Kloramfenikol

2,2-dichloro-N-((1R,2R)-1,3-dihydroxy-1-(4nitrophenyl)propan-2-yl)acetamide

 Cis/Trans 1,2 dikloro etena

Cis/trans 1,2 dikarboksilat etena

How Sweet it is!

OH HO OH O CH2OH O CH2OH O HO CH2OH HO Sucralose or Splenda Cl HO OH O CH2OH O CH2Cl O HO CH2Cl

HO Sucrose

Sucralose is 600 times sweeter and does not get metabolized.

Stereochemistry
Stereochemistry refers to the 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.

Structural/Constitusional Isomers
1. a)
CH3 CH2 CH2 CH3

CH3

Butane (C4H10)
2.

CH3 CH CH3 2-methylpropane (C4H10)

CH3 CH CH CH3

CH2 CH CH2 CH3

1-butene

2-butene

CH3 CH2 C CH3

CH2 CH2 CH2 CH2

CH2 CH2 CH

2-methylpropene

cyclobutane methylcyclopropane

CH3

Definitions
Stereoisomers compounds with the same connectivity, different arrangement in space Enantiomers stereoisomers that are nonsuperimposible 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 sp3 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

Lingkup Stereoisomer
Isomer Konformasi : single bond rotated Isomer Konfigurasi
Isomer Geometri : cis/trans ; E/Z Isomer Optik :
Enantiomer : +/- ; d/l ; R/S, Disstereomer

Isomer Konformasi (konformer)

Konformasi : perubahan bentuk molekul dalam ruang oleh karena adanya putaran (rotasi) pada ikatan tunggal (single bond) Konformasi senyawa terjadi pada : a. Senyawa rantai terbuka (alifatis) b. Senyawa rantai tertutup (siklis)

Konformasi Senyawa Alifatis

Etana : CH3-----CH3 Konformer Eklips/Gerhana Konformer Goyang/Gauche

Eklips/Gerhana
-Atom Hidrogen (atau gugus) saling menutup - Energi tinggi karena banyak terjadi tolakan antar atom

Goyang/Gauche
-Atom Hidrogen (atau gugus) tidak saling menutup - Energi rendah karena sedikit terjadi tolakan antar atom

Interchangeable
Konformer Eklips
Konformer Goyang

Konformer senyawa Butana

Konformer Goyang/Gauche Konformer Eklips/Gerhana Konformer Anti Konformer metil tereklipskan (lihat : model molekul hyperchem)

Konformer pada senyawa siklik : Sikloheksana

Konformer Kursi Konformer Setengah Kursi Konformer Biduk Belit Konformer Perahu / Biduk (lihat : model molekul hyperchem)

Konformer Kursi

Konformer Biduk

Konformer Biduk Belit

Isomer geometri
Terjadi pada :
Senyawa dg ikatan rangkap : alkena Senyawa siklik Terbentuk karena ikatan rangkap rigid/kaku Tidak dapat ber-rotasi Tidak dapat diubah satu sama lain Ada 2 posisi relatif : Bersisian = cis ; Berseberangan = trans

Contoh

Cis 1,2 dikloroetena

Trans 1,2 dikloroetena

How about this ? I Br

Aturan Chan Inglod Prelog

Urutan deret ditentukan berdasar nomor atom (no atom tinggi lebih berprioritas) Isotop dengan no massa tinggi berprioritas Jika atom sama/identik, no atom dari atom berikutnya digunakan sebagai dasar prioritas Atom-atom dengan ikatan rangkap atau ganda tiga diberi kesetaraan dengan ikatan tunggal

Isomer Geometri pada senyawa siklis

Isomer Optik
Gliseraldehid
CHO HO H CH2OH (-) Gliseraldehid H CHO OH CH2OH (+) Gliseraldehid

() = - 8,7

() = 8,7

Plane-Polarized Light

Plane-Polarized Light through an Achiral Compound

Plane-Polarized Light through a Chiral Compound

Polarimeter Measures Optical Rotation

Specific Rotation, []
[] = / cl
a = 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 (-), counterclockwise rotation

Kiralitas

Chirality Center
Carbon has four different groups attached

Enantiomers
nonsuperimposible mirror images
mirror plane OH H HO 2C CH3 CH3 OH H CO 2H

(S)(+) lactic acid

(R)(-) lactic acid

from muscle tissue from milk o o [a] = +13.5 a [] = -13.5

Biological Activity
(R)(+) Thalidomide
O
H

(S)(-) Thalidomide
O O H
N

O N

O N

H O

N O a sedative and hypnotic

O a teratogen

a-(p-isobutylphenyl)propionic acid

CH3

H CO 2H

H HO 2C

CH3

(S)(+) ibuprofen anti-inflammatory

(R)(-) ibuprofen 80-90% metabolized to (S)(+)

SSRI Efficacy depends on Stereochemistry

NC O * N(CH3)2 (+/-) Celexa (-) Lexapro F

Absolute Configuration
Use Cahn, Ingold, Prelog priorities Place the lowest priority group back (focus down C - 4 bond) draw arrow from 1-2-3 1 1 clockwise counterclockwise 4 4 2 2 3 3 (R) (S)

Assign Priority to each Group on Asymmetric Center

I Cl H F rotate
4

I H F3

Cl

focus down C-4 bond

Lactic Acid
1 OH 4 H HO2C 2 CH3 3 (S) CH3 3 (R) 1 OH H CO2H 2 4

C.I.P. Priorities
Low CH2CH2CH3 CH2CH2OH CH2CH2CH3 CO2H CH2CH2Br High CH(CH 3)2 O CH 2CH CH=CH 2 CH 2Cl CH(CH 3)2

