153077-03-3Relevant academic research and scientific papers
Efficient access to enantiopure γ4-amino acids with proteinogenic side-chains and structural investigation of γ4- asn and γ4-ser in hybrid peptide helices
Jadhav, Sandip V.,Misra, Rajkumar,Singh, Sumeet K.,Gopi, Hosahudya N.
, p. 16256 - 16262 (2013/12/04)
Hybrid peptides composed of α- and β-amino acids have recently emerged as new class of peptide foldamers. Comparatively, γ- and hybrid γ-peptides composed of γ4-amino acids are less studied than their β-counterparts. However, recent investigations reveal that γ4-amino acids have a higher propensity to fold into ordered helical structures. As amino acid side-chain functional groups play a crucial role in the biological context, the objective of this study was to investigate efficient synthesis of γ4-residues with functional proteinogenic side-chains and their structural analysis in hybrid-peptide sequences. Here, the efficient and enantiopure synthesis of various N- and C-terminal free-γ4-residues, starting from the benzyl esters (COOBzl) of N-Cbz-protected (E)-α,β-unsaturated γ-amino acids through multiple hydrogenolysis and double-bond reduction in a single-pot catalytic hydrogenation is reported. The crystal conformations of eight unprotected γ4-amino acids (γ4-Val, γ4-Leu, γ4-Ile, γ4-Thr(OtBu), γ4-Tyr, γ4-Asp(OtBu), γ4- Glu(OtBu), and γ-Aib) reveals that these amino acids adopted a helix favoring gauche conformations along the central Cγi￡ Cβ bond. To study the behavior of γ4- residues with functional side chains in peptide sequences, two short hybrid γ-peptides P1 (Ac-Aib-γ4-Asn-Aib-γ4-Leu- Aib-γ4-Leu-CONH2) and P2 (Ac-Aib- γ4-Ser-Aib-γ4-Val-Aib-γ4-Val- CONH2) were designed, synthesized on solid phase, and their 12-helical conformation in single crystals were studied. Remarkably, the γ4-Asn residue in P1 facilitates the tetrameric helical aggregations through interhelical H bonding between the side-chain amide groups. Furthermore, the hydroxyl side-chain of γ4-Ser in P2 is involved in the interhelical H bonding with the backbone amide group. In addition, the analysis of 87 γ4-residues in peptide single-crystals reveal that the γ4-residues in 12-helices are more ordered as compared with the 10/12- and 12/14-helices. Copyright
Pyrazine alkaloids via dimerization of amino acid-derived α-amino aldehydes: Biomimetic synthesis of 2,5-diisopropylpyrazine, 2,5-bis(3- indolylmethyl)pyrazine and actinopolymorphol C
Badrinarayanan, Sandhya,Sperry, Jonathan
, p. 2126 - 2132 (2012/04/23)
The dimerization of amino acid-derived α-amino aldehydes provides a short, biomimetic synthesis of several 2,5-disubstituted pyrazine natural products. The α-amino aldehyde intermediates were generated in situ by the hydrogenolysis of their Cbz-derivative
HYDROXYMORPHOLINONE DERIVATIVE AND MEDICINAL USE THEREOF
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Page 18, (2010/02/09)
A compound represented by the following formula (I) wherein R1 and R2 are each a lower alkyl group optionally having substituents, which has a calpain inhibitory activity, or a salt thereof is provided.
Novel 6-Hydroxy-3-morpholinones as cornea permeable calpain inhibitors
Nakamura, Masayuki,Miyashita, Hiroyuki,Yamaguchi, Masazumi,Shirasaki, Yoshihisa,Nakamura, Yoshikuni,Inoue, Jun
, p. 5449 - 5460 (2007/10/03)
A novel series of 6-hydroxy-3-morpholinones, in which the functional aldehyde and the hydroxy group of P2 site form a cyclic hemiacetal, was identified as calpain inhibitors. The placement of isobutyl group at the 2-position of the 3-morpholino
A concise synthesis of the novel antibiotic aranorosin
McKillop,McLaren,Watson,Taylor,Lewis
, p. 5519 - 5522 (2007/10/02)
A short synthesis of the novel antibiotic aranorosin is described which employs a novel hypervalent iodine-mediated oxidative hydroxylation of a tyrosinal derivative in the key step. A similar procedure was employed to prepare 6'-epiaranorosin, and hence establish the stereochemistry of the natural compound.
