Download Organic Chemistry and Medicine

Organic Chemistry and Medicine
A Sample Lecture from an Organic Chemistry Course
Designed for Pre-Med, Nursing, and BiologyStudents
Jason Dinsmore, Ph.D
Facebook.com/OrganicChemistOnCall
Design of Course
A Few Common Observations…
Organic chemistry is typically taught from a chemical point of view
Organic chemistry is the one course EVERYONE has heard of and many DREAD taking
Organic chemistry is usually a “make it or break it” class for pre-med students
Does it have to be this way?
ABSOLUTELY NOT!!!
You can learn the same material that has been taught semester after semester at
universities around the world but from a medical/biological point of view
Organic Chemistry and Medicine
Or·gan·ic \ȯr-ˈga-nik\ adj : 1. of, relating to, or arising in a bodily organ; 2. of, relating
to, or containing carbon compounds; 3. relating to, being,
or dealt with by a branch of chemistry concerned with the
carbon compounds of living beings and most other carbon
compounds
Chem·is·try \ˈke-mə-strē\ n : a science that deals with the composition, structure, and
properties of substances and with the transformations that
they undergo
Med·i·cine \ˈme-də-sən\ n : 1. a substance or preparation used in treating disease; 2.
the science and art dealing with the maintenance of health
and the prevention, alleviation, or cure of disease
Organic Chemistry and Medicine
MEDICINE
ORGANIC CHEMISTRY
History and Physical Exam
Review Literature
Differential Diagnosis
Synthetic Strategy
Order labs and Procedures
Run Model Reactions
Diagnose and Treat
Synthesize Molecule
Organic Chemistry and Medicine
The format of the lectures will be as follows:
Presentation of Case Study
- Ex. 24 year old female presents to the ED with…
Discuss Functional Group(s)/Reaction(s)
- How this functional group/reaction(s) relates to the disease
Organic Chemistry and Medicine
Medicine
Organic Chemistry and Medicine
Biology
Organic Chemistry and Medicine
Organic Chemistry
Organic Chemistry and Medicine
Medicine
Organic Chemistry
Case 1
A 30-year-old man is evaluated in the emergency department for complications of
difficulty breathing, chills, and chest pain for the past 24 hours. He denies any previous
history of medical problems. On physical examination, he appears ill. His temperature is
40°C (104°F), his blood pressure is 90/50 mm Hg, and his heart rate is 110/min. Cardiac
examination reveals a 3/6 diastolic murmur; however, the patient denies any history of
a murmur. ECG results are normal.
Diagnosis: Acute Endocarditis
How does this case relate to organic chemistry?
Treatment of Endocarditis
PENICILLIN
CEFTRIAXONE
VANCOMYCIN
AMPICILLIN
GENTAMICIN
NAFCILLIN
OXACILLIN
Penicillin
R
H
N
O
O
S
N
O
OH
b-lactam structure is involved in the mechanism of action
Penicillin Mechanism of Action
Penicillin Binding Protein
- PBPs are all involved in the final stages of the synthesis of peptidoglycan,
which is the major component of bacterial cell walls.
- Bacterial cell wall synthesis is essential to growth, cell division (thus
reproduction) and maintaining the cellular structure in bacteria.
- Inhibition of PBPs leads to irregularities in cell wall structure such as
elongation, lesions, loss of selective permeability, and eventual cell death
and lysis.
Penicillin Mechanism of Action
H2N
H
N
R
O
OH
S
O
N
O
OH
O
H
H
N
N
O
O
R
R
H
H
N
N
O
O
OH
OH
R
R
S
S
OH
OH
Ser
Ser
NH
NH
SS
O
O
O
O
N
N
O
OO
O
O
O
O
O
R
R
H
H
N
N
O
O
N
N
OH
O
O
OH
OH
Ser
Ser
Nucleophilic Attack on the Cyclic Amide Carbonyl Carbon
SS
HN
HN
O
O
O
O
OH
OH
The Chemistry of Amides
R
R
O
O
O
O
H
H
R
R
H
H
N
N
O
O
H
H
O
O
NH
NH
O
O
O
O
S
S
N
N
O
O
OH
OH
Ser
Ser
S
S
HN
HN
O
O
O
O
OH
OH
NH22
NH
O
O
Biology sets the reaction up perfectly; however, this is not the
case in a chemistry laboratory….
