Stereochemistry refers to the 3-dimensional arrangement of atoms in molecules. It describes compounds that are non-superimposable mirror images of each other called enantiomers. Enantiomers have the same chemical properties except for how they interact with other chiral molecules and rotate plane-polarized light in opposite directions. The document defines several stereochemical terms and concepts including stereoisomers, asymmetric centers, and optical activity. It also provides examples of how stereochemistry impacts the biological activity and properties of important compounds like drugs and organic molecules.
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Stereochemistry refers to the 3-dimensional arrangement of atoms in molecules. It describes compounds that are non-superimposable mirror images of each other called enantiomers. Enantiomers have the same chemical properties except for how they interact with other chiral molecules and rotate plane-polarized light in opposite directions. The document defines several stereochemical terms and concepts including stereoisomers, asymmetric centers, and optical activity. It also provides examples of how stereochemistry impacts the biological activity and properties of important compounds like drugs and organic molecules.
Stereochemistry refers to the 3-dimensional arrangement of atoms in molecules. It describes compounds that are non-superimposable mirror images of each other called enantiomers. Enantiomers have the same chemical properties except for how they interact with other chiral molecules and rotate plane-polarized light in opposite directions. The document defines several stereochemical terms and concepts including stereoisomers, asymmetric centers, and optical activity. It also provides examples of how stereochemistry impacts the biological activity and properties of important compounds like drugs and organic molecules.
Copyright:
Attribution Non-Commercial (BY-NC)
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Download as PPT, PDF, TXT or read online from Scribd
Stereochemistry refers to the 3-dimensional arrangement of atoms in molecules. It describes compounds that are non-superimposable mirror images of each other called enantiomers. Enantiomers have the same chemical properties except for how they interact with other chiral molecules and rotate plane-polarized light in opposite directions. The document defines several stereochemical terms and concepts including stereoisomers, asymmetric centers, and optical activity. It also provides examples of how stereochemistry impacts the biological activity and properties of important compounds like drugs and organic molecules.
Copyright:
Attribution Non-Commercial (BY-NC)
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Download as PPT, PDF, TXT or read online from Scribd
3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned in order to fully communicate and understand the concepts.
Definitions Stereoisomers compounds with the same connectivity, different arrangement in space Enantiomers stereoisomers that are non- superimposible mirror images; only properties that differ are direction (+ or -) of optical rotation Diastereomers stereoisomers that are not mirror images; different compounds with different physical properties
