chiral catalysis for therapeutic drugs l.
Download
Skip this Video
Download Presentation
Chiral Catalysis for Therapeutic Drugs

Loading in 2 Seconds...

play fullscreen
1 / 12

Chiral Catalysis for Therapeutic Drugs - PowerPoint PPT Presentation


  • 162 Views
  • Uploaded on

Chiral Catalysis for Therapeutic Drugs. Organisms sense the chirality of bioactive compounds Carvone enantiomers bind different chiral taste and odor sensors: (S)-Carvone is a component of Dill and Caraway flavor (R)-Carvone is a component of Spearmint flavor

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Chiral Catalysis for Therapeutic Drugs' - danno


Download Now An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
chiral catalysis for therapeutic drugs
Chiral Catalysis for Therapeutic Drugs
  • Organisms sense the chirality of bioactive compounds
    • Carvone enantiomers bind different chiral taste and odor sensors:
      • (S)-Carvone is a component of Dill and Caraway flavor
      • (R)-Carvone is a component of Spearmint flavor
    • Limonene enantiomers bind different chiral taste and odor sensors:
      • (R)-Limonene is a component of Orange flavor
      • (S)-Limonene is a component of Lemon flavor
slide2

Aspartame enantiomers bind different chiral taste and odor sensors:

    • One enantiomer of Aspartame is 160 times sweeter than sugar
    • The other enatiomer tastes bitter

II. Chiral Drugs

  • Drugs are (or have been) frequently prepared as Racemic Mixtures
    • Usually, only one enantiomer is biologically active
    • The other was generally assumed to be completely inactive
  • Thalidomide is an example where the “silent” enantiomer was actually deadly
slide3

III. Origins of Chirality in Organisms

  • Several theories exist about how organisms became so stereoselective
    • Circularly polarized light is produced by some stars.
      • Differential interaction with enantiomers by polarized light
      • Destruction of one enantiomer by photoreactions results in enrichment of the other enantiomer
      • Organisms evolve in an environment containing enriched enantiomer
    • Resolution of racemic amino acids by chiral mineral faces
      • Some minerals crystallize with chiral crystal faces: CaCO3, calcite
      • Amino acids are strongly adsorbed to solid calcite
      • Evolving Organisms may have (by chance) grown on/near a certain chiral face of such a mineral where amino acids were resolved
slide4

All of our proteins are made from single enantiomer amino acids

    • Organisms only use L-amino acids

2) Organisms primarily use D-sugars

L-amino acid

D-amino acid

slide5

Chiral Transition Metal Catalysts help produce single enantiomer drugs

    • Changes in the Drug Industry
      • Currently, each enantiomer of a chiral drug must be tested and approved independently
      • Drug companies want to avoid racemic mixtures because of the added cost and potential for undesirable side effects
      • The percentage of single enantiomer drugs grew rapidly between 1989-2000
slide6

Organisms’ responses to enantiomers

    • Drug receptor sites (usually proteins) are themselves chiral
    • Chiral drugs may not be able to bind effectively to elicit the correct response
slide7

Production of a single enantiomer drug via chiral transition metal catalysts

    • Asymmetric Synthesis = production of a single enantiomer
    • Chiral ligands (“chiral auxiliary”) controls the way reactants can bind to the metal ion during a synthetic step catalyzed by the metal ion
    • The chiral auxiliary must be a pure enantiomer itself, so that only one enantiomer of the product is formed
    • Catalysts use one chiral ligand to produce (turnover) many molecules of a chiral product
    • Sharpless, Noyori, and Knowles won the 2001 Nobel Prize for this idea
slide8

Asymmetric Hydrogenation

    • Chiral ligands on hydrogenation catalysts can force interaction with only one face of a double bond during hydrogenation
    • Asymmetric Hydrogenation in the Synthesis of Naproxen
      • (S)-Naproxen is a well-known anti-inflammatory
      • (R)-Naproxen causes liver damage
      • (S)-BINAP (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) is used to make a chiral Ru catalyst (Noyori)
slide10

Rhodium Catalyzed Synthesis of L-DOPA

    • L-DOPA is used in the treatment of Parkinson’s Disease
    • D-DOPA is not active, but becomes toxic when it builds up
    • Chiral DiPAMP Ligand used to make a chiral Rh(I) Catalyst (Knowles)
    • Stereoselective Hydrogenation yields L-DOPA
slide11

Iodosobenzene

  • Asymmetric Oxidations
    • Salen Complexes for Assymetric Epoxidations
      • Chiral centers close to the metal center
      • Simple to prepare—substituted salicylaldehyde plus chiral diamine
      • Stable to oxidation; range of oxidants can be used
      • Mechanism
      • Process Scale Production of a Potassium Ion Channel Activator
slide12

Sharpless Asymmetric Epoxidation

    • Uses Titanium complex of a chiral tartrate diester
    • Catalyst Strucure is thought to be a dimer

c) Used to produce chiral intermediates for several chiral drugs