Vishal Sharma, Alexander Menke, Eric Simanek...Vishal Sharma, Alexander Menke, Eric Simanek...
Transcript of Vishal Sharma, Alexander Menke, Eric Simanek...Vishal Sharma, Alexander Menke, Eric Simanek...
PowerPoint Template ©2009 Texas Christian University, Center for Instructional Services. For Educational Use Only. Content is the property of the presenter and their resources.
AbstractIn chemistry, cyclic compounds of twelve or
more members including any hetero-atom are
considered macrocycles. Many bioactive natural
products containing macrocycles have been
isolated and synthesized. Some of the macrocyclic
antibiotics that have been found or synthesized are
vancomycin, daptomycin, polymyxin, bacitracin A
and azithromycin. Construction of macrocycles is
usually considered a challenging step in the
synthesis. Here, we represent synthesis of different
sized macrocycles by connecting two or more
cyanuric chloride molecules substituted with
various length amino acids to give rings of
different sizes. So far, we have been able to
synthesize macrocycles of 22, 24, 26, and 28
members by forming of dimers. Our goal to
influence that the length of carbon chains has on
ring formation as well as the solubility of these
molecules.
Results and Characterization
Future PlansThe future plan for this research is to expand
the library of homodimer macrocycles to include
different sizes and eventually heterodimers. The
interior of the ring could recognize guest molecules
or metal ions opening the possibility of using these
macrocycles to carry medicines. Solubility of these
macrocycles has been challenge so far. To enhance
the solubility, morpholine could be replaced with
hydrophilic groups such as 4-aminopiperdine. After
a sufficient amount of unique macrocycles are
acquired, the molecules will be put through a high
throughput screen to see if they can interfere with
protein-protein interactions, thus acting as drugs in
their own right.
Some of the planned macrocycles are shown
below.
BackgroundThe formation of macrocycles by ring-closure
is called macrocyclization. Ring closing reactions
do not favor the formation of large rings. Instead,
polymers tend to form. Macrocycles have been a
topic of research for decades due to their biological
activity, topology, and as tests of the limits of
synthetic methodology. Some classes of
macrocycles are relatively easy to synthesize, while
others present challenges. Antibiotics vancomycin,
fidaxomicin, nisin, azithromycin, and
clarithromycin contain different sized macrocycles.
Synthetic Schemes
Exploring Cyanuric Chloride Chemistry to Synthesize Macrocycles of Different Sizes
Vishal Sharma, Alexander Menke, Eric SimanekDepartment of Chemistry, Texas Christian University, Fort Worth, TX, 76129, USA
Acknowledgements• TCU SERC Grant
• TCU Department of Chemistry and Biochemistry
Clarithromycin Vancomycin
X = H R= methyl, ethyl
Table 1: List of macrocycles synthesized. (X = H)
Figure 1: 1H-NMR of macrocycle (M-2)
Figure 2: 1H-COSY of macrocycle
(M-2)
Figure 3: X-Ray crystal structure
of M-2
Figure 4: Mass spectrum of M-2.
Expected; m/z 612.31.
Observed; 613.37
vrs_V_51 #1 RT: 0.01 AV: 1 NL: 7.84E6
T: + c ESI Full ms [250.00-2000.00]
400 600 800 1000 1200 1400 1600 1800 2000
m/z
0
10
20
30
40
50
60
70
80
90
100
Relat
ive A
bund
ance
613.37
635.51
651.37
307.30 865.24
765.32326.24 903.37 1898.831476.741288.23 1622.26513.20 1147.09
Macrocycles n m Ring Size
1 1 1 22
2 1 2 24
3 1 3 26
4 2 1 24
5 2 2 26
6 2 3 28
X = CH3
R1 = isopropyl
R2 = 4-aminopiperdine
References:• Hamilton-Miller, J. M. Bacteriol. Rev. 1973, 37,
166-196