L10/11 - Stereochemistry 2

• dextrorotatory (+)


  rotates plane polarised light to the right

  
  

  (can only tell experimentally, not by looking at a molecule)
• levorotatory (-)


  rotates plane polarised light anticlockwise, or to the left

  
  

  (can only tell experimentally, not by looking at a molecule)
• chiral vs stereogenic


  Molecules are chiral (chirality reserved for centres). Achiral molecules have no plane of symmetry

  
  

  Centres are stereogenic (steroegenic reserved for centres). A stereogenic centre has 4 different groups attached.
• Old system of assigning stereochemistry

  Used D-glyceraldehyde

  - if stereogenic centres matched, it was labelled D

  - if it didn't match, labelled L.

  
  

  (matching as in if the hydrogen in the molecule matched the stereochem of that i D-glyceraldehyde, eg thick wedge)

  
• New system of assigning stereochemistry

  CIP rules

  1. assign priorities of groups

  (double bonds count as two sigma bonds, lone pairs count as 0)

  
  

  2. Orientate the 4th group (usually H) at the back of a molecule so the other three are in the plane

  
  

  3. Follow the sequence of 1,2,3 with an arrow

  
  

  4. clockwise/right = R configuration

  anticlockwise/left = S configuration

  
• Assigning R and S centres

  Applied to centres

  
  

  - trial and error - commit to drawing one enantiomer first

  - find stereocentre

  - assign priorites and place lowest at back

  - draw arrows - clockwise = R, anticlockwise = S

  
  

  USE MODEL KIT!!!
• Re and Si faces

  Applied to faces.

  
  

  Nucleophile can add to front or back face of a carbonyl carbon. Molecule doesn't have a stereocentre and may have a plane of symmetry.

  
  

  Re = clockwise

  Si = anticlockwise after assigning CIP rules. Front and back is arbituary and assigned with stereochemistry of tetrahedral product formed after the nucleophilic addition.

  
• Racemisation


  process of making a racemic mixture
• Thalidomide

  
  

  (why do enantiomers have different properties?)

  undergoes keto-enol tautomerisation in the body

  - proton can be added to top or bottom face in keto-enol tautomerisation (Re or Si)

  - alpha carbon is stereogenic in keto form. Enol form destroyed stereocentre

  - S enantiomer = teratogenic (causes developmental malformation)

  - R enantiomer = sedative (morning sickness)

  
  

  - keto-enol tautomerisation is a form of racmeisation

  
  

  
  

  - Enantiomers have identical physical properties (except with PPL) BUT molecules are chiral and so are we... pharmacokinetics - what the body does to the drug.
• Citalopram/Escitalopram

  
  

  (Omeprazole/Esomeprazole)


  - enantiomers don't racemise, so are stable

  - sold as racemic mixture - one active, one inactive enantiomer that don't interconvert

  - chiral SSRI

  - 20mg OD

  
  

  Escitalopram:

  - JUST active S enantiomer (configuration)

  - 10mg OD

  
• Diastereomers


  stereoisomers that are not mirror images

  
  

  different compounds with different physical properties

  
  

  generated by interactions of chiral molecules with other chiral molecules can change physical properties and generate diastereomers
• Epimers


  when diastereoisomers differ only at one stereogenic centre

  
• Meso


  achiral molecule (no plane of symmetry) but with stereogenic centres