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Carmen Cannon
Vickie Geisler
GEMS Summer Research ‘07
26 July 2007
Synthesis of Garner’s Aldehyde
Introduction
Dr. Philip Garner, a chemist from the University of Pittsburg, developed the first
synthesis of 1,1-dimethylethyl 4-formyl-2, 2-dimethyl-oxazolidine-3-carboxylate, known to
many as Garner’s aldehyde. Garner’s aldehyde is the first step to form analogs of sphingosine to
inhibit the enzyme Protein Kinase C (PKC) that promotes cell growth and cell differentiation.
The formation of the analogs is believed to hinder tumor cells from spreading, which can be a
useful tool in the steadfast discovery for a cure for cancer. The purpose of this research is to form
Garner’s aldehyde in our lab using the outline literature from Organic Syntheses. The aldehyde
that is made can be used for the next step in the production of sphingosine analogs.
Method
The first step involved the protection of the acidic amine hydrogens on L-serine methyl
ester using a Boc group. Step two protected the remaining acidic hydrogen via the creation of an
oxazolidine ring using dimethoxypropane. Reduction of the ester to the aldehyde is to be
accomplished in the last two steps.
O
NH3 Cl-
H3CO
HN
HO
O
OCH3
2
O
Boc2O, Et3N
HO
THF
O
BF3-OEt2
CH3
O
L- serine methyl ester
O
OH
O
O
CH3
O
O
N
H
LAH
Boc
THF
O
N
DMSO
Boc
i-Pr2NEt
O
N
Boc
"Garner's Aldehyde"
We decided to focus on the first two steps of our experiment because we were not
producing enough pure product to continue to Rxn C. The literature called for 10.4-10.8 g of
oxazolidine methyl ester1 and we were producing between 1.3-3.0 g. We changed the method by
using distilled acetone and dimethoxypropane in order to gain more pure results. We also
decreased the amount of diethyl ether during our extraction of the organic and aqueous layer in
Rxn A in order to reduce the amount of solvent that had to be evaporated from our final product.
The Experience
Working with the GEMS Summer Research allowed me to gain more experience in
working in lab environment. Before this summer my knowledge of the lab was limited to the
basic skills and techniques were we taught in introductory chemistry. Lab was not reinforcing to
help us retain the material we learned in class. Our labs were just mere activities to relieve the
demanding lecture schedule. AS one can predict, my first day in Dr. Geisler’s lab was a bit
overwhelming. There were many bottles of chemicals, many of which I never heard of or could
pronounce, various types of glassware and machines that I had never seen before in a lab. Also,
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the knowledge that my other lab partners in the lab had was a bit intimidating because I did not
understand many of the concepts that had learned in Organic chemistry.
Overall, I knew that I had to catch up on a lot and paid attention to what was going on so
I can pick up different techniques. One important concept that I learned while working in the lab
is precision is key. Being precise in measurements and technique can control the outcome in the
experiment. For example. my first trial of Reaction A and B had terrible yields and my results
did not mirror those that were in the literature. For Trial 2, I picked up different techniques from
my lab partners to increase the precision in my technique and my results were a lot better than
those in Trial 1. Another important concept was purification. Because our steps were so
sequnitial, making sure each product from one reaction to another was important. The most time
consuming but essential part to our reactions was the column chromatography. We ran many
columns so that we could get the most pure sample to continue on the next step. Without these
columns our results would have many impurities that would cause our yields to be irregular. Also
use of the H1 NMR machine allowed us to view what substances were in our products so that we
could continue on to our next step.
In our progression, we have been able to complete everything up to Rxn C but we have
combined our products together have enough to start Rxn D. We have discovered that our
products from Rxn B require more purification and results in a limited amount of product to
continue the process in Rxn C. As of now we have ran Rxn A & B numerous of times to try to
discover the problem that were are having in the transition from Rxn B to Rxn C. Trying
different solvents with our TLC analysis indicates that Rxn A may not be in completion when we
start Rxn B creating a problem in our products. Future research is to correct the problem in the
first two reactions and to ultimately make Garner’s Aldehyde for the sphingosine analogs.
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