More Definitions Asymmetric center sp 3 carbon with 4 different groups attached Optical activity the ability to rotate the plane of plane polarized light Chiral compound a compound that is optically active (achiral compound will not rotate light) Polarimeter device that measures the optical rotation of the chiral compound Plane-Polarized Light
Plane-Polarized Light through an Achiral Compound Plane-Polarized Light through a Chiral Compound Polarimeter Measures Optical Rotation Specific Rotation, []
[] = / cl o = observed rotation c = concentration in g/mL l = length of tube in dm
Dextrorotary designated as d or (+), clockwise rotation Levorotary designated as l or (-), counter- clockwise rotation Specific Rotations of some Common Organic Compounds Compound [o] # * centers Penicillin V +233.0 3 Sucrose +66.5 10 Camphor +44.3 2 MSG +25.5 1 Cholesterol -31.3 8 Morphine -132.0 5 Chirality Center Carbon has four different groups attached Enantiomers nonsuperimposible mirror images OH CH 3 HO 2 C H OH CO 2 H CH 3 H mirror plane (S)(+) lactic acid (R)(-) lactic acid from muscle tissue from milk [o] = +13.5 [ o] = -13.5 o o Enantiomeric Excess (Optical Purity)
actually 94.3% (+) 11.4% racemic 88.6% (+) = 88.6% e.e. x 100 123.0 109.0 e.e. = o observed rotation = +109 from oranges o [o] = +123.0 H from lemons o [o| = 123.0 (S)-(-) Limonene (R)(+) Limonene H x 100 = enantiomeric excess(e.e.) rotation of pure enantiomer observed rotation Biological Activity (R)(+) Thalidomide (S)(-) Thalidomide N N O O O O H H a sedative and hypnotic a teratogen N N O O O O H H SSRI Efficacy depends on Stereochemistry O N(CH 3 ) 2 F NC * (+/-) Celexa (-) Lexapro Absolute Configuration 1 2 3 4 Use Cahn, Ingold, Prelog priorities Place the lowest priority group back (focus down C - 4 bond) (R) clockwise draw arrow from 1-2-3 1 2 3 4 (S) counterclockwise Assign Priority to each Group on Asymmetric Center focus down C-4 bond 4 3 2 1 I Cl H F rotate I F H Cl Lactic Acid (S) (R) 4 3 2 1 4 3 2 1 OH CH 3 CO 2 H H OH CH 3 HO 2 C H C.I.P. Priorities CH 2 CH 2 CH 3 CH(CH 3 ) 2 CH 2 CH 2 OH CH 2 CH O CH 2 CH 2 CH 3 CH=CH 2 CO 2 H CH 2 Cl Low High CH 2 CH 2 Br CH(CH 3 ) 2 Fischer Projections Vertical bonds move away (dashed bonds) Horizontal bonds approach you (wedge bonds) OH CO 2 H CH 3 H OH CH 3 HO 2 C H OH CO 2 H CH 3 H Assigning Absolute Configuration to Fischer Projections OH CO 2 H CH 3 H OH CO 2 H CH 3 H OH CH 3 HO 2 C H (S) (S) (S) rotate Rotation of the Projection 90 o Reverses Absolute Configuration 90 o 90 o o 90 (S) (R) (S) (R) CH 3 H OH HO 2 C CO 2 H CH 3 H HO H OH CO 2 H CH 3 OH CO 2 H CH 3 H Diastereomers Stereoisomers That Are Not Mirror Images 3 3 2 2 opposite stereochemistry at C 3 same stereochemistry at C 2 (S) CO 2 H OH H Br H CO 2 H OH H Br H (2S,3S) (2S,3R) Fischer Projections with 2 Chiral Centers CO 2 H CH 3 H OH Br H H Br H OH CO 2 H CH 3 (2S,3S) (2S,3R) 2 3 2 3 2 Chiral Centers 4 Stereoisomers Identical, Enantiomers or Diastereomers? H H CH 3 CH 3 & CH 3 CH 3 H H C C a) CH 2 CH 3 CH 3 H H Br Br CH 2 CH 3 CH 3 & b) OH HO NH 2 NH 2 Tartaric Acids CO 2 H CO 2 H H OH HO H H OH HO H CO 2 H CO 2 H CO 2 H CO 2 H H OH H OH HO H HO H CO 2 H CO 2 H R,R S,S R,S S,R Racemic Mixture o (g/mL) 1.7598 1.7598 1.7723 m.p. C 168-170 168-170 210-212 [o] (degrees) - 12 + 12 0 (R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid Racemic Mixture (Racemate): 50/50 mixture of