Scheme 1. Standard automated DNA solid-phase synthesis.

Base Labeling

B ase-labeled nucleosides are typically prepared by reacting a halide- or alkyny 1-modified base with a desired redox probe, using a palladium-catalyzed cross-coupling reaction.12-14'41'53 Probes such as metal complexes possess a number of favorable properties including tunable electronic structures, reversible electrochemical behavior, and emissive spectroscopic states. As shown in Scheme 2, a Pd(PPh3)4 cross-coupling reaction between the ruthenium complex, 3, and 2'-deoxy-3',5'-dibenzoyloxy-5-iodouridine, 5, affords the metallo-nucleoside, 6.13,62 Benzoyl deprotection in methanolic ammonia, followed by reaction with 4,4'-dimethoxytrityl chloride and 2-cyanoethyl-JY,yV'-diisopropylchlorophos-phoramidite, yields the ruthenium-nucleoside phosphoramidite, 9, ready for automated solid-phase synthesis as shown in Scheme 1.

Compound 2: 4'-Methyl-2,2'-bipyridine-4-propargylamide. 4'-Methyl-2,2'-bipyridine-4-carboxylic acid63 (1 mmol; 1), propargylamine hydrochloride

62 S. I. Khan, A. E. Beilstein, G. D. Smith, M. Sykora, and M. W. Grinstaff, Inorg. Chem. 38, 2411 (1999).

63 D. G. McCafferty, B. M. Bishop, C. G. Wall, S. G. Hughes, S. L. Mecklenberg, T. J. Meyer, and B. w. Erickson, Tetrahedron 51, 1093 (1995).

0 0

Post a comment