Synthesis of novel pipecolic acid derivatives: a multicomponent approach from 3,4,5,6-tetrahydropyridines

Maison, Wolfgang; Lützen, Arne; Kosten, Marc; Schlemminger, Imre; Westerhoff, Ole; Martens, Jürgen

doi:10.1039/a905119h

Cited by 26 publications

(16 citation statements)

References 23 publications

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“…Representative examples are reported in Scheme 1.20. On the other hand, when the chirality was present only on the isocyanide no stereoselectivity was observed, as expected [57]. In situ treatment of enamides 54 with an appropriate nucleophile allowed the conversion into the final products.…”

Section: Chiral Cyclic Iminesmentioning

confidence: 58%

Asymmetric Isocyanide‐Based MCRs

Banfi

Basso

Guanti

et al. 2005

Multicomponent Reactions

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Section: Chiral Cyclic Iminesmentioning

confidence: 58%

Asymmetric Isocyanide‐Based MCRs

Banfi

Basso

Guanti

et al. 2005

Multicomponent Reactions

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“…reported an unexpected cleavage of urea‐containing pipecolic acid derivatives. Maison et al 18. proposed a mechanism of cyclohexenamide hydrolysis involving oxazolinium‐5‐one as an intermediate.…”

Section: Resultsmentioning

confidence: 99%

“…[16] Interestingly, electron-donating substituents increased the cleavage rate, whereas electron-withdrawing substituents slowed down the process. The hydrolysis of pipecolic acid derivatives was described by a few authors, [17][18][19][20] of whom Wei et al [17] reported an unexpected cleavage of urea-containing pipecolic acid derivatives. Maison et al [18] proposed a mechanism of cyclohexenamide hydrolysis involving oxazolinium-5-one as an intermediate.…”

Section: Introductionmentioning

confidence: 99%

“…The hydrolysis of pipecolic acid derivatives was described by a few authors, [17][18][19][20] of whom Wei et al [17] reported an unexpected cleavage of urea-containing pipecolic acid derivatives. Maison et al [18] proposed a mechanism of cyclohexenamide hydrolysis involving oxazolinium-5-one as an intermediate. A similar mechanism was recently postulated describing TFA-catalyzed cleavage reaction for peptides containing pipecolic acid residues.…”

Section: Introductionmentioning

confidence: 99%

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A New Highly Versatile Handle for Chemistry on a Solid Support: The Pipecolic Linker

Zajdel

Nomezine

Masurier

et al. 2010

Chemistry A European J

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The design, synthesis, and potential application of the pipecolic linker is presented. This new versatile handle can immobilize primary, secondary, and aromatic amines, as well as alcohols, phenols, and hydrazides, on a solid support. Compared with other linkers, the anchoring step is easy and efficient. The release of final products from the resin proceeds upon acidic treatment with high purities. The pipecolic linker offers the promise of being using in peptide chemistry to produce peptides modified at the N and C terminus, peptidomimetics, as well as small organic molecules.

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“…Replacement of the proline residue by its six-membered analogue, pipecolic acid, has provided valuable insights in peptide folding and bioactive conformations [ 128 – 129 ]. In particular, pipecolic acid derivatives often find their application as β-turn mimetics [ 130 ], and are therefore included in several pharmaceutical compounds such as antipsychotics, anticonvulsants, local anaesthetics or analgesics [ 131 ]. An interesting diastereoselective multicomponent approach towards such six-membered pipecolic acid-based analogues was described by Maison et al [ 128 ] Although this work is closely related to earlier work of Dömling and Ugi [ 129 ], it is an interesting extension of the original protocol.…”

Section: Reviewmentioning

confidence: 99%

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

Koopmanschap¹,

Ruijter²,

Orru³

2014

Beilstein J. Org. Chem.

231

117

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SummaryIn the recent past, the design and synthesis of peptide mimics (peptidomimetics) has received much attention. This because they have shown in many cases enhanced pharmacological properties over their natural peptide analogues. In particular, the incorporation of cyclic constructs into peptides is of high interest as they reduce the flexibility of the peptide enhancing often affinity for a certain receptor. Moreover, these cyclic mimics force the molecule into a well-defined secondary structure. Constraint structural and conformational features are often found in biological active peptides. For the synthesis of cyclic constrained peptidomimetics usually a sequence of multiple reactions has been applied, which makes it difficult to easily introduce structural diversity necessary for fine tuning the biological activity. A promising approach to tackle this problem is the use of multicomponent reactions (MCRs), because they can introduce both structural diversity and molecular complexity in only one step. Among the MCRs, the isocyanide-based multicomponent reactions (IMCRs) are most relevant for the synthesis of peptidomimetics because they provide peptide-like products. However, these IMCRs usually give linear products and in order to obtain cyclic constrained peptidomimetics, the acyclic products have to be cyclized via additional cyclization strategies. This is possible via incorporation of bifunctional substrates into the initial IMCR. Examples of such bifunctional groups are N-protected amino acids, convertible isocyanides or MCR-components that bear an additional alkene, alkyne or azide moiety and can be cyclized via either a deprotection–cyclization strategy, a ring-closing metathesis, a 1,3-dipolar cycloaddition or even via a sequence of multiple multicomponent reactions. The sequential IMCR-cyclization reactions can afford small cyclic peptide mimics (ranging from four- to seven-membered rings), medium-sized cyclic constructs or peptidic macrocycles (>12 membered rings). This review describes the developments since 2002 of IMCRs-cyclization strategies towards a wide variety of small cyclic mimics, medium sized cyclic constructs and macrocyclic peptidomimetics.

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Synthesis of novel pipecolic acid derivatives: a multicomponent approach from 3,4,5,6-tetrahydropyridines

Cited by 26 publications

References 23 publications

Asymmetric Isocyanide‐Based MCRs

Asymmetric Isocyanide‐Based MCRs

A New Highly Versatile Handle for Chemistry on a Solid Support: The Pipecolic Linker

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

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