-ester + S,S-ester diastereoisomers
R,S-ester (ester hydrolysis) —-> S-alcohol + R-acid
S,S-ester (ester hydrolysis) —-> S-alcohol + S-acid
How do you recover enantiomers?
Aqueous acid/ reflux (ester hydrolysis)
If there is 2 identical chiral centres with internal mirror plane in one, what is produced?
Achiral-meso form
9only 3 stereoisomers)
What are the pharmacological effects of chirality?
Appropriate recognition by targets
Strong binding to targets
Correct pharmacological activity
BUT if only 1 enantiomer active = inactive form can cause adverse effects sometimes
What are the biochemical effects of chirality?
Effects reactions involving chiral Cs
What is a stereoselective reaction?
Preferential formation of 1 stereoisomer over another
What is a stereospecific reaction?
Each stereoisomeric reactant produces a different stereoisomeric product or a different set of products
What happens chiral reactant +/or product can show no stereoselectivity?
Result in racemic mixture
What happens chiral reactant +/or product can show stereoselectivity?
Invert stereochemistry or converse stereochemistry
What are stereochemical outcomes important in?
Metabolism of drugs
Drug action at receptors
Toxicity through undesirable activity of stereoisomers
What is a concerted reaction?
Bond making + breaking happen in same step
Stereochemistry either inverted or conserved
What is an example of a concerted reaction?
Biological systems, such as enzymes
What is a non-concerted reaction?
Bond making + breaking happens in different steps
Intermediates are formed
Racemisation if intermediate formed
What do intermediates allow?
Changes to stereochemistry
What are happens in concerted SN2 reactions?
Happen at sp3 C
Polarised bond between C + heteroatom = makes it E+
Nu- attacks electrophilic C = breaks bond as new bond is made = 1 step
No intermediate formed
1 product
What happens in concerted reactions involving 2 chiral centre formation?
Only cis isomers obtained with alkenes containing fewer than 8 ring atoms
What happens in non-concerted SN1 reactions?
Happen at sp3 C Polarised bond between C + heteroatom breaks Intermediate carbocation formed Stereochemical definition lost Reactants form new bond to C Attack planar intermediate from above + below the plane 1:1 mix of enantiomers NO stereoselectivity
Describe non-concerted electrophilic addition - alkenes
Occur at sp2 carbocations
More than 1 step
Intermediate carbocation or radical formed = planar
What is syn?
Two substituents added to same side of double bond
What is anti?
Two substituents added to opposite sides of double bond
