A convenient route to optically pure α-alkyl-β-(sec-amino)alanines

Olma, Aleksandra; Lasota, Anika; Kudaj, Adam

doi:10.1007/s00726-011-1055-3

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…Fluorenylmethyloxycarbonyl (Fmoc)‐protected amino acids and Fmoc‐Rink amide AM resin were purchased from IrisBiotech (Marktredwitz, Germany). ( R ) and ( S ) N ‐protected α‐methyl‐β‐azido( sec ‐amino)alanines were obtained according to a procedure described in the literature .…”

Section: Methodsmentioning

confidence: 99%

“…N ‐Boc‐α‐alkylserine β‐lactones are useful starting materials for further derivatization yielding potentially interesting building blocks for medicinal chemistry. The treatment of N ‐Boc‐α‐methylserine β‐lactone with free heterocyclic amines (pyrrolidine, piperidine, morpholine or thiomorpholine) gives suitable, enantiomerically pure N ‐protected α‐methyl‐β‐( sec ‐amino)alanines .…”

Section: Introductionmentioning

confidence: 99%

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Analogues of deltorphin I containing conformationally restricted amino acids in position 2: structure and opioid activity

et al. 2014

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New analogues of deltorphin I (DT I, Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2 ), with the D-Ala residue in position 2 replaced by α-methyl-β-azido(amino, 1-pyrrolidinyl, 1-piperidinyl or 4-morpholinyl)alanine, were synthesized by a combination of solid-phase and solution methods. All ten new analogues were tested for receptor affinity and selectivity to μ- and δ-opioid receptors. The affinity of analogues containing (R) or (S)-α-methyl-β-azidoalanine in position 2 to δ-receptors strongly depended on the chirality of the α,α-disubstituted residue. Peptide II, containing (S)-α-methyl-β-azidoalanine in position 2, displayed excellent δ-receptor selectivity with its δ-receptor affinity being only three times lower than that of DT I.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analogues of deltorphin I containing conformationally restricted amino acids in position 2: structure and opioid activity

et al. 2014

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“…An efficient method of synthesizing multifunctional α,α-disubstituted glycines from easily accessible α-alkylserines has been developed by our research team [2]. Racemic N-Boc-α-alkylserine has been resolved by fractional crystallization of diastereoisomeric salts with (-)-ephedrine.…”

Section: Resultsmentioning

confidence: 99%

Structure-Activity Relationships of Constrained Dermorphin Analogues Containing an α-Alkyl-β-Substituted Alanines

Lasota¹,

Frączak²,

Muchowska³

et al. 2015

Peptides 2015, Proceedings of the 24th American Peptide Symposium

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“…Fluorenylmethyloxycarbonyl (Fmoc)‐protected amino acids and Fmoc‐Rink‐Amide AM Resin were purchased from IrisBiotech (Marktredwitz, Germany). ( R ) and ( S ) N ‐Boc‐ α ‐benzyl‐ β ‐azido( sec ‐amino) alanines were obtained according to a procedure described in the literature . All solvents and reagents used for solid‐phase synthesis were of analytical quality and used without further purification.…”

Section: Methodsmentioning

confidence: 99%

“…Optically, pure α , α ‐disubstituted glycines were obtained from available N ‐Boc‐( R or S )‐ α ‐benzylserine β ‐lactone. The treatment of N ‐Boc‐( R or S )‐ α ‐benzylserine β ‐lactone with sodium azide or free heterocyclic amines (pyrrolidine, piperidine, morpholine) as nucleophile gives suitable, enantiomerically pure N ‐Boc‐( R or S )‐ α ‐benzyl‐ β ‐azido( sec ‐amino)alanines .…”

mentioning

confidence: 99%

Synthesis, Biological Activity, and NMR‐Based Structural Studies of Deltorphin I Analogs Modified in Message Domain with a Newα,α‐Disubstituted Glycines

et al. 2016

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This article describes new deltorphin I analogs in which phenylalanine residues were replaced by the corresponding (R) or (S)-α-benzyl-β-azidoalanine, α-benzyl-β-(1-pyrrolidinyl)alanine, α-benzyl-β-(1-piperidinyl)alanine, and α-benzyl-β-(4-morpholinyl)-alanine residues. The potency and selectivity of the new analogs were evaluated by a competitive receptor binding assay in the rat brain using [(3) H]DAMGO (a μ ligand) and [(3) H]DELT (a δ ligand). The affinity of analogs containing (R) or (S)-α-benzyl-β-azidoalanine in position 3 to δ-receptors strongly depended on the chirality of the α,α-disubstituted residue. The conformational behavior of peptides modified with (R) or (S)-α-benzyl-β-(1-piperidinyl)Ala, which displays the opposite selectivity, was analyzed by (1) H and (13) C NMR. The μ-selective Tyr-d-Ala-(R)-α-benzyl-β-(1-piperidinyl)Ala-Asp-Val-Val-Gly-NH2 lacks the helical conformation observed in the δ-selective Tyr-d-Ala-(S)-α-benzyl-β-(1-piperidinyl)Ala-Asp-Val-Val-Gly-NH2 . Our results support the proposal that differences between δ- and μ-selective opioid peptides are attributable to the presence or absence of a spatial overlap between the N-terminal message domain and the C-terminal address domain.

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A convenient route to optically pure α-alkyl-β-(sec-amino)alanines

Cited by 6 publications

References 37 publications

Analogues of deltorphin I containing conformationally restricted amino acids in position 2: structure and opioid activity

Analogues of deltorphin I containing conformationally restricted amino acids in position 2: structure and opioid activity

Structure-Activity Relationships of Constrained Dermorphin Analogues Containing an α-Alkyl-β-Substituted Alanines

Synthesis, Biological Activity, and NMR‐Based Structural Studies of Deltorphin I Analogs Modified in Message Domain with a Newα,α‐Disubstituted Glycines

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