enantiomers CO 2 H CO 2 H H OH HO H H OH HO H CO 2 H CO 2 H R,R S,S Meso Compound Internal Plane of Symmetry Optically Inactive o rotate 180 superimposible CO 2 H CO 2 H H OH H OH HO H HO H CO 2 H CO 2 H R,S S,R mirror plane 2,3,4-trichlorohexane How many stereoisomers? Cl Cl Cl 3 asymmetric centers 8 stereoisomers * * * 2 n , n= # asymmetric centers (3) n = 3; 2 n = 8 CH 3 CH 2 CH 3 H Cl Cl H H Cl Cl H H Cl Cl H CH 3 CH 2 CH 3 CH 3 CH 2 CH 3 Cl H H Cl H Cl Cl H Cl H H Cl CH 3 CH 2 CH 3 H Cl H Cl H Cl CH 3 CH 2 CH 3 Cl H Cl H Cl H CH 3 CH 2 CH 3 Cl H H Cl H Cl CH 3 CH 2 CH 3 H Cl Cl H Cl H CH 3 CH 2 CH 3 S S R R R S A Carbohydrate CHO CH 2 OH H OH HO H H OH H OH (+) D-Glucose R S R R Internal Planes of Symmetry CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 Both are Meso Asymmetric Centers on Rings Br Br Br Br 1(R),2(S) cis 1,2-dibromocyclohexane nonsuperimposible but A flips into B A B Br Br Meso Allenes can be Chiral C C C H CH 3 C C Cl H C CH 3 H Cl H Mycomycin, an antibiotic C C C H CH=CHCH=CHCH 2 CO 2 H C C C C H H Nocardia acidophilus [o] D = -130 o Reactions that Generate Chirality Centers Hydrogenation, syn CH 3 CH 3 CH 2 CH 3 CH 2 CH 3 H 2 , Pt/C CH 2 CH 3 CH 2 CH 3 CH 3 CH 3 H H CH 2 CH 3 CH 2 CH 3 H CH 3 H CH 3 product is meso Bromination Trans is formed exclusively No Meso is formed (cis) racemic mixture S S R R Br Br Br Br Br 2 Bromonium Ion is Opened Equally from Both Sides Br 2 Br Br Br Br R R S S racemic mixture Br Br Br Br Br Br o o + - trans alkene + anti addition = MESO CH 2 CH 3 CH 2 CH 3 H H Br 2 CH 2 CH 3 CH 2 CH 3 H H Br Br Br Br CH 2 CH 3 CH 2 CH 3 H H meso cis Alkene + anti addition = racemic mixture H CH 2 CH 3 CH 2 CH 3 H Br 2 Br Br CH 2 CH 3 CH 2 CH 3 H H R R CH 2 CH 3 CH 2 CH 3 H H Br Br CH 2 CH 3 CH 2 CH 3 H H Br Br S S Br H H CH 2 CH 3 CH 2 CH 3 Br Br Br H H CH 2 CH 3 CH 2 CH 3 a b a b Brominations Often Generate Asymmetric Centers Br 2 R R S S racemic mixture CH 3 CH 3 H H CH 3 CH 3 Br Br H H CH 3 CH 3 Br Br H H CH 3 CH 3 H H CH 3 CH 3 H H Br Br CH 3 CH 3 Br Br H H S R meso Br 2 Asymmetric Center is Generated Racemic Mixture Formed H-Br H H Br Br a) b) Br H a) Br H b) (R) (S) Asymmetric Induction PPh 2 PPh 2 RuCl 2 CH 3 OH H 2 Ru(BINAP)Cl 2 CH 3 H OH 96% e.e. Noyori and Knowles shared Nobel Prize in Chemistry, 2001 Preparation of (L)-Dopa for Treatment of Parkinsons HO HO CH 2 C CO 2 H NH 2 H l-(-) Dopa HO HO CH 2 CH 2 NH 2 Dopamine cannot cross blood-brain barrier C=C NH 2 CO 2 H H HO HO H 2 Rh(DIOP)Cl 2 enz. Relevance of Stereochemistry (S,S) (R, S) useful decongenstants d-pseudoephedrine and l-ephedrine 4 stereoisomers * * 2 asymmetric centers EPHEDRA from Ma Huong NHCH 3 CH 3 OH One-step synthesis Pseudophed * d-(S)- "Meth" l-(R) - Vicks (methamphetamine) "desoxyephedrine" NHCH 3 CH 3 o-(p-isobutylphenyl)propionic acid CH 3 CO 2 H H (S)(+) ibuprofen (R)(-) ibuprofen CH 3 HO 2 C H anti-inflammatory 80-90% metabolized to (S)(+) Model of Thalidomide How Sweet it is! Sucrose O HO OH O CH 2 OH O CH 2 OH CH 2 OH HO HO OH Sucralose or Splenda O Cl HO OH O CH 2 OH O CH 2 Cl CH 2 Cl HO HO Sucralose is 600 times sweeter and does not get metabolized. Sildenafil (Viagra) and Caffeine N N N N CH 3 H O CH 3 CH 2 O S N N CH 3 O O N N N N CH 3 O O CH 3 CH 3 Radiosensitizer of Choice Until 2004 Okadaic acid 17 asymmetric centers O OH HOOC OH O H O O H H O OH H OH O O