The Chemistry of Amides
R
R
H
H
N
N
O
O
O
O
S
S
N
N
O
O
OH
OH
O
O
O
R
Cl
O
O
R
O
R
R
Formation
Formation
R
O
O
R
R
OH
OH
Reactions
Reactions
NH22
NH
R NH
NH22
R
O
R
R C
C N
N
R
OR'
OR'
11H
13
NMR, 13
C NMR,
NMR, IR,
IR, MS
MS
H NMR,
C
The Formation of Amides
H++
R C N + H22O
OH
R C NH
O
R C NH22
Nitrile
CH33
O
C Cl + 2 NH33
CH33
O
C NH22
CH33
O
C NH22
+
CH33
CH33
O
C NH22
+
HO CH2CH33
+
NH44+ Cl--
Acid Chloride
CH33
O
C O
O
C CH33 + 2 NH33
O
+
C O-- NH4
Anhydride
CH33
O
C O
CH22CH33 +
Ester
NH33
Mechanisms
CH
CH33
O
O
NH33
C
C Cl
Cl ++ 22 NH
CH
CH33
O
O
C
C NH
NH22 ++
NH
NH44++ Cl
Cl--
NH
NH33
CH
CH33
O
O
C
C Cl
Cl
H
H
CH
CH33
NH
NH33
O
O
C
C Cl
Cl
NH
NH22
CH
CH33
NH3
H
CH3
C
NH3
H
O
Cl
NH22
H
O
H
O
C
NH33++ Cl
Cl-C NH
NH22 ++ NH
CH3
O
C
Cl
NH 2
Halides are great leaving groups
Mechanisms
H++
R C N + H22O
OH
R C NH
O
R C NH2
H++
R C N
H2O
H+
R C N H
O
H
H
R C N H
O
H
H++
R C N H
O
H
H
H
R C N H
H
O
H
Regenerated acid catalyst
H
R C N H
O
13C NMR and IR
13C NMR spectra
Carbonyl carbon: 180 ppm
Alkyl carbon: 20 ppm
of Amide
IR spectra
Carbonyl group: 1700 cm-1
N-H group: 3200 cm-1
- Physicians obtain laboratory values and perform diagnostic tests
- Organic chemists obtain spectroscopic data and perform model reactions
The Chemistry of Amides
What compounds can we make
from the amide functional group?
The Chemistry of Amides
CH33
O
C NH22
HCl
+
CH3
H22O
O
C OH
+
NH4++ Cl-
Carboxylic acid
CH33
O
C NH22
CH33
O
C NH22 +
1. LiAlH4, Et22O
2. H22O
Br2
CH33 CH22 NH22
Amine
+
2NaOH
CH33 NH22 +
Amine
CO2
Stability of Amides
O
O
R
R
O
O
N
N
H
H
H
H
O
O
H
H
H
H
R
R
O
O
R
R
R
R
NH
NH
NH22
NH
H
H
NH2
NH
Less electrophilic that other carbonyl functional group
Amides and Amino Acids
O
H2N CHC OH
R
O
H22N CHC OH
CH33
Alanine
O
H2N
O
H22N CHC OH
CH22
CH22
CH22
NH
C NH
NH22
Arginine
OH
R
O
H22N CHC OH
CH22
CH22
CH22
CH22
NH22
Lysine
Amides and Amino Acids
Penicillin Binding Protein
O
O
O
O
O
O
N CH C NH CHC NHCH C OH
OH
H22N
CH33
CH22
CH22
CH22
CH22
CH22
CH22
NH
NH
CH22
NH NH
NH22
C NH
NH
NH22
G-coupled Protein Receptor
Na/K Channel