John R. Williams

 

John Williams

Professor

B.S. (1962), University of Western Australia, Perth, W.A., 1st Class (Hons)
Ph.D. (1966) University of Western Australia, Perth, W.A.
NIH Postdoctoral Fellow ('66-67) NIH, Bethesda, MD, ('67-'68) Columbia University

OFFICE
Beury Hall 440


MAILING ADDRESS

Department of Chemistry
Beury Hall 130
1901 N. 13th Street
Philadelphia, PA 19122


PHONE

office: 215-204-7144
fax: 215-204-1532
lab: 215-204-6209


E-MAIL
john.r.williams@temple.edu

 

RESEARCH GROUP

Medicinal / Organic

Research Interests

Design, Synthesis and Testing of Biologically Active Compounds

Our aim is to develop new methods for organic synthesis and to apply these methods in the preparation of biologically active steroids and natural products. Pavoninin-4 (1), is one of six steroidal N-acetylglucosamides that protect fish from attack by sharks. This novel steroid has interesting hydrophobic and hydrophilic regions that result in structures with potent ichthyotoxic, hemolytic and shark-repelling properties. A synthesis of 1 and close analogs is currently in progress. This synthesis has resulted in the development of a modified Clemmensen reaction and an increased understanding of the Leuche reaction. New, novel steroid structures are being designed, synthesized and will be tested by Dr. Gruber at the Bimini Biological Field Station in the Bahamas.

Squalamine 2, is a novel aminosteroid that protects sharks from infection. This steroid has potent antibiotic activity against both gram positive and gram negative bacteria. Since some bacteria have developed resistance to all the currently available antibiotics, there is a great need for new antibiotics. This novel structure is an excellent lead compound for the development of new drugs, since it is a natural antibiotic produced by evolution. Furthermore 2 has antiangiogenic properties resulting in anti-cancer properties and testing for the treatment of macular degeneration. New structures based on 2 are being synthesized and tested by Dr. Tuszinski of the Temple Biology Department.


Selected Publications

Williams, J.R.; Chai, D. and Wright, D. “Synthesis of (25R)-26-Hydroxycholesterol”, Steroids, (2002), 67, 1041-1044.


Williams, J.R.; Chai, D.; Gong, H.; Zhao, W. and Wright D. “Studies toward the Synthesis of the Shark Repellent Pavoninin-5, Lipids, (2002), 37, 1193-1195.


Williams, J. R.; Chai, D.; Bloxton II, J. D.; Gong H. and Solvibile W. “Synthesis of the Aglycone of 26-O-Deacetyl Pavoninin-5, Tetrahedron (2003), 59, 3183-3188.


Williams, J. R.; Gong, H.; Hoff, N and Olubodun, O. “a-Hydroxylation at C-15 and C-16 in Cholesterol: Synthesis of (25R)-5a-Cholesta-3b,15a,26-triol and (25R)-5a-Cholesta-3b,16a,26-triol from Diosgenin”. Organic Letters (2004), 6, 269-271.

Williams, J. R.; Ma, J.; Wepplo, P. and Paclin R. A. “Synthesis and Intramolecular Reactions of trans-Cyclohexyl-1,2-bisacrylate J. Org. Chem. (2004), March


Williams, J. R.; Ma, J.; Wepplo, P. and Paclin R. A. "Synthesis and Intramolecular Reactions of trans -Cyclohexyl-1,2-bisacrylate" J. Org. Chem . (2004) , 69 , 1730-1733.


Williams, J. R. and Gong H. "Isolation and Synthesis of Shark-Repelling Saponins" Lipids (2004) , 39, 795-799.


Williams JR.; Gong H.; Hoff N. “Synthesis of the shark repellent pavoninin-4” Journal of Organic Chemistry 70 (26): 10732-10736 (2005).


Gong H.; Williams JR. "Synthesis of the aglycone of the shark repellent pavoninin-4 using remote funtionalization" Organic Letters (2006) , 8 (11), 2253-2255.


Williams JR.; Gong H. "Biological activities and syntheses of steroidal saponins: the shark-repelling pavoninins" Lipids (2007) , 42 (1), 77-86.

"Shark Dive"


Diving with reef sharks at the Bimini Biological Field Station.

JRW is fourth from the left.

"Preparing to Administer a New Repellent"

The shark is lying motionless in a state of "tonic immobility" The repellent is added to the water in front of the shark's mouth and its reaction to the compound measured.