- Green preparation method of N-substituted-L-pyroglutamate
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The invention provides a green preparation method of N-substituted-L-pyroglutamate. The method comprises the steps as follows: L-glutamic acid diester hydrochloride (III) is prepared from L-glutamic acid (II) as a starting material in the presence of an acidic reagent by an esterification reaction; then, L-glutamic acid diester hydrochloride (III) is subjected to N-substituted protective reactionwith an N-substituent protective reagent with a one-pot method in the presence of a base and a solvent, an N-substituted protective group is introduced, heating is performed for dealcoholization cyclization in molecules, and N-substituted-L-pyroglutamate as shown in the formula (I) is obtained. The method has the advantages of cheap and easily available raw materials, classic reaction types, shortprocess route, simple and convenient operation, small waste water amount, green and environment-friendly production process, high reaction yield and low product cost. 5R-benzyloxyaminopiperidine-2S-carboxylate, 5R-benzyloxyaminopiperidine-2S-formate ethanedioate and avibactam can be prepared from N-substituted-L-pyroglutamate as shown in the formula (I).
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Paragraph 0063; 0064
(2018/03/28)
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- Synthesis of highly functionalized 2,5-disubstituted pyrrolidines via an aza-Morita-Baylis-Hillman-type reaction
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An aza-Morita-Baylis-Hillman-type reaction of Michael acceptors with 5-substituted cyclic N,O-acetals derived from pyrrolidines has been investigated. It has been found that the combination of Me2S and TMSOTf work well with unhindered and reactive enals and enones whilst the use of quinuclidine and TMSOTf is superior for more hindered Michael acceptors. The reactions lead to 2,5-trans-disubstituted pyrrolidines with good to excellent diastereoselectivity. The origin of the selectivity is discussed.
- Kitulagoda, James E.,Palmelund, Anders,Aggarwal, Varinder K.
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supporting information; experimental part
p. 6293 - 6299
(2010/10/19)
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- Synthesis of Two Stable Nitrogen Analogues of S-Adenosyl-L-methionine
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Homochiral syntheses of two stable nitrogen analogues of S-adenosyl-L-methionine (AdoMet) are described. In the first analogue, AzaAdoMet, the sulfonium center of AdoMet, is replaced by an N-methyl moiety whose pKa is 7.08. This provides a char
- Thompson, Mark J.,Mekhalfia, Abdelaziz,Hornby, David P.,Blackburn, G. Michael
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p. 7467 - 7473
(2007/10/03)
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- Amino acids and peptides. XLIX. Synthesis of γ-2-adamantylglutamate and its evaluation for peptide synthesis
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2-Adamantyl ester was examined for the selective protection of the γ- carboxyl function of the Glu residue, with the aim of preventing side reactions during peptide synthesis and increasing the solubility in organic solvents of peptide intermediates containing the Glu residue. Z-Glu(O-2- Ada)-OBzl was synthesized from Z-Glu-OBzl and adamantan-2-ol with the aid of dicyclohexylcarbodiimide (DCC) and 4-N,N-dimethylaminopyridine (DMAP) in AcOEt. The 2-adamantyl ester group was stable to TFA, 20% piperidine/DMF and 10% Et3N/DMF up to 24 h and was easily removed by MSA, 1 M TFMSA-thioanisole in TFA, and HF. Therefore, H-Glu-(O-2-Ada)-OH could be applied for peptide synthesis in both solution and solid phase methods in combination with a Boc or Fmoc group as the N2-protecting group. Boc-Glu(O-2-Ada)-OH was successfully employed for the synthesis of Bz-Ile-Glu-Gly-Arg-CH2Cl, an irreversible inhibitor of factor Xa.
- Okada, Yoshio,Mu
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- Stereospecific synthesis of (2S,4R)-[5,5,5-2H3]leucine
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The first stereospecific chemical synthesis of a sample of the amino acid (2S)-leucine labelled in one of the diastereotopic methyl groups has been achieved using (2S)-pyroglutamic acid as a chiral template. This has been used to develop a method for assigning resonances to the diastereotopic methyl groups of the leucine residues in the 1H NMR spectra of proteins.
- August, Ryan A.,Khan, Jeffrey A.,Moody, Claire M.,Young, Douglas W.
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p. 507 - 514
(2007/10/03)
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- A convenient N-protection of pyroglutamate derivatives
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Esters of pyroglutamic acid were N-protected by conventional protective groups (Z. Boc, and COOMe) in high yield, without racemization, using LiHMDS in THF at -78°C and ZCl, Boc2O, and ClCOOMe, respectively.
- Li,Sakamoto,Kato,Kikugawa
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p. 4045 - 4052
(2007/10/03)
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- Amino Acid Synthesis Using (L)-Pyroglutamic Acid as a Chiral Starting Material
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Deprotonation of protected pyroglutamates 1(c), 1(d), and 1(e) with lithium di-isopropylamine (LDA) or lithium hexamethyldisilazide (LiHDMS) in THF, followed by reaction with electrophiles, leads to the formation of 4-substituted pyroglutamates in good yield.This approach has been used for the synthesis of the novel amino acid (4).Key Words: pyroglutamic acid; chiral amino acid synthesis
- Baldwin, Jack E.,Miranda, Tania,Moloney, Mark,Hokelek, Tuncer
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p. 7459 - 7468
(2007/10/02)
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