Stereochemistry 2

• What are diastereoisomers?

  Stereoisomers that are not mirror images

  
• How do enantiomers differ from diastereoisomers?

  Enantiomers are mirror images; diastereoisomers are not

  
• What is an epimer?

  Isomers differing at one chiral centre
• What is the formula for the maximum number of isomers based on chiral centres?

  2$^n$ where n is the number of chiral centres
• What is the relationship between diastereoisomers and enantiomers?

  • Diastereoisomers are not mirror images.
  • Enantiomers are mirror images and non-superimposable.
  • Diastereoisomers can have different physical properties.

  
• How many chiral centres are in the example provided?

  9 chiral centres
• What is a meso form?

  An isomer with an internal plane of symmetry
• How many stereoisomers does tartaric acid have?

  3 stereoisomers
• What are the properties that differ between diastereoisomers?

  • Solubility
  • Boiling point
  • Melting point
  • NMR
• How can diastereoisomers be separated?

  By chemical and physical methods
• What is the purpose of a resolving agent in separating enantiomers?

  To create diastereoisomers for separation
• What is a racemic mixture?

  • A 50:50 mixture of two enantiomers.
  • Does not rotate plane-polarized light.
  • Requires separation to obtain pure enantiomers.
• What are the basic steps to separate enantiomers by converting to diastereoisomers?

  1. React with a pure chiral reagent.
  2. Separate the resulting diastereoisomers.
  3. Cleave and separate the enantiomers.
• Why is simple chromatography ineffective for separating enantiomers?

  Enantiomers have similar physical properties
• Which atoms can be chiral centres besides carbon?

  Nitrogen, silicon, phosphorus, sulphur
• What happens to ethylmethylamine regarding its enantiomers?

  It undergoes rapid umbrella-like inversion
• What is the significance of chirality in drug development?

  It influences drug absorption and metabolism
• What factors should be considered when choosing between a racemate and a pure enantiomer for drugs?

  • Pharmacological activity
  • Toxicity differences
  • Metabolism differences
  • Developmental costs
  • Clinical trial results
• What is a racemic switch in drug development?

  Developing single enantiomers from racemates
• What are the considerations for a racemic switch?

  • Chemical feasibility
  • Clinical advantages
  • Marketing advantages
• What guidelines did the European Medicines Agency adopt in 1994?

  • Investigation of chiral active substances.
  • Suitable toxicity testing for racemates.
  • Characterization of starting materials and products.
• What can happen to an enantiomerically pure compound in vivo?

  It may undergo partial or complete racemization
• What is the effect of the R stereoisomer of ibuprofen in vivo?

  63% converts to the S form
• Why is it essential to document drug stereochemistry?

  • To understand pharmacokinetics.
  • To track interconversion of enantiomers.
  • To ensure safety and efficacy in trials.