Conformational analysis of (R,S)-4-amido-2,4-dimethyl-butyric acid derivatives

Hoffmann, Reinhard W.; Lázaro, M. A.; Caturla, Francisco; Framery, Éric; Valancogne, Ingrid; Montalbetti, Christian

doi:10.1016/s0040-4039(99)01226-5

Cited by 10 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The trans-arrangement of the substituents in 7 was confirmed by NOE measurements 9. ) Crystallographic data (excluding structure factors; see alsoTable 4 in the Exper.…”

mentioning

confidence: 75%

“…11 ) Hoffmann et al have found for g-amino acid derivatives of type B(Fig. 1)a preference for a gauche conformation of the amido substituent with respect to the main chain[9]. In the turn structure of 1, such a conformation was observed in residue 2 but not in residue 1.…”

mentioning

confidence: 92%

“…This observation was explained by different conformational preferences of the incorporated g-amino acid residues. Hoffmann et al have synthesized a number of 2,4-disubstituted g-amino acid derivatives and investigated their conformations in solution by NMR spectroscopy [9].…”

mentioning

confidence: 99%

“…Dicyclohexylammonium (2S,4R)-2-Benzyl-4-{[(tert-butoxy)carbonyl]amino}pentanoate(9). Compound 5 (1.85 g, 8.0 mmol) was treated with BnBr (4.8 ml, 40 mmol) according to GP 1.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Design, Synthesis, NMR-Solution and X-Ray Crystal Structure ofN-Acyl-γ-dipeptide Amides That Form aβII′-Type Turn

Brenner¹,

Seebàch²

2001

HCA

View full text Add to dashboard Cite

Conformational analysis of g-amino acids with substituents in the 2-position reveals that an N-acyl-gdipeptide amide built of two enantiomeric residues of unlike configuration will form a 14-membered H-bonded ring, i.e., a g-peptidic turn (Figs. 1 ± 3). The diastereoselective preparation of the required building blocks was achieved by alkylation of the doubly lithiated N-Boc-protected 4-aminoalkanoates, which, in turn, are readily available from the corresponding (R)-or (S)-a-amino acids (Scheme 1). Coupling two such g-amino acid derivatives gave N-acetyl and N-[(tert-butoxy)carbonyl] (Boc) dipeptide methyl amides (1 and 10, resp.; Fig. 2, Scheme 2); both formed crystals suitable for X-ray analysis, which confirmed the turn structures in the solid state ( Fig. 4 and Table 4). NMR Analysis of the acetyl derivative 1 in CD 3 OH, with full chemical-shift and coupling assignments, and, including a 300-ms ROESY measurement, revealed that the predicted turn structure is also present in solution ( Fig. 5 and Tables 1 ± 3). The results described here are yet another piece of evidence for the fact that more stable secondary structures are formed with a decreasing number of residues, and with increasing degree of predictability, as we go from a-to b-to g-peptides. Implications of the superimposable geometries of the actual turn segments (with amide bonds flanked by two quasi-equatorial substituents) in a-, b-, and g-peptidic turns are discussed.

show abstract

“…The trans-arrangement of the substituents in 7 was confirmed by NOE measurements 9. ) Crystallographic data (excluding structure factors; see alsoTable 4 in the Exper.…”

mentioning

confidence: 75%

mentioning

confidence: 92%

mentioning

confidence: 99%

“…Dicyclohexylammonium (2S,4R)-2-Benzyl-4-{[(tert-butoxy)carbonyl]amino}pentanoate(9). Compound 5 (1.85 g, 8.0 mmol) was treated with BnBr (4.8 ml, 40 mmol) according to GP 1.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Design, Synthesis, NMR-Solution and X-Ray Crystal Structure ofN-Acyl-γ-dipeptide Amides That Form aβII′-Type Turn

Brenner¹,

Seebàch²

2001

HCA

View full text Add to dashboard Cite

show abstract

“…Solvation of the OH groups could lead to new types of secondary structures, or at least drastically change the properties of the known[7] [11][18] structures 5. ) For conformational analyses of simple l and u 2,4-disubstituted g-amino acid derivatives, see publications by Hoffmann et al[19]. The natural product bleomycin A 2 contains a 4-amino-3-hydroxy-2-methylpentanoic acid moiety[20], and Boger et al[21] have studied the influence of the substitution pattern of this g-amino acid on the DNA-cleaving activity of bleomycin A 2 (cf.…”

mentioning

confidence: 99%

Synthesis and CD Spectra in MeCN, MeOH, and H2O ofγ-Oligopeptides with Hydroxy Groups on the Backbone, Preliminary Communication

