Synthesis 2011(1): 57-64  
DOI: 10.1055/s-0030-1258337
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

New Synthetic Approach for the Incorporation of 3-Hydroxypyridin-2(1H)-one (3,2-HOPO) Ligands: Synthesis of Structurally Diverse Poly 3,2-HOPO Chelators

Jayanthi Arumugam, Hayley A. Brown, Hollie K. Jacobs*, Aravamudan S. Gopalan*
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003-8001, USA
Fax: +1(575)6462649; e-Mail: hjacobs@nmsu.edu; e-Mail: agopalan@nmsu.edu;
Further Information

Publication History

Received 22 September 2010
Publication Date:
26 November 2010 (online)

Abstract

The 3,2-HOPO sulfonamide reagent 3 was prepared from commercial 2,3-dihydroxypyridine in four steps in good yields. Sulfonamide 3 readily underwent selective alkylation with dibromides in the presence of base or could be coupled to alcohols using Mitsunobu conditions. The utility of this nucleophilic 3-hydroxypyridin-2(1H)-one (3,2-HOPO) reagent was demonstrated by the synthesis of some tris- and tetrakis-3,2-HOPO chelators. This approach for tethering 3,2-HOPO ligands is unique and flexible as shown by the preparation of 3,2-HOPO/iminocarboxylic acid chelator 17.

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11

The preparation of 3,2-HOPO amine 2 by a longer synthetic sequence has been reported. See reference 8a.

13

Attempts to prepare either bis-3,2-HOPO 6 or tris-3,2-HOPO 7 using reductive amination of 3,2-HOPO amine 2 with the aldehyde of 3,2-HOPO alcohol 4 (prepared by Swern oxidation of 4) led to mixtures of products.