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Synthesis 2004(11): 1759-1766  
DOI: 10.1055/s-2004-829120
PAPER
© Georg Thieme Verlag Stuttgart · New York

Direct Reductive Alkylation of Amino Acids: Synthesis of Bifunctional Chelates for Nuclear Imaging

Murali K. Levadalaa, Sangeeta Ray Banerjeea, Kevin P. Marescab, John W. Babichb, Jon Zubieta*a
a Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA
Fax: +1(315)4434070; e-Mail: jazubiet@syr.edu;
b Molecular Insight Pharmaceuticals, Inc., 160 Second St., Cambridge, MA 02142, USA
Further Information

Publication History

Received 30 February 2004
Publication Date:
01 July 2004 (online)

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Abstract

A family of effective bifunctional chelators for technetium- and rhenium-based radiopharmaceuticals was conveniently synthesized in high yields through direct reductive N-alkylations of amino acids and their analogues with aldehydes, using NaBH(OAc)3 as an efficient reagent. The mono-, di-, tetra- and even mixed alkylated amino acid derivatives were all prepared in one-pot synthesis.

Key words

reductive alkylation - amino acids - bifunctional chelators - radiopharmaceuticals - sodium triacetoxyborohydride

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24

Table [1] , Entry 6 (C22 H25 N3 O3, formula weight 379.45): Orthorhombic, space group P212121 with a = 7.3392(4) Å, b = 15.0539(7) Å, c = 17.9286(9) Å, V = 1980.82(17) Å3, Z = 4, R1 = 0.0556, wR2 = 0.1079 (F2, all data). Full details on the crystal structure of 6 are available from the authors.

25

The imine to aldehyde ratio was in the range of 1: 0.10-0.20, as determined by 1H NMR spectrum.

28

Maresca, K. P.; Levadala, M. K.; Banerjee, S. R.; Babich, J. W.; Zubieta, J., unpublished results.