Catalytic C-C coupling of N-substituted (pyridin-2-yl)-hydrazine derivatives for the synthesis of bioconjugates

ORGN 445

Cesear Corona1, Bj K. Bryant1, Trevor Luke1, and Jeffrey B. Arterburn2. (1) Department of Chemistry and Biochemistry MSC 3C, New Mexico State University, P.O. Box 30001, Las Cruces, NM 88003, (2) Department of Chemistry & Biochemistry MSC 3C, New Mexico State University, P.O. Box 30001, Las Cruces, NM 88003

There is currently a great deal of interest in the development of receptor-targeted Tc-99m radiopharmaceuticals for medical diagnostic imaging applications. 2-Hydrazinopyridine is an effective ligand for Tc/Re in oxidation states I-V. We have developed synthetic strategies for attaching this class of ligand to biomolecules using C-C coupling. We found that attempted Suzuki couplings of 1a with boronic acids were ineffective due to catalyst degradation; however, chelating phosphine ligands provided functional catalysts. Alternatively, N-alkyl substitution yielded hydrazine derivatives that coupled under diverse conditions, including ligand free and air stable carbopalladacycle catalysts. Furthermore, N-alkylation enables tuning of stereoelectronics, solubility, and further functionalization for chelation. Catalytic couplings of alkyne and alkene derivatives with 1 were also investigated. Herein, we discuss the synthesis of estradiol, biotin, and peptide conjugates of N-alkyl substituted (pyridin-2-yl)-hydrazines, and their complexation chemistry with Re(CO)3+.

Physical Organic, Materials, Heterocycles, Aromatics, Metal-Mediated Reactions 8:00 PM-10:00 PM, Tuesday, September 9, 2003 Hilton New York -- Americas Hall 1, Poster Division of Organic Chemistry The 226th ACS National Meeting, New York, NY, September 7-11, 2003