69955-04-0Relevant articles and documents
Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators
McCune, Christopher D.,Beio, Matthew L.,Sturdivant, Jill M.,De La Salud-Bea, Roberto,Darnell, Brendan M.,Berkowitz, David B.
, p. 14077 - 14089 (2017/10/17)
Developing specific chemical functionalities to deploy in biological environments for targeted enzyme inactivation lies at the heart of mechanism-based inhibitor development but also is central to other protein-tagging methods in modern chemical biology including activity-based protein profiling and proteolysis-targeting chimeras. We describe here a previously unknown class of potential PLP enzyme inactivators; namely, a family of quaternary, α-(1′-fluoro)vinyl amino acids, bearing the side chains of the cognate amino acids. These are obtained by the capture of suitably protected amino acid enolates with β,β-difluorovinyl phenyl sulfone, a new (1′-fluoro)vinyl cation equivalent, and an electrophile that previously eluded synthesis, capture and characterization. A significant variety of biologically relevant AA side chains are tolerated including those for alanine, valine, leucine, methionine, lysine, phenylalanine, tyrosine, and tryptophan. Following addition/elimination, the resulting transoid α-(1′-fluoro)-β-(phenylsulfonyl)vinyl AA-esters undergo smooth sulfone-stannane interchange to stereoselectively give the corresponding transoid α-(1′-fluoro)-β-(tributylstannyl)vinyl AA-esters. Protodestannylation and global deprotection then yield these sterically encumbered and densely functionalized quaternary amino acids. The α-(1′-fluoro)vinyl trigger, a potential allene-generating functionality originally proposed by Abeles, is now available in a quaternary AA context for the first time. In an initial test of this new inhibitor class, α-(1′-fluoro)vinyllysine is seen to act as a time-dependent, irreversible inactivator of lysine decarboxylase from Hafnia alvei. The enantiomers of the inhibitor could be resolved, and each is seen to give time-dependent inactivation with this enzyme. Kitz-Wilson analysis reveals similar inactivation parameters for the two antipodes, L-α-(1′-fluoro)vinyllysine (Ki = 630 ± 20 μM; t1/2 = 2.8 min) and D-α-(1′-fluoro)vinyllysine (Ki = 470 ± 30 μM; t1/2 = 3.6 min). The stage is now set for exploration of the efficacy of this trigger in other PLP-enzyme active sites.
Oxidation of oximes to nitrile oxides with hypervalent iodine reagents
Mendelsohn, Brian A.,Lee, Shelley,Kim, Simon,Teyssier, Florian,Aulakh, Virender S.,Ciufolini, Marco A.
supporting information; experimental part, p. 1539 - 1542 (2009/08/07)
Iodobenzene diacetate in MeOH containing a catalytic amount of TFA efficiently oxidizes aldoximes to nitrile oxides. The latter may be trapped in situ with olefins in a bimolecular or an intramolecular mode. The new method enables the execution of tandem oxidative dearomatization of phenols/intramolecular nitrile oxide cycloaddition sequences leading to useful synthetic intermediates.
Facile synthesis of highly functionalized N-methyl amino acid esters without side-chain protection
White, Kimberly N.,Konopelski, Joseph P.
, p. 4111 - 4112 (2007/10/03)
(Chemical Equation Presented) The facile, two-pot synthesis of N-methyl amino acid esters by way of reductive amination is presented. Side chain protection schemes are not required, the starting materials are all commercially available, and the synthetic
Synthesis of methyl esters of N-(O, O-diethyl-phosphonobenzyl)-2-amino-3-aryl-propanoic acid
Tchapkanov, Atanas,Petrov, Galin
, p. 45 - 50 (2007/10/03)
Methyl esters of N-(O,O-diethylphosphonobenzyl-)-2-amino-3-aryl-propanoic acid were synthesized by the addition of diethylphosphite to Schiff hases of 2-amino carboxylic acids (L-phenyl-alanine and L-tyrosine). The compounds were obtained as a mixture of σ-diastereoisomers and the structures were confirmed by spectral methods.
Direct synthesis of 3-fluoro-α-fluoromethyl-p-tyrosine
DeJusus, O. T.,Murali, D.,Kitchen, R.,Oakes, T. R.,Nickles, R. J.
, p. 73 - 78 (2007/10/02)
3-Fluoro-α-fluoromethyl-p-tyrosine was synthesized directly by the reaction of acetyl hypofluorite with α-fluoromethyl-p-tyrosine. α-Fluoromethyl-p-tyrosine was prepared by a four-step reaction while acetyl hypofluorite was prepared from elemental fluorin
