Transcript Starting Materials for the Synthesis Of Parasite

Synthesis of Chalcones:
Starting Materials for
the Synthesis Of
Parasite-targeted
Compounds
Sarah Canché
Lee Lab Group
Malaria, Leishmaniasis, and
Trypanosomiasis
 Diseases
caused by
protozoan
parasites
transmitted by
mosquitoes,
sand flies, and
tsetse flies
Some Symptoms
Malaria:
 Dry cough, fever, headache,
fatigue, body aches
Leishmaniasis:
 Skin sores, fever, visceral swelling
Trypanosomiasis:
 Muscle and joint aches, fever,
confusion, slurred speech
Widespread Problem:
Malaria:
 1-3 million deaths per year
Trypanosomiasis:
 50,000 to 70,000 cases per year
Leishmaniasis:
 10-15 million have it, with 1.5 to 2
million new cases per year
 Treatment for these diseases is
expensive and not always
effective
 Parasites can develop resistance
 Need to make treatments that are
more affordable and effective
Pentamidine and Furamidine
 Molecule currently being
used to fight parasitic
diseases
O
O
H2N
NH2
+
+
NH2
NH2
Pentamidine
 Destroys parasite DNA
H2N
 Molecule that has been
proven to help fight
parasitic diseases.
 Goal: Make a molecule
similar to this
 Increase potency
 Cheaper to produce
+
NH2
NH2
+
NH2
NH2
Furamidine
S
N NH
HN
+
NH2
H2N
O
+
NH2
+
H2N
NH
+
NH2
NH2
NH2
Synthetic Pathways
Diarylpyrazolediamidine Synthesis
O
O
O
CH3
H
15 M NaOH
R'
K2CO3
35% H2O2
CH3OH
95% Ethanol
R
R
R'
O
O
R'
R
N NH
H2N
NH2
+
+
NH2
H2N
Hydrazine Hydrate
p-Toluenesulfonic Acid
Xylenes
Reflux
N NH
1. Acetyl Chloride
dry MeOH
R'
R
2. NH3
dry MeOH, 0*C
R, R'=CN
Thioxopyrimidine Synthesis
S
O
R
Thiourea
K2CO3
R'
EtOH
Reflux
HN
R
NH
R'
How to synthesize chalcones:
Method 1
O
O
O
CH3
H
15 M NaOH
R'
95% Ethanol
R
R
R'
To make…
O
NC
OCH 3
86% yield
O
94% yield
H3CO
CN
Method 2
O
CH3
R
O
O
1 M NaOH
+
H
R
MeOH
Reflux
NC
6 M NaOH
MeOH
Reflux
CN
65% yield
O
94% yield
H3CO
OCH 3
•Methanol added to flask
•Reaction mixture heated to reflux
•1 M NaOH added to the mixture
•Solid forms
•Solid collected by vacuum filtration
What I learned





Run an NMR
Run an IR
Perform TLC analysis
ChemDraw
Rotovap
Acknowledgements
 Dr. Moses Lee
 Drs. Toni Brown & Hilary Mackay
 Kristin Dittenhafer
 Lee Lab Group
 REACH
 Hope College Chemistry
Department
 Conjura Pharmaceuticals, LLC