Acknowledgements Special thanks to Dr. Vincent Gullo, Dr. Arnold Demain,

Maria Falzone, DSSI, and R.I.S.E.

Conclusions and Future Work

•  Steps 1 and 2 completed successfully. •  Step 3 to final product.

•  Biological assay indicates the final reaction is working, but not working well based on TLC.

•  In order to improve the reaction: •  Heat the reaction for a longer period

of time or at a higher temperature. •  Use different reagent other than

tirphenylphosphine iodine. •  Continue these reactions and test for biological activity.

Step 1 Results Analytical TLC Preparative TLC

Fig.2. Analytical TLC and Preparative TLC showing where compound 1 is found on the plates (circled

bands).

Fig.3. H1NMR and LCMS confirm that the reaction was completed successfully. All peaks match the chemical

structure of the product in the H1NMR and the molecular weight matches that of the product in the

LCMS.

Step 2 and 3 Results Compound 2 was confirmed by LCMS, H1NMR, and by

analytical and preparative TLC.

Fig.4. Compound 3 was put onto a Staphylococcus aureus agar plate and left to incubate for the night. The

spot labeled “R3j” appeared to have a zone of inhibition, meaning that compound 3 seemed to have

antimicrobial properties.

N

O

H

Cl

CH3

N

O

R

Cl

CH3

N

HN

R

Cl

OH

N

N

R

Cl

Step 2 Step 1

Step 3

WH 472-21

Reagents: (Step 1) NaH, Dimethylformamide (DMF), Bromomethyl methyl ether; (Step 2) 3-aminopropanol, water/ice;

(Step 3) Triphenyl phosphine, imidazole, DMF, Iodine

1

2 3

Fig 1. Mazindol Analogues As Potential Inhibitors of the Cocaine Binding Site At The Dopamine Transporter. Journal of

Medicinal Chemistry 45 (19): 4097-4109.

R=OCH3

Reaction Scheme

Experimental Methods Methods

Step 1 N2 gas, 0oC, 2 hours

Step 2 Reflux, 180oC, 3 hours

Step 3 Dry, 50oC – 1 hour, 25oC - Overnight

Identification of the product was done using analytical thin layer chromatography (TLC). Afterwards, the product of each step

was purified using preparative TLC. The purified product’s chemical structure was determined by using proton nuclear

magnetic resonance (H1NMR) and liquid chromatography mass spectroscopy (LCMS).

WH 144-16 WH 76-24

N

N

Cl

H3C

Dr. William J. Houlihan, a former RISE fellow, synthesized about 400 compounds at Drew University. These compounds were tested for antibacterial activity. The two

that had the most activity were discovered by Christopher Damurjian and Christian Maggio; the two compounds were WH 144-16 and WH 76-24. Kimy Yeung had

previously studied the structural relationships between these two compounds and she discovered that they both have a para chlorine on an aromatic ring and contain

an isoindole.

Previous Studies

N

HO

Cl

N

Development of a Synthetic Route to New Antibacterials Justin Pezick, Drew University, Madison NJ

What are antibacterials? •  Compounds that are natural and synthetic. •  Selectively kill or inhibit growth of bacteria without injuring the host. Is there a need for new antibacterials? •  Bacteria are becoming resistant to current antibacterials •  There has been a large decline in antibacterial discovery due to mergers and

switching resources to other diseases. •  Emergence of new infectious diseases. What is a synthetic route? •  The route by which a given compound is synthesized. •  Development of new synthetic routes can lead to the creation of new

antibacterials.

The goal of this research product was to develop an effective route to synthesizing 6-(-4-cholrophenyl)-6-methoxymethyl-2,3,4,6-tetrahydropyrimido-[2,1-a]-isoindole

and test it for antimicrobial activity.

Introduction

Goal

N

O

H

Cl

CH3

N

N

Cl

O

WH 472-21