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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