A convenient transformation of α-alkylserines into α-halogenomethyl-α-alkylglycines

Kudaj, Adam; Olma, Aleksandra

doi:10.1016/j.tetlet.2008.08.098

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…Hydrolysis of benzoylamino‐5‐alkyl‐4‐oxo‐1,3‐dioxanes led to racemic α‐methyl( iso ‐propyl)serine. N ‐Boc‐( R , S )‐α‐alkylserines 1 were synthesized with high yield from the potassium salt of ( R , S )‐α‐alkylserines and Boc 2 O in boiling methanol in the presence of triethylamine as a base and were resolved by fractional crystallization of their diastereoisomeric salt with (‐)‐ephedrine. The specific rotation obtained by N ‐Boc‐amino acids was consistent with that described in the literature .…”

Section: Resultsmentioning

confidence: 99%

The Biological Consequences of Replacing d‐Ala in Biphalin with Amphiphilic α‐Alkylserines

et al. 2014

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Biphalin, a synthetic opioid peptide with a broad affinity for all opioid receptors (δ, μ, and κ) and high antinociceptive activity, has been under extensive study as a potential analgesic drug. This study presents the synthesis and biological properties of four new analogues of biphalin containing amphiphilic α-alkylserines in position 2 and 2'. The incorporation of bulky α,α-disubstituted amino acids in the peptide chain using standard peptide chemistry is often unsuccessful. We synthesized depsipeptides, and then, the desired peptides were obtained by internal O,N-migration of the acyl residue from the hydroxyl to the amino group under mild basic conditions. The potency and selectivity of the new analogues 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). Their binding affinity is strongly dependent on the chirality of α-alkylserine, as analogues containing (R)-α-alkylserines displayed higher μ receptor affinity and selectivity than those incorporating the (S)-isomers.

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Section: Resultsmentioning

confidence: 99%

The Biological Consequences of Replacing d‐Ala in Biphalin with Amphiphilic α‐Alkylserines

et al. 2014

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“…The preparation was carried out under nitrogen atmosphere at -10 .°Cb ya dding 3.3 mmol (0.57 g) diethyl azodicarboxylate (DEAD) to asolution of 3.3 mmol (0.866 g) triphenylphosphine in 6mldry ethyl acetate [1]. After stirring for 15 min the betaine complex [3] was formed (monitored by GC).…”

Section: Source Of Materialsmentioning

confidence: 99%

Crystal structure of N-tosyl-2-methylserine-β-lactone, C11H13NO4S

Lauf¹,

Bruhn²,

Frauenrath³

2010

Zeitschrift Für Kristallographie - New Crystal Structures

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C 11 H 13 NO 4 S, orthorhombic, P2 1 2 1 2 1 (no. 19), a =5.7011(4) Å, b =8.9203(6) Å, c =23.571(2) Å, V =1198.7 Å 3 , Z =4,R gt (F) =0.028, wR ref (F 2 ) =0.062, T =173 K. Source of materialThe preparation was carried out under nitrogen atmosphere at -10 .°Cb ya dding 3.3 mmol (0.57 g) diethyl azodicarboxylate (DEAD) to asolution of 3.3 mmol (0.866 g) triphenylphosphine in 6mldry ethyl acetate [1]. After stirring for 15 min the betaine complex [3] was formed (monitored by GC). Then 3m mol (0.816 .g) N-tosyl-2-methylserine was added, the reaction mixture was stirred for 1hat-10°Cand for further 2hatroom temperature. After dilution with 6m ln -hexane it was stored for 2ha t -20 .°C . The precipitate of N,N'-diethoxycarbonylhydrazine and triphenylphosphine oxide was filtered off. The solvent was removed in vacuo and the oily residue was purified by column chromatography using ethyl acetate/n-hexane (1:1) as eluent (yield 30.-40%). Crystals of the title compound precipitated over aperiod of 3d ays from ah ighly concentrated solution in dichloromethane covered with paraffine oil of low viscosity. Experimental detailsThe absolute configuration was not determind owing to racemic twinning. Hydrogen atoms were added to the model in calculated positions with U iso (H) =1.2 U eq (C) except H1 bound to nitrogen atom which was found in the difference Fourier map and refined without position constraints. This was done because of uncertainty about the hybridization of the Natom, so that position constraints would possibly have led to awrong model. Discussion

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“…N -Boc-α-alkylserines can be easily cyclized under Mitsunobu reaction conditions to Ν -protected β-lactones (Olma and Kudaj 2005 ; Fukujama and Xu 1993 ; Smith and Goodman 2003 ; Olma 2004 ), which are excellent starting materials for further derivatization in medicinal chemistry. We recently reported the synthesis of α-alkyl-β - azido-and α-alkyl-β-aminoalanines as well as α-halogenomethyl-α-alkylglycines (Kudaj and Olma 2007 , 2008 ) via ring opening of 3-amino-3-alkyl-2-oxetanones. Enantiomerically pure N -Boc-α-alkylserines are easily available using a procedure developed in our laboratory, involving the synthesis of racemic α-hydroxymethyl analogues of various amino acids (Kamiński et al 1973 ) and their resolution by fractional crystallization of appropriate diastereoisomeric salts.…”

Section: Introductionmentioning

confidence: 99%

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

2011

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The cyclization of N-Boc-α-alkylserines to corresponding β-lactones under Mitsunobu reaction conditions and the ring opening with heterocyclic amines (pyrrolidine, piperidine, morpholine and thiomorpholine) produced N-Boc-α-alkyl-β-(sec-amino)alanines. The removal of the Boc group gives di-hydrochlorides of non-protein amino acids.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-011-1055-3) contains supplementary material, which is available to authorized users.

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A convenient transformation of α-alkylserines into α-halogenomethyl-α-alkylglycines

Cited by 5 publications

References 25 publications

The Biological Consequences of Replacing d‐Ala in Biphalin with Amphiphilic α‐Alkylserines

The Biological Consequences of Replacing d‐Ala in Biphalin with Amphiphilic α‐Alkylserines

Crystal structure of N-tosyl-2-methylserine-β-lactone, C11H13NO4S

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

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