New Proline–Oxazoline Ligands and Their Application in the Asymmetric Nozaki–Hiyama–Kishi Reaction

Hargaden, Gráinne C.; Müller‐Bunz, Helge; Guiry, Patrick J.

doi:10.1002/ejoc.200700227

Cited by 48 publications

(10 citation statements)

References 36 publications

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“…However, this resulted in a very low yield of the desired product 5 (4%). The monofluoro- and trifluoroethyl esters 3 and 5 were then prepared via the corresponding chloranhydride, which was generated as described ( Scheme 1 ) [ 51 ]. The drawback of this method is that generation of chloranhydride from N -acetylated proline leads to partial epimerization of the residue.…”

Section: Resultsmentioning

confidence: 99%

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

Kubyshkin

Budiša

2017

Beilstein J. Org. Chem.

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Fluorinated moieties are highly valuable to chemists due to the sensitive NMR detectability of the 19F nucleus. Fluorination of molecular scaffolds can also selectively influence a molecule’s polarity, conformational preferences and chemical reactivity, properties that can be exploited for various chemical applications. A powerful route for incorporating fluorine atoms in biomolecules is last-stage fluorination of peptide scaffolds. One of these methods involves esterification of the C-terminus of peptides using a diazomethane species. Here, we provide an investigation of the physicochemical consequences of peptide esterification with partially fluorinated ethyl groups. Derivatives of N-acetylproline are used to model the effects of fluorination on the lipophilicity, hydrolytic stability and on conformational properties. The conformational impact of the 2,2-difluoromethyl ester on several neutral and charged oligopeptides was also investigated. Our results demonstrate that partially fluorinated esters undergo variable hydrolysis in biologically relevant buffers. The hydrolytic stability can be tailored over a broad pH range by varying the number of fluorine atoms in the ester moiety or by introducing adjacent charges in the peptide sequence.

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Section: Resultsmentioning

confidence: 99%

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

Kubyshkin

Budiša

2017

Beilstein J. Org. Chem.

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“…EDCI.HCl and HOBt 22 were also tried in the coupling reaction, but produced only trace amounts of the desired product. Ultimately, Cbz-proline was treated with thionyl chloride 23 to produce the acid chloride which was then reacted with amine 7 in the presence of triethylamine in DCM to afford amide 8 in 50% yield. Compound 8 was then treated with TBAF in THF remove the TBDMS group, 24 generating alcohol 9 in 64% yield.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide

Racys¹,

Rea²,

Fülöp³

et al. 2010

Bioorganic & Medicinal Chemistry

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The synthesis of a new inhibitor of prolyl oligopeptidase, containing a piperidine ring, together with an X-ray structure of its complex with the enzyme, is described. This provides evidence that covalent inhibitors of POP do not have to be limited to structures containing 5-membered N-containing heterocyclic rings. inhibitor:Leave this area blank for abstract info. Abstract-A new inhibitor, containing a linked proline-piperidine structure, for the enzyme prolyl oligopeptidase (POP) has been synthesised and demonstrated to bind covalently with the enzyme at the active site. This provides evidence that covalent inhibitors of POP do not have to be limited to structures containing 5-membered N-containing heterocyclic rings.

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“…Guiry and co-workers have also observed the presence of two distinct NH peaks in a similar ligand framework. 27 At elevated temperature (30°C), these peaks coalesced to a single resonance, which is attributed to the presence of rotamers resulting from hindered rotation. When ligand L1 was subjected to the VT-NMR experiment in the range of 0-55°C, however, no obvious shift or coalescence was observed, suggesting the presence of a mixture of diastereomers resulting from minor racemization.…”

Section: S Omentioning

confidence: 97%

Modular Synthesis of Chiral β-Diketiminato-Type Ligands Containing 2-Oxazoline Moiety via Palladium-Catalyzed Amination

Binda¹,

Abbina²,

Du³

2011

Synthesis

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A family of new chiral b-diketiminato-type ligands containing oxazoline moiety has been synthesized in moderate to high yields (typically 30-95%) via a Pd-catalyzed amination reaction of chiral oxazolines with primary amines and amides. Notably, (S)-tert-butylsulfinamide was successfully incorporated into the ligand framework as a coupling partner in amination. Due to the readily available pool of chiral building blocks, this represents a facile and modular approach for synthesizing libraries of novel chiral bdiketiminato-type ligands, with potential applications in asymmetric catalysis.Because the reactivity and selectivity of metal catalysts are largely determined by the auxiliary ligands, ligand design has been a central theme in catalysis, particularly in asymmetric synthesis, which continues to be of great academic and industrial importance. 1 One of the challenges is to derive efficient chiral catalysts for asymmetric induction in different substrates with subtle variations. Since it is not expected that a single catalyst will work for a wide range of substrates, an efficient strategy towards new catalysts would be the design of a search pathway that provides access to a large number of structurally similar ligands with tunable yet diverse substituents. 2 Indeed, many researchers have sought to develop asymmetric catalysts by screening a large pool of chiral ligands. 3 To this end, a modular approach for the ligand library construction is highly desirable. 4 b-Diketiminato ligands ( Figure 1A) have received great attention in coordination chemistry due to the ease of fine tuning of the steric and electronic properties. 5 These ligands are monoanionic upon deprotonation and form strong bonds with metals, usually in a bidentate fashion. Various b-diketiminato metal complexes have been employed in a number of catalytic reactions. 6,7 In a broader sense, the monoanionic, anilinido-imino ligands ( Figure 1B) can be included as a variation of the regular b-diketiminato framework. 8 One example is the ortho-oxazoline-substituted anilines, in which aniline nitrogens are typically not further functionalized. 9 Due to the presence of an aromatic ring, the resonance in the backbone is attenuated in comparison with the regular ligands and this may offer opportunity for electronic differentiation and stereocontrol upon coordination. 10 Given their extensive applications, it is somewhat surprising that the chiral variants of b-diketiminato ligands are relatively less developed in the literature, 11,12 although these moieties are often incorporated as subcomponents of multidentate or macrocyclic ligands in chiral environments. 13 In principle, stereo-directing groups can be introduced into all the R 1 -R 5 substituents. Of particular interest are ligands with chiral substituents at the periphery (R 1 and R 5 ) that are in close proximity with the open coordination site where catalysis is taking place. Among these, monoanionic, chiral semicorrin 14 and bisoxazoline ligands 15 are some of the successful examples, where chir...

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New Proline–Oxazoline Ligands and Their Application in the Asymmetric Nozaki–Hiyama–Kishi Reaction

Cited by 48 publications

References 36 publications

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

Inhibition of prolyl oligopeptidase with a synthetic unnatural dipeptide

Modular Synthesis of Chiral β-Diketiminato-Type Ligands Containing 2-Oxazoline Moiety via Palladium-Catalyzed Amination

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