Synthesis of sulfur-bridged bis-phenanthroline molecules for telomerase inhibition

CHED 499

Amber D. Leenstra, amber.leenstra@uvm.edu and A. Paul Krapcho, pkrapcho@zoo.uvm.edu. Department of Chemistry, University of Vermont, Cook Physical Science Building, Burlington, VT 05405
Several telomerase-inhibiting molecules have recently been synthesized as potent anticancer drugs, based on their ability to stabilize telomeric DNA via the G-quadruplex structure. We detail the synthesis and characterization of a set of molecules similar to the porphyrinoid class of compounds which have been shown to be potent telomerase-inhibiting drugs. Our target molecule, a sulfur-bridged macrocycle, was successfully obtained by the joining of 2,9-dichloro-1,10-phenanthroline and 1,10-dihydro-1,10-phenanthroline-2,9-dithione. The syntheses of the two phenanthroline units are described, as well as the single-step cyclization of the moieties to form the macrocycle adduct. A related molecule, 5-cyano-2,9-dichloro-1,10-phenanthroline, has been synthesized as well. Efforts to form the macrocycle using the cyano analog will be explored. The cyano side chain may be modified into a carboxylic acid, followed by conversion to an amide, which is thought to provide additional support in the stabilization of the G-quadruplex.

 

Undergraduate Research Poster Session: Organic Chemistry
11:00 AM-1:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster

Division of Chemical Education

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008