147489-27-8Relevant academic research and scientific papers
An improved, scalable synthesis of bis-amino acids
Cheong, Jae Eun,Pfeiffer, Conrad T.,Northrup, Justin D.,Parker, Matthew F.L.,Schafmeister, Christian E.
supporting information, p. 4882 - 4884 (2016/10/24)
trans-4-Hydroxy-L-proline derived bis-amino acids are chiral, cyclic building blocks that display two alpha-amino acids that are differentiated from each other with protecting groups. They are assembled into spiroligomers—rigid, shape-programmable spirocyclic oligomers that are both stereochemically and functionally diverse. The synthesis presented here focuses on recent improvements that allow for a convenient, large-scale synthesis of twelve stereochemically pure bis-amino acids from inexpensive trans-4-hydroxy-L-proline. The bis-amino acids differ in stereochemistry as well as the amine protecting group, one of which (para-nitrobenzyl carbamate) has not been previously incorporated into bis-amino acids.
Synthesis and evaluation of conformationally restricted inhibitors of aspartate semialdehyde dehydrogenase
Evitt, Andrew S.,Cox, Russell J.
scheme or table, p. 1564 - 1575 (2012/03/27)
Inhibitors of the enzyme aspartate semialdehyde dehydrogenase, a key biological target for the generation of a new class of antibiotic compounds, have been developed. To investigate improvements to binding within an inhibitor series, the lowering of the entropic barrier to binding through conformational restriction was investigated. A library of linear and cyclic substrate analogues was generated and computational docking used to aid in structure selection. The cyclic phosphonate inhibitor 18 was thus identified as complimentary to the enzyme active-site. Synthesis and in vitro inhibition assay revealed a K i of 3.8 mM against natural substrate, where the linear analogue of 18, compound 15, had previously shown no inhibitory activity. Two further inhibitors, phosphate analogue diastereoisomers 17a and 17b, were synthesised and also found to have low millimolar Ki values. As a result of the computational docking investigations, a novel substrate binding interaction was discovered: hydrogen bonding between the substrate (phosphate hydroxy-group as the hydrogen bond donor) and the NADPH cofactor (2′-oxygen as the hydrogen bond acceptor). The Royal Society of Chemistry 2011.
Convenient synthesis and evaluation of biological activity of benzyl (2S)-2-[(R)-1-hydroxy-2-oxo-(1-phenethyl)prop-3-ylcarbamoyl]-4-oxopiperidine- (or -4-oxopyrrolidine)-1-carboxylate as novel histone deacetylase inhibitors
Oh, Seikwan,Moon, Hyung-In,Jung, Jae-Chul
scheme or table, p. 1300 - 1304 (2009/06/20)
A simple synthesis, involving a key coupling reaction, and the biological activity of the title compounds 16 and 17 are described. The key fragments are the amine·HCl salt 6 and the acids 9 and 13, which were smoothly coupled by using ethyl(dimethylaminopropyl)carbodiimide (EDCI) and 1- hydroxybenzotriazole (HOBt) in high yield. We have found that the in vitro growth inhibitory potency of the new compounds 16 and 17 exhibits good histone deacetylase (HDAC) activity.
Diastereoselective synthesis of (2S,5S)- and (2S,5R)-N-benzyloxycarbonyl-5-hydroxypipecolic acids from trans-4-hydroxy-l-proline
Jung, Jae-Chul,Avery, Mitchell A.
, p. 2479 - 2486 (2007/10/03)
An efficient diastereoselective synthesis of cis- and trans-5-hydroxy-(2S)-N-benzyloxycarbonyl pipecolic acids, starting from trans-4-hydroxy-l-proline is described. The key synthetic strategies involve the regioisomeric ring expansion of keto ester 8 and diastereoselective reduction of ketone 11 in high selectivity and yield.
Bis (amino acid) molecular scaffolds
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Page 13, (2010/02/06)
The present invention provides molecular building blocks of rigid bis(amino acids). The molecular building blocks can be linked together through the formation of rigid diketopiperazine rings, to provide the desired three dimensional structure. Also provided is method of synthesizing macromolecules from the bis (amino acid) building blocks.
Restriction of a Peptide Turn Conformation and Conformational Analysis of Guanidino Group Using Arginine-Proline Fused Amino Acids: Application to Mini Atrial Natriuretic Peptide on Binding to the Receptor
Sugase, Kenji,Horikawa, Manabu,Sugiyama, Masako,Ishiguro, Masaji
, p. 489 - 492 (2007/10/03)
Compounds (2S,4S)- and (2S,4R)-4-(2′-guanidinoethyl)proline have been synthesized as a conformationally restricted arginine, Their backbones fit the i + 1 position in a turn, and the side chains are restricted compared to that of arginine. These analogues were incorporated into mini atrial natriuretic polypeptide, which has an important turnlike conformation at Gly6-Arg7-Met8-Asp9. Structural analysis revealed that the size of the conformational space of Arg7 on binding to the receptor was approximately one-third of the entire conformational space.
The synthesis of functionalized nanoscale molecular rods of defined length
Levins, Christopher G.,Schafmeister, Christian E.
, p. 4702 - 4703 (2007/10/03)
We report a synthetic approach to spiro-ladder oligomers of defined length and structure that form water-soluble molecular rods. We describe the synthesis of a chiral molecular building block 1 and its assembly on solid support to form flexible chains that were then rigidified by the parallel formation of several diketopiperazine rings. Two molecular rods approximately 15 and 25 A in length were synthesized containing three and five monomers, respectively. The molecular rods were easily functionalized on both ends and were shown to have high water solubility, making them compatible with biological buffers. These molecules may find use as scaffolds for the display of ligands in chemical-biology applications and as spacers and construction materials for nanoscience applications. Copyright
Stereoselective synthesis of novel chimerical amino acids via a photochemical key step
Wessig, Pablo
, p. 1465 - 1467 (2007/10/03)
The synthesis of novel chimerical amino acid derivatives 6-8 bearing the 6-azatricyclo[3.3.1.033,7]nonane (methanotropane) skeleton is described. Starting with one chirality centre in L-4-oxoprolines 2 we succeeded in the fully stereoselective introduction of four new chirality centres. The key step of our synthetic route is a photochemical cyclization of phenyl ketones, whose stereoselectivity has been explained by the different stability of the triplet biradical conformers.
The synthesis of bicyclic proline derivatives with 1,4N-lactam grouping
Yelin,Onoprienko
, p. 594 - 598 (2007/10/03)
The N-benzyloxycarbonyl-4-oxoproline ferr-butyl ester prepared from trans-4-hydroxy-L-proline was shown to be capable of a reductive amination with esters of α- or β-amino acids to the corresponding (45)-4-aminoderivatives. One of the resulting products, (45)-4-glycinoderivative, was easily cyclized after selective removal of the acid-labile protective group. There resulted bridge bicyclic synthons suitable for peptide synthesis: (2S,5S)-benzyloxycarbonyl-4-methoxycarbonylmethyl-3-oxo-1,4-diazabicyclo[2.2.1] heptane, (2S,5S)-1-(9-fluorenylmethoxycarbonyl-4-methoxycarbonyl-3-oxo-1,4- diazabicyclo[2.2.1 ]heptane, and (2S,5S)-1-(9-fluorenylmethoxycarbonyl-4-carboxymethyl-3-oxo-l,4-diazabicyclo[2. 2.1]heptane. Their possible use for the study of biologically significant conformations of bioactive proline-containing oligopeptides is discussed.
