111662-65-8Relevant articles and documents
Enhanced stereoselectivity of a Cu(II) complex chiral auxiliary in the synthesis of Fmoc-L-γ-carboxyglutamic acid
Smith, Daniel J.,Yap, Glenn P.A.,Kelley, James A.,Schneider, Joel P.
, p. 1513 - 1520 (2011/06/20)
L-γ-Carboxyglutamic acid (Gla) is an uncommon amino acid that binds avidly to mineral surfaces and metal ions. Herein, we report the synthesis of N-R-Fmoc-L-γ-carboxyglutamic acid γ, γ0-tert-butyl ester (Fmoc-Gla(OtBu)2-OH), a suitably protected analogue for Fmoc-based solid-phase peptide synthesis. The residue was synthesized using a novel chiral Cu(II) complex, whose structurebased design was inspired by the blue copper protein rusticyanin. The five-coordinate complex is formed by Shiff base formation between glycine and the novel ligand (S)-2-(N-(2-methylthio)benzylprolyl) aminobenzophenone in the presence of copper. Michael addition of di-tert-butyl methylenemalonate to the R-carbon of the glycine portion of the complex occurs in a diastereoselective fashion. The resulting (S,S)-complex diastereomer can be easily purified by chromatography. Metal complex decomposition followed by Fmoc protection affords the enantiomerically pure amino acid. With the use of this novel chiral complex, the asymmetric synthesis of Fmoc-Gla(OtBu)2-OH was completed in nine steps from thiosalicylic acid in 14.5% overall yield.
Design and concise synthesis of fully protected analogues of L-γ-carboxyglutamic acid
Jiang, Sheng,Li, Peng,Lai, Christopher C.,Kelley, James A.,Roller, Peter P.
, p. 7307 - 7314 (2007/10/03)
The design and synthesis of four nonnaturally occurring amino acid analogues of L-γ-carboxyglutamic acid (Gla), appropriately protected for Fmoc-based solid-phase peptide synthesis (SPPS), is described. These amino acids are Bu-Mal 2, BCAH 3, Pen-Mal 4, a
A practical synthesis of fully protected L-γ-carboxyglutamic acid
Jiang, Sheng,Lai, Christopher C.,Kelley, James A.,Roller, Peter P.
, p. 23 - 25 (2007/10/03)
We have developed a new synthetic route for the preparation of Fmoc protected L-γ-carboxyglutamic acid in 60% overall yield (>99% ee) via a six-step synthesis from D-Garner's aldehyde. An aldol condensation and the selective cleavage of the acetonide prot
The synthesis and properties of Gla- and Phe-containing analogues of cyclic RGD pentapeptides
Davies, John S.,Enjalbal, Christine,Nguyen, Corrine,Al-Jamri, Loai,Naumer, Christian
, p. 2907 - 2915 (2007/10/03)
Cyclopentapeptides containing the Arg-Gly-Asp motif have been synthesised using solid-phase assembly of side-chain-protected linear precursors, followed by solution-phase cyclisation. The replacement of the Asp residue by γ-carboxyglutamic acid (Gla) is a novel feature which gives rise to an analogue which inhibits cell adhesion, yet its congeners do not show activity in binding assays with recombinant integrin receptors. NMR techniques support a β/γ-turn conformation in most of the analogues. The Royal Society of Chemistry 2000.
