92086-93-6Relevant academic research and scientific papers
A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives
Watson, Morag E.,Jamieson, Craig,Kennedy, Alan R.,Mason, Andrew M.
, (2019/08/08)
α,α-Disubstituted alkenyl amino acid derivatives (e.g. Fmoc-S5-OH) are valuable monomers in the construction of stapled peptide derivatives. Synthetic access to these is possible using the Ni-[(Benzylprolyl)amino]benzophenone (BPB) complex as a chiral auxiliary. We discuss a reappraisal of the use of this, and demonstrate that epimerisation of the proline α-centre occurs during formation of the complex, leading to erosion in the enantiomeric excess of the final product. Modified conditions have been developed, providing the target compounds in high enantiomeric excess.
Total synthesis of the cyclic depsipeptide YM-280193, a platelet aggregation inhibitor
Kaur, Harveen,Harris, Paul W. R.,Little, Peter J.,Brimble, Margaret A.
supporting information, p. 492 - 495 (2015/03/05)
The first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the ADP-induced aggregation of human platelets, is described. The monomer and dipeptide fragments were prepared using conventional chemistry and subsequently assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel bis-alkylation-elimination of cysteine on-resin was employed to introduce the unnatural N-methyldehydroalanine moiety. The final step involved execution of a key macrolactamization reaction between the hindered unnatural N,O-dimethylthreonine and ?2-hydroxyleucine residues.
A Convenient Method for the Asymmetric Synthesis of Fluorinated α-Amino Acids from Alcohols
Drouet, Fleur,Noisier, Anas F. M.,Harris, Craig S.,Furkert, Daniel P.,Brimble, Margaret A.
supporting information, p. 1195 - 1201 (2015/10/05)
Due to their numerous applications, fluorinated amino acids have recently attracted significant attention. The preparation of fluorine-containing phenylalanines, heteroaryl alanines and aliphatic fluorinated amino acids using Mitsunobu-Tsunoda alkylation of a chiral nucleophilic glycine equivalent with readily available alcohol substrates is described. The reaction proceeds in high yields and with excellent diastereoselectivity. This method provides an efficient synthetic route to fluorinated amino acids for which asymmetric approaches are scarce.
Synthesis of methyl N-Boc-(2 S,4 R)-4-methylpipecolate
Hung, Kuo-Yuan,Harris, Paul W. R.,Brimble, Margaret A.
supporting information; experimental part, p. 8728 - 8731 (2011/02/26)
An efficient stereoselective synthesis of fully protected (2S,4R)-4-methylpipecolic acid has been developed. The synthesis was achieved by initial asymmetric α-alkylation of glycine with a chiral iodide, affording the linear precursor as a single stereoisomer. Subsequent aldehyde formation using OsO4/NaIO4 followed by immediate intramolecular cyclization afforded an enamine that was then subjected to hydrogenation to give the final compound in 23% yield over 10 steps.
A One-Pot approach to neoglycopeptides using orthogonal native chemical ligation and click chemistry
Lee, Dong Jun,Mandai, Kalyaneswar,Harris, Paul W. R.,Brimble, Margaret A.,Kent, Stephen B. H.
supporting information; experimental part, p. 5270 - 5273 (2009/12/28)
The powerful combination of native chemical ligation and click chemistry has been used to affect a one-pot synthesis of neogiycopeptiaes from propargyl-containing peptides using GaINAc-N3 as the glycan component. A versatile chemical toolkit fo
General Method of Diastereo- and Enantioselective Synthesis of β-Hydroxy-α-amino Acids by Condensation of Aldehydes and Ketones with Glycine
Belokon, Yuri N.,Bulychev, Alexander G.,Vitt, Sergei V.,Struchkov, Yuri T.,Batsanov, Andrei S.,et al.
, p. 4252 - 4259 (2007/10/02)
The condensation of formaldehyde with a Ni(II) complex of glicyne Schiff base with (S)-2-acetophenone (1) or (S)-2-benzophenone (2) in CH3OH at 25 deg C in the presence of Et3N yields (S)-Ser with an enantiomeric excess (ee) of 80-90percent.The same reaction gives rise to (R)-Ser with an ee greater than 80percent in the presence of more than 0.2 N CH3ONa, α-(hydroxymethyl) serine being formed in negligible quantities.The reaction of benzaldehyde, 3,4-(methilenedioxy)benzaldehyde, and acetaldehyde with these Gly complexes in 0.2 N CH3ONa at 25 deg C yields β-hydroxy-α-amino acids: (R)-β-phenylserine, (R)-3,4-(methylenedioxy)-β-phenylserine, and (R)-threonine, respectively, with a threo/allo ratio ranging from 10:1 up to over 50:1 and ee more than 80percent.Condensation with acetone yields (R)-β-hydroxyvaline with an enantiomeric purity of 70percent.The enantiomerically pure β-hydroxy-α-amino acids can be obtained from pure diastereomers, isolated by chromatography on silica or Toyopearl HW-60.The initial reagents 1 and 2 were recovered with 60-98percent yield.The stereochemical mechanism of the reaction is discussed.