Brenner¹,

Seebàch²

2001

HCA

View full text Add to dashboard Cite

Dedicated to Professor Siegfried Hünig with best wishes on the occasion of his 80th birthday g 4 -Tripeptides and g 4 -hexapeptides, 1 ± 4, with OH groups in the 2-or 3-position on each residue have been prepared. The corresponding 2-hydroxy amino acids were obtained by Si-nitronate (3 2) cycloadditions to the acryloyl derivative of Oppolzers sultam and Raney-Ni reduction of the resulting 1,2-oxazolidines (Scheme 1). The 3-hydroxy amino acid derivatives were prepared by chain elongation via Claisen condensation of Boc-Ala-OH, Boc-Val-OH, and Boc-Leu-OH, and NaBH 4 reduction of the methyl 4-amino 3-oxo carboxylates formed (Scheme 2). The N-Boc hydroxy amino acids were coupled in solution to give the g-peptides. CD Spectra of the new types of g-peptides were recorded and compared with those of simple g 2 -, g 3 -, g 4 -, and g 2,3,4 -peptides (Figs. 3, 4, and 5). An intense Cotton effect at ca. 200 nm ([V] À 2´10 5 deg´cm 2´d mol À1 ) indicates that the hexapeptide built of (3R,4S)-4-amino-3-hydroxy acids (with the side chains of Val, Ala, Leu) folds to a secondary structure so far unknown. The stability of peptides from b-and g-amino acids, which carry heteroatoms on their backbones is discussed (Fig.

show abstract

Konformationsdesign offenkettiger Verbindungen

Hoffmann

2000

Angewandte Chemie

View full text Add to dashboard Cite

Am Übergang zum 21. Jahrhundert befasst sich die Chemie zunehmend mit der Funktion, die Molekülen als Wirkstoffen, Rezeptoren oder – im Molekülverband – als Materialien zukommt. Die Tauglichkeit einer Verbindung für eine molekulare Funktion können wir mit den Begriffen der Konstitution und Konfiguration allein nicht ausreichend beschreiben. Eine entscheidende Bedeutung kommt hier zusätzlich der Konformation der Einzelmoleküle als Mittler zwischen molekularer Konstitution und molekularer Funktion zu. Formulierungen wie „Aktivkonformation”︁ oder „kompetente Konformation”︁ lassen dies anklingen. Der Chemiker muss ein Verständnis dafür entwickeln, wie ein flexibles Molekül die für die jeweilige Funktion optimale Konformation (räumliche Gestalt) einnimmt und wie man dies beeinflussen kann. Am Anfang derartiger Überlegungen zu einem Konformationsdesign steht die Frage, wie es denn die Natur im Zuge der Evolution ihrer Funktionsmoleküle erreicht hat, dass flexible Verbindungen die für die jeweilige Funktion optimale Konformation einnehmen. Wir berichten in diesem Aufsatz, wie wir zu einem ansatzweisen Verständnis des „Konformationsdesigns”︁ der Natur im Bereich der Polyketid‐Naturstoffe gelangt sind, wie wir diese Erkenntnisse zu einem Konformationsdesign offenkettiger Moleküle weiterentwickelt haben und welche Anwendungsmöglichkeiten für diese Erkenntnisse sich jetzt schon abzeichnen.

show abstract

Conformational analysis of (R,S)-4-amido-2,4-dimethyl-butyric acid derivatives

Cited by 10 publications

References 28 publications

Design, Synthesis, NMR-Solution and X-Ray Crystal Structure ofN-Acyl-γ-dipeptide Amides That Form aβII′-Type Turn

Design, Synthesis, NMR-Solution and X-Ray Crystal Structure ofN-Acyl-γ-dipeptide Amides That Form aβII′-Type Turn

Synthesis and CD Spectra in MeCN, MeOH, and H2O ofγ-Oligopeptides with Hydroxy Groups on the Backbone, Preliminary Communication

Konformationsdesign offenkettiger Verbindungen

Contact Info

Product

Resources

About