Design and Synthesis of Cyclic RGD Pentapeptoids by Consecutive Ugi Reactions

Vercillo, Otilie E.; Andrade, Carlos Kleber Z.; Wessjohann, Ludger A.

doi:10.1021/ol702521g

Cited by 111 publications

(79 citation statements)

References 29 publications

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“…A similar approach has recently been used in a sequential Ugi-oligomerization/Ugi-macrocyclization to produce RGDcyclopentapeptoids. 64 The second appearance of a double-Ugi-4CR-based macrocyclization emerged from our laboratory 65 in 2001 in the frame of an extended program toward the synthesis of mimics of ansacyclic cyclopeptide alkaloids 66 (cf. 5 in Scheme 3).…”

Section: Chronology Of the Multiple Multicomponent Macrocyclizationsmentioning

confidence: 99%

Multiple Multicomponent Macrocyclizations (MiBs): A Strategic Development Toward Macrocycle Diversity

2009

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Section: Chronology Of the Multiple Multicomponent Macrocyclizationsmentioning

confidence: 99%

Multiple Multicomponent Macrocyclizations (MiBs): A Strategic Development Toward Macrocycle Diversity

2009

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“…[26] In our case, from the different possibilities contemplated to obtain constrained peptidomimetics derived from the identified peptoid hits, those approaches that generated the novel 7-substituted perhydro-1,4-diazepine-2,5-dione 2 and 3-substituted 1,4-piperazine-2,5-dione 3 derivatives were selected (Scheme 1). In these systems, two of the three tertiary amide bonds present in the molecules are forced to adopt the cis configuration by the heterocycle formation.…”

Section: Introductionmentioning

confidence: 99%

Chemical Modulation of Peptoids: Synthesis and Conformational Studies on Partially Constrained Derivatives

Moure

Sanclimens

Bujons

et al. 2011

Chemistry A European J

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The high conformational flexibility of peptoids can generate problems in biomolecular selectivity as a result of undesired off-target interactions. This drawback can be counterbalanced by restricting the original flexibility to a certain extent, thus leading to new peptidomimetics. By starting from the structure of an active peptoid as an apoptosis inhibitor, we designed two families of peptidomimetics that bear either 7-substituted perhydro-1,4-diazepine-2,5-dione 2 or 3-substituted 1,4-piperazine-2,5-dione 3 moieties. We report an efficient, solid-phase-based synthesis for both peptidomimetic families 2 and 3 from a common intermediate. An NMR spectroscopic study of 2a,b and 3a,b showed two species in solution in different solvents that interconvert slowly on the NMR timescale. The cis/trans isomerization around the exocyclic tertiary amide bond is responsible for this conformational behavior. The cis isomers are more favored in nonpolar environments, and this preference is higher for the six-membered-ring derivative 3a,b. We propose that the hydrogen-bonding pattern could play an important role in the cis/trans equilibrium process. These hydrogen bonds were characterized in solution, in the solid state (i.e., by using X-ray studies), and by molecular modeling of simplified systems. A comparative study of a model peptoid 10 containing the isolated tertiary amide bond under study outlined the importance of the heterocyclic moiety for the prevalence of the cis configuration in 2a and 3a. The kinetics of the cis/trans interconversion in 2a, 3a, and 10 was also studied by variable-temperature NMR spectroscopic analysis. The full line-shape analysis of the NMR spectra of 10 revealed negligible entropic contribution to the energetic barrier in this conformational process. A theoretical analysis of 10 supported the results observed by NMR spectroscopic analysis. Overall, these results are relevant for the study of the peptidomimetic/biological-target interactions.

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“…of 0.712(2) and anti with s.o.f. = 0.288 (2). Two positions of the C(20) atom were refined with the same fractional coordinates and anisotropic displacement parameters (constrains were applied with EXYZ and EADP instructions).…”

Section: Methodsmentioning

confidence: 99%

“…Isocyanide-based multi-component reactions (abbreviated to IMCRs by Ugi and Dömling) by virtue of their synthetic potential, inherent atom efficiency, convergent nature, ease of implementation, and the generation of molecular diversity have attracted much attention because of the advantages they offer to the field of combinatorial chemistry [1,2]. Today, IMCR chemistry is mostly related to the classical reactions of Passerini and Ugi [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Single crystal X-ray structure of 2-[({[(4-methylphenyl)sulfonyl]methyl} amino)carbonyl]-1,3-dioxo-2,3-dihydro-1H-inden-2-yl 2-thiophenecarboxylate

et al. 2011

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The title compound 2- [({[(4-methylphenyl)sulfonyl]methyl}amino)carbonyl]-1,3-dioxo-2,3-dihydro-1H-inden-2-yl 2-thiophenecarboxylate is synthesized and studied by the single crystal X-ray diffraction method. The structure of the product is confirmed by IR, 1 H and 13 C NMR spectroscopy, and mass spectrometry. The structure is solved in the C2/c monoclinic space group with a = 16.739 (3) Å, b = 11.087(3) Å, c = 23.194(4) Å, β = 93.32(3)°, V = 4297.2(16) Å 3 , Z = 8, R1 = 0.033 and wR2 = 0.088.

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Design and Synthesis of Cyclic RGD Pentapeptoids by Consecutive Ugi Reactions

Cited by 111 publications

References 29 publications

Multiple Multicomponent Macrocyclizations (MiBs): A Strategic Development Toward Macrocycle Diversity

Multiple Multicomponent Macrocyclizations (MiBs): A Strategic Development Toward Macrocycle Diversity

Chemical Modulation of Peptoids: Synthesis and Conformational Studies on Partially Constrained Derivatives

Single crystal X-ray structure of 2-[({[(4-methylphenyl)sulfonyl]methyl} amino)carbonyl]-1,3-dioxo-2,3-dihydro-1H-inden-2-yl 2-thiophenecarboxylate

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