Samuel E. Watson Professor Organic Chemistry

Office: M701
Phone: (718)488-1027
Fax:     (718)488-1465
Email: swatson@liu.edu

Education:

Ph.D. Princeton, 1995, synthetic organic chemistry
M.S. San Francisco State University, 1986, synthetic organic chemistry
B.A. Stanford University, 1971.

Teaching Interests: beginning organic chemistry, advanced organic chemistry, bio-organic chemistry, heterocyclic chemistry, organic synthesis, organic reaction mechanisms.

Research Interests: Design and Synthesis of biologically active small organic molecules for use as potential new drugs. Development of new and very efficient ways of making complicated organic molecules.

Research Projects Currently in Progress: As a synthetic organic chemist I am interested in the design and synthesis of relatively small molecule inhibitors of biologically and medicinally significant enzymes. Current work is focused in two general areas, both involving the development of novel anti-tumor therapeutics of potential interest in cancer chemotherapy.

Project I One project involves the design and synthesis of peptidomimetic inhibitors of farnesyl transferase. This enzyme is involved in attaching a farnesyl group to one of the Ras proteins, a key messenger in the signalling pathway that controls the onset of the malignant growth signal in tumor cells. Recent studies have shown that inhibition of this enzyme through mimicry of the last four residues of the natural Ras protein can prevent the turning-on of the signal for cell division. Under the assumption that the terminal four residues adopt a Type I beta-turn conformation in their enzme-bound state, a series of compounds containing proteolytically insensitive bicyclic skeletons that lock the critical recognition elements in place have been designed using computer-aided molecular modeling techniques. Inhibition of farnesyl transferase by these peptidomimetics represents an exciting new approach to cancer chemotherapy and syntheses of these compounds are being developed.

Project II Another area of interest is in the synthesis of several organic molecules, the makaluvamines and Wakayin, that were recently discovered in organisms living in the deep ocean off the coast of Fiji. Many marine organisms have developed natural defense systems to protect them against predators and in some cases these molecules can be useful agents in the fight against human diseases. The makaluvamines and Wakayin were found to have extremely potent selective toxicity toward tumor cells and two of the compounds were found to be very powerful inhibitors of one of the enzymes involved in the unwinding of DNA that is necessary for replication and transcription to occur. Since rapidly dividing cancer cells have a huge demand for DNA, inhibition of this enzyme may be a useful new chemotherapeutic approach. These molecules occur naturally in only minute quantities and larger supplies are necessary for further biological studies. Work aimed at the syntheses of these complicated molecules is therefore underway.

Students working in my laboratory become familiar with a wide variety of synthetic techniques. We also learn how to purify and charaterize organic compounds and so become familiar with the use of many of the instruments in the department including the nuclear magnetic resoance instrument, the infrared spectrometer, the gas chromatograph and the mass spectrometer.

Grants

1. Co-Principal Investigator, along with Dr. Andreas Zavitsas, Principal Investigator, and Dr. Dennis Curley, Co-Principal Investigator, on the Rennovation Grant awarded to the Science Division at LIU by the National Science Foundation for the rennovation of existing science facilities in the chemistry and biology departments. $1.7 million has been awarded by the National Science Foundation and ~$500,00 has been recieved as matching funds from Long Island University.

2. Principal Invesitgator, Individual Research Grant from the National Institutes of Health for support of my studies in "The Design and Synthesis of Novel Peptidomimetics as Farnesyl Transferase Inhibitors and new Anti-tumor Agents". This grant consists of $214,000 to be disbursed over two years for the purchase of research equipment and supplies and for the support of two graduate students. The grant was awarded under the Minority Biomedical Research Support (MBRS) program, with Dr. R. Oki, acting as the project director of the overall program. This work involves an active collaboration with Dr. Patrick Casey of the Duke University Medical School.

3. Co-Principal Investigator, with Dr. Fernando Commodari, in the $320,000 Bridge Program Grant recently awarded to the Science Division of the Brooklyn Campus by the National Institutes of Health. The purpose of this grant is to foster collaboration between our campus and the Albert Einstein College of Medicine. Selected minority students will be given full scholarships at LIU-Brooklyn covering both tuition and a stipend inorder to pursue reseach that will lead concurrently to completion of an M.S. degree at LIU-Brooklyn and entry into a Ph.D. program at Albert Einstein College of Mediicine. My sub-proposal, written in collaboration with Dr. Vern Schramm, Chair, Department of Biochemistry, Albert Einstein College of Medicine, was recommended for funding. One graduate student is to be supported by this grant.

Publications

1. Novel Methodology for the Preparation of 5-Substituted Tetrahydro[2,3-D]Pyrimidines, Watson, S. E., accepted for publication by Synthetic Communications to appear in Volume 28, Number 10.

2. Succinct Synthesis of 2-Substituted Pyrroles, Watson, S. E.; Markovich, Anatoly, accepted for publication by Synthetic Communications to appear in Volume 28, Number 20.

3. Synthesis of Protected 5-Formyl Pyrido[2,3-d]pyrimidine via a 2,3,4-Trisubstituted Pyridine using an Ortho-lithiation Strategy, submitted to Heterocycles 6/3/98.

4. Silicon-Containing Antifolates, Taylor, E. C.; Watson, S. E.; Chaudhari, R.; submitted to Tetrahedron

5. The Design and Synthesis of Novel Folates as Potential Anti-tumor Agents, Watson, S. E., Ph.D. Thesis, Princeton University, 1995.

6. Dichloroketene Additions to Small Ring Systems; Synthetic Applications, Watson, S. E.; M. S. Thesis, San Francsico State University, 1986.