1948-48-7Relevant academic research and scientific papers
Chiral β-lactam-based integrin ligands through Lipase-catalysed kinetic resolution and their enantioselective receptor response
Martelli, Giulia,Galletti, Paola,Baiula, Monica,Calcinari, Luca,Boschi, Giacomo,Giacomini, Daria
, (2019/05/17)
Obtainment and testing of pure enantiomers are of great importance for bioactive compounds, because of the assessed implications of enantioselectivity in receptor-mediated responses. Herein we evaluated the use of biocatalysis to obtain enantiomerically pure β-lactam intermediates further exploited in the synthesis of novel integrin ligands as single enantiomers. From a preliminary screening on a set of commercially available hydrolases, Burkholderia Cepacia Lipase (BCL)emerged as a suitable and highly performing enzyme for the kinetic resolution of a racemic azetidinone, key intermediate for the synthesis of novel agonists of integrins. Upon optimization of the biocatalytic protocol in terms of enzymes, acylating agents and procedures, the two β-lactam enantiomers were obtained in excellent enantiomeric excesses (94% and 98% ee). Synthetic elaborations on the separated enantiomers allowed the synthesis of four chiral β-lactams which were evaluated in cell adhesion assays on Jurkat cell line expressing α4β1 integrin, and K562 cell line expressing α5β1 integrin. Biological tests revealed that only (S)-enantiomers maintained the agonist activity of racemates with a nanomolar potency, and a specific enantio-recognition by integrin receptors was demonstrated.
Polypeptide formation by heating N-t-butyloxycarbonyl acidic amino acid derivatives
Munegumi,Qing Meng,Harada
, p. 4716 - 4722 (2014/12/10)
An acid labile N-protecting group for amino acids, t-butyloxycarbonyl (Boc) group has deprotected at elevated temperatures. The study describes an application of the lability on heating to synthesis of polypeptides from acidic amino acids. t-Butyloxycarbonyl-acidic amino acids (aspartic acid, glutamic acid and β-aminoglutaric acid) and their anhydrides were heated at the higher temperatures than their melting points. Anhydrides of t-butyloxycarbonyl-aspartic acid and t-butyloxycarbonyl-β-aminoglutaric acid gave polypeptides. Thermal analyses of the substrates clarified the pathway of the polypeptide formation.
Syntheses of Polypeptides by Hidrogenolysis of N-Benzyloxycarbonyl-Amino Acid Anhydrides
Munegumi, Toratane,Meng, Yan-Quing,Harada, Kaoru
, p. 2748 - 2750 (2007/10/02)
When anhydrides of N-benzyloxycarbonyl-DL-aspartic acid (Z-DL-Asp), Z-L-Asp, N-Z-DL-glutamic acid (Z-DL-Glu), Z-L-Glu and N-Z-3-aminoglutaric acid (Z-β-Agl) were hydrogenolyzed in N,N-dimethylformamide (DMF), polypeptides were obtained in high yields.Hydrogenolyses of Z-DL-Glu and Z-L-Glu in dioxane gave pyroglutamic acid.
Thermal Syntheses of Polypeptides from N-Boc-Amino Acid(Aspartic Acid,β-Aminoglutaric Acid) Anhydrides
Munegumi, Toratane,Meng, Yan-Quing,Harada, Kaoru
, p. 1643 - 1646 (2007/10/02)
N-t-Butyloxycarbonyl-amino acid(aspartic acid:Asp, glutamic acid:Glu, β-aminoglutaric acid: β-Agl)anhydrides were deprotected upon heating at temperatures slightly higher than the melting points of these compounds and polypeptides were synthesized easily in high yield.
