Synthesis of unusual isoxazoline containing<b>β</b>and<b>γ</b>-dipeptides as potential glutamate receptor ligands

Tamborini, Lucia; Mastronardi, Federica; Dall’Oglio, Federica; Micheli, Carlo De; Nielsen, Birgitte; Presti, Leonardo Lo; Conti, Paola; Pinto, Andrea

doi:10.1039/c5md00159e

Cited by 6 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two enantiomers of compound 1 were obtained starting from the corresponding ethyl esters recently described by us (Tamborini et al, 2015 ). Racemate (±)- 2 (Conti et al, 2006 ) was synthesized in a flow chemistry reactor exploiting the 1,3-dipolar cycloaddition reaction of N -Boc-3-pyrroline with ethoxycarbonyl formonitrile oxide.…”

Section: Resultsmentioning

confidence: 99%

“…In this work, we investigated the conformational behavior of both the enantiomers of the bicyclic unnatural γ amino acid 4,5,6,6a-tetrahydro-3a H -pyrrolo[3,4- d ]isoxazole-3-carboxylic acid 1 , obtained starting from the corresponding ethyl esters recently described by us (Tamborini et al, 2015 ). Compound 1 is a conformationally constrained dipeptide analog and, in principle, it could substitute two amino acids in a peptide chain.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides

et al. 2019

Self Cite

View full text Add to dashboard Cite

Unnatural amino acids have tremendously expanded the folding possibilities of peptides and peptide mimics. While α,α-disubstituted and β-amino acids are widely studied, γ-derivatives have been less exploited. Here we report the conformational study on the bicyclic unnatural γ amino acid, 4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]isoxazole-3-carboxylic acid 1. In model peptides, the (+)-(3aR6aS)-enantiomer is able to stabilize α-turn conformation when associated to glycine, as showed by 1H-NMR, FT-IR, and circular dichroism experiments, and molecular modeling studies. α-turn is a structural motif occurring in many biologically active protein sites, although its stabilization on isolated peptides is quite uncommon. Our results make the unnatural γ-amino acid 1 of particular interest for the development of bioactive peptidomimetics.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The enatiomeric mixture was separated using Chiral Semi-Preparative-HPLC. [34] Each enantiomer was then inserted into model peptides. NMR, FT-IR, CD and molecular modeling studies indicated that the dipeptide Gly/(+)-36 is able to stabilize a αturn conformation, due to H-bond between C=O Gly (i) and NH of amide protecting group (i + 4).…”

Section: Gamma Aasmentioning

confidence: 99%

Fishing in the Toolbox of Cyclic Turn Mimics: a Literature Overview of the Last Decade

et al. 2021

View full text Add to dashboard Cite

Dedicated to Prof. Franco Cozzi for its 70th birthday.The main goal in developing peptidomimetics is the stabilization of the bioactive conformation of peptides. Among all the secondary structures, turns are of paramount importance. This review highlights the recent advances in the design and synthesis of cyclic turn mimics. Both amino acids, carbo-and hetero-cyclic scaffolds have been considered, focusing on their use in the preparation of peptidomimetics and on their ability to induce γ-, β-, and α-turns.

show abstract

“…In particular, the 3‐isoxazolidinone scaffold is present in the natural amino acid Tricholomic acid ( 24) and in various derivatives active on the glutamate neurotransmission system ( 25 and 26 , Scheme 10). [52,68,95–99] …”

Section: Reactivity Of 3‐bromo‐45‐dihydroisoxazolesmentioning

confidence: 99%

“…Moreover, the replacement of bromine with hydroxy or alkoxy moieties has been employed for the synthesis of Muscarone analogues, [78] neuroactive molecules [70,100–102] and antiparasitic compounds [18] . Aliphatic alcohols can be easily converted in situ in the corresponding alkoxy anions, using a base such as K 2 CO 3 , [18,70,79,82,102] Cs 2 CO 3 [88,103] or NaH [31,97,101,102] . These alkoxy species are nucleophilic enough to attack the C3 carbon and displace the bromine to give the 3‐alkoxy‐Δ 2 ‐isoxazolines.…”

Section: Reactivity Of 3‐bromo‐45‐dihydroisoxazolesmentioning

confidence: 99%

Synthesis and Reactivity of 3‐Halo‐4,5‐dihydroisoxazoles: An Overview

Zana

Galbiati

2021

ChemistrySelect

View full text Add to dashboard Cite

The 3‐halo‐4,5‐dihydroisoxazole moiety is an interesting emerging feature in medicinal and organic chemistry fields. The properties of this nucleus are intimately correlated with the nature of the halogen substituent, ranging from inertness to instability. In between, the 3‐bromo‐Δ2‐isoxazoline scaffold stands out as a handleable and easily affordable electrophilic warhead, able to react with nucleophilic active sites of different enzymes, determining inhibitory effects. However, the importance of 3‐bromo‐Δ2‐isoxazolines does not rely only upon their biological activity. In fact, they are valuable synthetic intermediates, presenting a peculiar reactivity spectrum that allows access to useful chemical functions, ranging from variously decorated dihydroisoxazoles to β‐hydroxynitriles, β‐hydroxyesters, and γ‐hydroxyamines. The synthesis of 3‐bromo‐Δ2‐isoxazolines is predominantly based on the 1,3‐dipolar cycloaddition, a pericyclic reaction accompanied by a remarkable regio‐ and stereo‐selectivity. Thus, this intermediate lends itself especially well to the production of complex molecules with regio‐ and stereo‐chemical requirements.

show abstract

Synthesis of unusual isoxazoline containingβandγ-dipeptides as potential glutamate receptor ligands

Abstract: Unconventional beta and gamma dipeptides as tools to investigate the iGluR binding domain.

Cited by 6 publications

References 19 publications

Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides

Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides

Fishing in the Toolbox of Cyclic Turn Mimics: a Literature Overview of the Last Decade

Synthesis and Reactivity of 3‐Halo‐4,5‐dihydroisoxazoles: An Overview

Contact Info

Product

Resources

About