1 / 30

Pharmaceutical Organic Chemistry

Pharmaceutical Organic Chemistry. Lec 3. Stereochemistry. Optical isomerism. Absolute Configuration ( AC ). Is the actual spatial arrangement of atoms or groups around a chiral carbon. In 1891 German chemist [ Emil Fisher ] introduce formula showing the spatial arrangement ……….

robert-contreras
Download Presentation

Pharmaceutical Organic Chemistry

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. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Pharmaceutical OrganicChemistry Lec 3

  2. Stereochemistry Optical isomerism Absolute Configuration ( AC ) Is the actual spatial arrangement of atoms or groups around a chiral carbon In 1891 German chemist [ Emil Fisher ] introduce formula showing the spatial arrangement ………

  3. configuration– the arrangement in space of the four different groups about a chiral center. How do we show configurations? “wedge” formulas Fischer projections “cross structures” use only for chiral centers!

  4. Rules for Fischer projections • Arrange the molecule so that horizontal bonds at chiral carbon point toward you and vertical bonds point away from you.

  5. H • Br • Cl • F • Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back.

  6. Stereochemistry Optical isomerism (±)- Ethanolamine CH3CH(OH)NH2 has one chiral carbon, so 2- enantiomers H H H2N OH H2N OH CH3 CH3 Mirror Fischer projection formula

  7. Determination of ( AC ) by ( R ) and ( S ) system Groups are assigned a priority ranking using the same set of rules as are used in ( E ) and ( Z ) system CH3CH(OH)NH2 1. Draw Fischer Projection formula H OH H2N CH3

  8. Determination of ( AC ) by ( R ) and ( S ) system Groups are assigned a priority ranking using the same set of rules as are used in ( E ) and ( Z ) system CH3CH(OH)NH2 2. Rank the substitution according to the priority order H OH > NH2 > CH3 > H OH H2N 1 2 3 CH3

  9. Determination of ( AC ) by ( R ) and ( S ) system 3. The group (atom) with lowest priority [H] should be away from the observer , if not do an even number of changes to get H away from the observer H H2N H2N 1 OH H2N H OH CH3 OH 2 CH3 H CH3

  10. Determination of ( AC ) by ( R ) and ( S ) system 4. Draw an arrow from group with highest priority ( OH ) to second highest priority ( NH2 ) . if the arrow is …… a- clockwise, the configuration is R b- anti-clockwise, the configuration S NH2 HO CH3 (R)-ethanolamine (+)- ethanolamine H

  11. The viewing rule

  12. Switching Substituents on a Fischer Projection • Any single (odd #) exchange of 2 substituents gives the other enantiomer • Any two (even #) of exchanges gives the same enantiomer • R • S R

  13. Draw the formulas for the two enantiomers of each of the following compunds then assign each as R or S

  14. a) Analyzecompounds A, B, and C. Whichareidentical Whichareenantiomers

  15. b) Howarethefollowingpairsofcompoundsrelated

  16. Stereochemistry (±)- CH3CH(Cl)CH(Br)NH2 n = 2 ….. So No. of stereoisomer 4 1,3 and 1,4 2,3 and 2,4 are diastereoisomers

  17. Stereochemistry Determination of ( AC ) in enatiomer 1 a. At C1 : Br > NH2 > C2 > H Br C2 2 Br NH2 C2 H 1 NH2 H AC at C1 is S

  18. Stereochemistry Stereochemistry Optical isomerism Optical isomerism Determination of ( AC ) in enatiomer 1 a. At C2 : Cl > C1 > CH3 > H C1 CH3 2 Cl CH3 Cl H 1 C1 H AC at C2 is S

  19. Enantiomers and diastereomers:EXAMPLE:2-Bromo-3-chlorobutane

  20. Meso compounds • In the simplest case, they are compounds which have internal plan of symmetry. • EXAMPLE: • Tartaric acid

  21. Stereochemistry Optical isomerism COOHCH(OH)CH(OH)COOH tartaric acid Meso-compound are : - superimposable mirror images - only 3 stereoisomers - optically inactive

  22. Racemic Mixture

  23. A racemic mixture dose not rotate the plane ofpolarization of plane-polarized light because therotation by each enantiomer is cancelledby the equal and opposite rotation by the other. • A solution of either a racemic mixture or ofachiral compound said to be optically inactive • Many drugs are optically active, with one enantiomer only having the beneficial effect. • In the case of some drugs, the other enantiomer can even be harmful, e.g. thalidomide.

  24. In the 1960’s thalidomide was given to pregnant women to reduce the effects of morning sickness. • This led to many disabilities in babies and early deaths in many cases.

  25. Thalidomide was banned worldwide when the effects were discovered. • However, it is starting to be used again to treat leprosy and HIV. • Its use is restricted though and patients have to have a pregnancy test first (women!) and use two forms of contraception.

  26. Stereochemistry Resolution of racemic mixture 1- treat the mixture with microorganism 2- using chiral reagent ( R) RCOOH ( R) RCOO- (S) R’NH3+ + ( S) R’NH2 ( S) RCOOH ( S) RCOO- (S) R’NH3+

  27. Resolution of Enantiomers React a racemic mixture with a chiral compound to form diastereomers, which can be separated. =>

  28. Examine the following structural formulas and select those that are chiral.

More Related