期刊
TETRAHEDRON
卷 69, 期 36, 页码 7683-7691出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tet.2013.05.060
关键词
Peptidomimetic; Macrocycle; Friedel-Crafts; Diversity; NMR solution structure
资金
- National Cancer Institute [PO1 CA95471]
- Donald J. & Jane M. Cram Endowment
- NSF [DGE-0707424]
- National Science Foundation [CHE-1048804]
- Direct For Mathematical & Physical Scien [1048804] Funding Source: National Science Foundation
- Division Of Chemistry [1048804] Funding Source: National Science Foundation
Macrocyclic peptidomimetics are valuable in research and serve as lead compounds in drug discovery efforts. New methods to prepare such structures are of considerable interest. In this pilot study, we show that an organic template harboring a latent cinnamyl cation participates in novel Friedel Crafts macrocyclization reactions with tryptophan. Upon joining the template to Trp-Trp-Tyr, a single operation efficiently generates eight unique macrocycles. Each has been isolated and thoroughly characterized. Product distribution as a function of Bronsted and/or Lewis acidic conditions was explored, and outcomes were compared to rearrangements induced within a corresponding tyrosine-linked cyclic ether. The solution structure of a new macrocyclic pyrroloindoline was solved using a combination of two-dimensional NMR methods and molecular mechanics simulations. Template-induced structural diversification of peptide sequences harboring aromatic residues has potential to create myriad macrocycles that target surfaces involved in protein protein interactions. (C) 2013 Elsevier Ltd. All rights reserved.
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