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. 2009 Aug 20;11(16):3590-3.
doi: 10.1021/ol901311m.

Oligomerization route to Py-Im polyamide macrocycles

David M Chenoweth  1 , Daniel A Harki, Peter B Dervan
Affiliations

Oligomerization route to Py-Im polyamide macrocycles

David M Chenoweth et al. Org Lett. .

Abstract

Cyclic eight-ring pyrrole-imidazole polyamides are sequence-specific DNA-binding small molecules that are cell permeable and can regulate endogenous gene expression. Syntheses of cyclic polyamides have been achieved by solid-phase and solution-phase methods. A rapid solution-phase oligomerization approach to eight-ring symmetrical cyclic polyamides yields 12- and 16-membered macrocycles as well. A preference for DNA binding by the 8- and 16-membered oligomers was observed over the 12-ring macrocycle, which we attributed to a conformational constraint not present in the smaller and larger systems.

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Figures

Figure 1
Figure 1
Structures of macrocyclic polyamides 1z–3z and 1–3, and their ball-and-stick models. Polyamide shorthand code: closed circles, Im monomer; open circles, Py monomer.
Figure 2
Figure 2
Reverse phase HPLC analysis (20 hr) of the oligomerization reaction revealing products 1z, 2z, and 3z. Peaks were identified by high-resolution mass spectrometry following isolation and Cbz-deprotection.
Scheme 1
Scheme 1
Synthesis of macrocyclic polyamides 1–3 and higher order cycles by oligomerization of bifunctional intermediate 5.
See this image and copyright information in PMC

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