Diastereomers
Stereoisomers That Are Not Mirror Images

H OH
3 2

H OH
3 2

CO2H

CO2H

Br H H Br (2S,3S) (2S,3R) same stereochemistry at C 2 (S) opposite stereochemistry at C 3

Fischer Projections with 2 Chiral Centers

CO2H H Br
2

CO2H H H
2

OH H

OH Br

CH3 (2S,3S)

CH3 (2S,3R)

2 Chiral Centers 4 Stereoisomers

Tartaric Acids
R,R CO2H H HO OH H CO2H R,S CO2H H H OH OH CO2H HO HO HO H S,S CO2H H OH CO2H S,R CO2H H H CO2H

Racemic Mixture
R,R CO2H H HO OH H CO2H HO H S,S CO2H H OH CO2H

Racemic Mixture (Racemate): 50/50 mixture of enantiomers

o

m.p. C (g/mL)

(R,R) Tartaric acid 168-170 - 12 1.7598

(S,S) Tartaric Acid (+/-) Tartaric acid 168-170 210-212 + 12 1.7598 0 1.7723

[a] (degrees)

Meso Compound
Internal Plane of Symmetry Optically Inactive
R,S CO2H mirror plane H H OH OH CO2H HO HO S,R CO2H H H CO2H rotate 180 superimposible
o

2,3,4-trichlorohexane How many stereoisomers?

Cl * * *

Cl Cl 3 asymmetric centers 2n, n= # asymmetric centers (3) 8 stereoisomers

n = 3;
CH3 S H S H RH Cl Cl Cl CH2CH3 CH3 H Cl H Cl H Cl CH2CH3 Cl H Cl Cl Cl Cl CH3 H R H R H S CH2CH3 CH3 H Cl H CH2CH3

n 2

=8
CH3 CH3 Cl Cl H H H Cl CH2CH3 CH3 H Cl Cl Cl H H CH2CH3 Cl Cl H CH2CH3 CH3

H H Cl

Cl H H

H Cl Cl CH2CH3

A Carbohydrate
CHO H HO H H OH H OH OH CH2OH (+) D-Glucose R S R R

Internal Planes of Symmetry

Both are Meso CH3 CH3 CH3 CH3

CH3

CH3

CH3

CH3

Identical, Enantiomers or Diastereomers?

H a) Br CH3 CH2CH3 & H Br CH2CH3 CH3

b)

HO H C CH3 C

H CH3 NH2

CH3 & H H NH2 OH CH3

Reactions that Generate Chirality Centers

Hydrogenation, syn
CH3 CH2CH3 CH3 CH2CH3 H2, Pt/C H CH3 CH2CH3 H CH3 CH2CH3

CH2CH3 product is meso H H CH3 CH3 CH2CH3

Bromination Trans is formed exclusively

No Meso is formed (cis)
Br 2 Br R R Br Br S S racemic mixture Br

Bromonium Ion is Opened Equally from Both Sides

Br 2 + Br Br Br Br R R Br Br S S

racemic mixture

Br

Br

Br

Br

trans alkene + anti addition = MESO

CH2CH3 H H CH2CH3 CH2CH3 H Br Br H CH2CH3

Br 2

CH2CH3 H meso Br

CH2CH3 H Br

cis Alkene + anti addition = racemic mixture

Br CH2CH3 H a CH2CH3 H CH2CH3 H CH2CH3 H Br 2 Br Br CH2CH3 H b Br Br

CH2CH3 H Br b CH2CH3 H
S S

CH2CH3 CH2CH3 H H a H HCH CH 2 3 CH CH 2 3

R R

CH2CH3 H Br

Br

Br

Br

Brominations Often Generate Asymmetric Centers

CH3 H CH3 H Br 2 CH3 H Br S S CH3 CH3 H Br H Br CH3 H Br R R

racemic mixture CH3 H Br Br H CH3 CH3 H Br CH3 H Br S R meso

CH3 H

H CH3

Br 2

Asymmetric Center is Generated Racemic Mixture Formed

Br H-Br a) (R) H Br a) H H H

Br b) (S)

Br

b)

Asymmetric Induction
PPh2 RuCl2 PPh2

CH3 H2 OH Ru(BINAP)Cl2

CH3 OH

96% e.e.

Noyori and Knowles shared Nobel Prize in Chemistry, 2001

Preparation of (L)-Dopa for Treatment of Parkinsons

HO HO C=C H CO2H H2 Rh(DIOP)Cl2 CO2H HO HO CH2C H NH2 enz. HO HO Dopamine cannot cross blood-brain barrier CH2CH2NH2 NH2

l-(-) Dopa

Relevance of Stereochemistry
EPHEDRA from Ma Huong
OH * * NHCH3 d-pseudoephedrine and l-ephedrine (R, S) (S, S) useful decongenstants

CH3 2 asymmetric centers 4 stereoisomers

One-step synthesis
Pseudophed

NHCH3

CH3

"desoxyephedrine" (methamphetamine) l-(R) - Vicks d-(S)- "Meth"

Model of Thalidomide

Sildenafil (Viagra) and Caffeine

CH3 O H N CH3CH2O N O N N CH3 O N N CH3 CH3 N N

O N N CH3

Radiosensitizer of Choice Until 2004

H OH O H O H O OH

HOOC OH

O O OH H O

Okadaic acid
17 asymmetric centers