Efficient kinetic macrocyclization

Wen Feng, Kazuhiro Yamato, Liuqing Yang, Joseph S. Ferguson, Lijian Zhong, Shuliang Zou, Lihua Yuan, Xiao Cheng Zeng, Bing Gong

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107 Scopus citations

Abstract

In this article, the highly efficient formation of a series of recently discovered aromatic oligoamide macrocycles consisting of six meta-linked residues is first discussed. The macrocycles, with their backbones rigidified by three-center hydrogen bonds, were found to form in high yields that deviate dramatically from the theoretically allowed value obtained from kinetic simulation of a typical kinetically controlled macrocy-clization reaction. The folding of the uncyclized six-residue oligomeric precursors, which belong to a class of backbone-rigidified oligoamides that have been demonstrated by us to adopt well-defined crescent conformations, plays a critical role in the observed high efficiency. Out of two possible mechanisms, one is consistent with experimental results obtained from the coupling of crescent oligoamides of different lengths, which suggests a remote steric effect that discourages the formation of oligomers having lengths longer than the backbone of the six-residue precursors. The suggested mechanism is supported by the efficient formation of very large aromatic oligoamide macrocycles consisting of alternating meta-and para-linked residues. These large macrocycles, having H-bond-rigidified backbones and large internal lumens, are formed in high (>80%) yields on the basis of one-step, multicomponent macrocyclization reactions. The condensation of monomeric meta-diamines and a para-diacid chloride leads to the efficient formation of macrocycles with 14, 16, and 18 residues, corresponding to 70-, 80-, and 90-membered rings that contain internal cavities of 2.2, 2.5, and 2.9 nm across. In addition, the condensation between trimeric or pentameric diamines and a monomeric diacid chloride had resulted in the selective formation of single macrocyclic products with 16 or 18 residues. The efficient formation of the macrocycles, along with the absence of other noncyclic oligomeric and polymeric byproducts, is in sharp contrast to the poor yields associated with most kinetically controlled macrocyclization reactions. This system represents a rare example of highly efficient kinetic macrocyclization reactions involving large numbers of reacting units, which provides very large, shape-persistent macrocycles.

Original languageEnglish (US)
Pages (from-to)2629-2637
Number of pages9
JournalJournal of the American Chemical Society
Volume131
Issue number7
DOIs
Publication statusPublished - Feb 25 2009

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Feng, W., Yamato, K., Yang, L., Ferguson, J. S., Zhong, L., Zou, S., ... Gong, B. (2009). Efficient kinetic macrocyclization. Journal of the American Chemical Society, 131(7), 2629-2637. https://doi.org/10.1021/ja807935y