Alternative synthesis of the anti-baldness compound RU58841

Leonard, Matthew J.; Lingham, Anthony R.; Niere, Julie O.; Jackson, Neale; McKay, Peter G.; Hügel, Helmut

doi:10.1039/c4ra00332b

Cited by 6 publications

(10 citation statements)

References 11 publications

(17 reference statements)

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“…In Tables , we listed all published α‐amino acid derivatives and (either linear or, more rarely, cyclic) peptides to the decamer level where single or consecutive fully‐extended (C 5 ) structures were identified by X‐ray diffraction in the last 5/6 years. A few, still unpublished 3D‐structures, characterized by the C 5 form and solved in the Padova laboratory, are presented in Table…”

Section: Detailed Literature Survey On Peptides Since 2012mentioning

confidence: 99%

The fully‐extended conformation in peptides and proteins

et al. 2018

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The intramolecularly H‐bonded, fully‐extended conformation (C5) of an α‐amino acid residue (and the resulting 2.05‐helix obtained via its propagation) is one of the least extensively investigated types of peptide and protein backbone secondary structure. This situation does still currently occur despite its unique ability to enjoy by far the largest separation per residue among peptide conformations. In this article, we offer a detailed update of our present knowledge on this intriguing 3D‐structure of peptides in the crystal state as obtained from recently published investigations, complemented by a statistical analysis for its occurrence in the crystal structures of α‐amino acid derivatives and peptides available in the Cambridge Structural Database. We have expanded this useful information to the results of a bioinformatics analysis performed on this (so far largely unappreciated) conformation authenticated in all proteins solved by X‐ray diffraction to a resolution of ≤ 1.5 Å. In the last section, we describe the results of our DFT calculations on the conformational preferences of a set of homopeptides (from monomer to octamer) based on as many as six proteins and two noncoded, carefully selected, α‐amino acids. From this literature survey integrated by new energy calculations, we have definitely provided strong support to the thesis that this polypeptide 3D‐structure does indeed exist, it should be not neglected in future studies by structural biochemists, and it represents a very attractive, novel backbone for applications for organic, medicinal, and biomaterials chemists.

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Section: Detailed Literature Survey On Peptides Since 2012mentioning

confidence: 99%

The fully‐extended conformation in peptides and proteins

et al. 2018

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“…This compound has been previously reported. 21 1-Methyl-3-phenylhydantoin 9g. Yield: 54% (207 mg, 1.09 mmol).…”

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confidence: 99%

Copper-Mediated N-Arylations of Hydantoins

Thilmany

Gérard

Vanoost³

et al. 2018

J. Org. Chem.

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A set of two broadly applicable procedures for the N-arylation of hydantoins is reported. The first one relies on the use of stoichiometric copper(I) oxide under ligandand base-free conditions and enables a clean regioselective arylation at the N 3 nitrogen atom, while the second one is based on the use of catalytic copper(I) iodide and trans-N,N′-dimethylcyclohexane-1,2-diamine and promotes arylation at the N 1 nitrogen atom. Importantly, the combination of these two procedures affords a straightforward entry to diarylated hydantoins.

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“…However, we have found that the Kornblum substitution does proceed on a tertiary centre that is alpha to an anilide carbonyl group. We have hence used the Kornblum substitution to prepare an α-nitroisobutyranilide (2) in order to perform an alternative synthesis of the hydantoin anti-baldness compound RU58841, a process that we published in 2014 [10]. The reaction was simple and performed in high yield with low cost materials (Figure 3).…”

Section: Figure 2 the Kornblum Substitutionmentioning

confidence: 99%

“…(1). Characterization data for 1 are provided in our 2014 publication [10] where it is given the correct IUPAC name of "2-Bromo-N- [4-cyano-3-(trifluoromethyl)phenyl]-2-methylpro panamide".…”

Section: Acylation Reactionsmentioning

confidence: 99%