An efficient synthesis of dehydroamino acids and dehydropeptides from O-Cbz and O-Eoc derivatives of serine and threonine

Ramesh, Ramapanicker; De, Kavita; Chandrasekaran, Srinivasan

doi:10.1016/j.tet.2007.07.094

Cited by 24 publications

(21 citation statements)

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“…and 2e45 was described elsewhere. Synthesis of Boc-L-Val-Z-∆Phe-OMe (2c): Compound 1c (1.97 g, 5 mmol) was treated according to the procedure described above to give compound 2c (1.70, 90 %) as a white solid; mp 152.0-153.0 ºC; 1 H NMR (300 MHz, CDCl 3 , δ): 1.00 (dd, J = 6 6.…”

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confidence: 99%

New self-assembled supramolecular hydrogels based on dehydropeptides

et al. 2015

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Supramolecular hydrogels rely on small molecules that self-assemble in water as a result of the cooperative effect of several relatively weak intermolecular interactions. Peptide-based low molecular weight hydrogelators have attracted enormous interest owing to the simplicity of small molecules combined with the versatility and biocompatibility of peptides. In this work, naproxen, a well known non-steroidal anti-inflammatory drug, was N-conjugated with various dehydrodipeptides to give aromatic peptide amphiphiles that resist proteolysis. Molecular dynamic simulations were used to obtain insight into the underlying molecular mechanism of self-assembly and to rationalize the design of this type of hydrogelators. The results obtained were in excellent agreement with the experimental observations. Only dehydrodipeptides having at least one aromatic amino acid gave hydrogels. The characterization of the hydrogels was carried out using transmission electron microscopy (TEM), circular dichroism (CD), fluorescence spectroscopy and also rheological assays. Results and discussion SynthesisFive new dehydrodipeptides N-protected with naproxen (Npx) were prepared from the corresponding methyl esters of N-tertbutoxycarbonyl-β-hydroxydipeptides. The strategy deployed involved a dehydration reaction followed by cleavage of the tert-butoxycarbonyl group (Boc), reaction with (S)-(+)naproxen chloride and alkaline hydrolysis of the methyl esters (Scheme 1). The dehydroamino acids used were dehydrophenylalanine (∆Phe) and dehydroaminobutyric acid (∆Abu). This synthetic methodology was chosen to avoid racemization issues concerning the naproxen moiety. The N,Cdiprotected dipeptides having a β-hydroxyamino acid (Scheme 1, 1a-e) were dehydrated in good to high yields by treatment with tert-butyldicarbonate (Boc 2 O) and 4dimethylaminopyridine (DMAP) followed by N,N,N',N'tetramethylguanidine (TMG) 17 (Scheme 1, 2a-e). The Boc group was removed with trifluoroacetic acid (TFA) (Scheme 1, 3a-e) and the N-deprotected dehydrodipeptides were conjugated with (S)-(+)-naproxen (Scheme 1, 4a-e). Finally, the methyl esters were removed by treatment with a solution of NaOH (1 M) affording compounds 5a-e in good yields (Scheme 1).

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New self-assembled supramolecular hydrogels based on dehydropeptides

et al. 2015

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“…However, the Poc derivatives of serine and threonine were not stable to treatment with DBU in DMF, which resulted in the formation of corresponding dehydroamino acid derivatives. 8 The elimination of Poc group was observed only when the reaction was performed in DMF as the solvent. 8 We were interested in examining the possibilities of using the O-Poc derivatives (4a-i) in solution phase peptide synthesis.…”

Section: Resultsmentioning

confidence: 99%

“…8 The elimination of Poc group was observed only when the reaction was performed in DMF as the solvent. 8 We were interested in examining the possibilities of using the O-Poc derivatives (4a-i) in solution phase peptide synthesis. Since the Boc group can easily be deprotected with 50% TFA in CH 2 Cl 2 , 3 the Poc derivatives 4a, 4b, 4e, 4f and 4h could be used for solution phase peptide synthesis after removal of the Boc group.…”

Section: Resultsmentioning

confidence: 99%

“…Efforts to hydrolyse the ester groups in 4a-i resulted in the deblocking of the Poc group or in the formation of dehydroamino acids. 8 We overcame this problem by preparing the Poc derivative, BocThr-(Poc)-OPfp (9) from the pentafluorophenyl ester Boc-Thr-OPfp (8) using 2 (scheme 3). Treating the active ester 9 with H-Pro-OMe (10) We anticipated that the deprotection of the O-Poc groups from the dipeptides (7a-i) could be achieved by treating them with tetrathiomolybdate (1).…”

Section: Resultsmentioning

confidence: 99%

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Propargyloxycarbonyl as a protecting group for the side chains of serine, threonine and tyrosine

Ramesh

Gupta

et al. 2008

J Chem Sci

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Propargyloxycarbonyl group is used as a protecting group for the hydroxyl groups of serine, threonine and tyrosine. The propargyloxycarbonyl derivatives of these hydroxy amino acids are stable to acidic and basic reagents commonly employed in peptide synthesis. The deprotection of the O-Poc derivatives using tetrathiomolybdate does not affect commonly used protecting groups such as N-Boc, NCbz, N-Fmoc, methyl and benzyl esters. The di-and tripeptides synthesized using O-Poc derivatives of serine, threonine and tyrosine are stable, isolable compounds and give the hydroxy peptides in good yields when treated with tetrathiomolybdate.

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“…Ferreira et al [14a] have reported a mild and high yielding procedure for the direct elimination of serine and threonine derivatives using Boc 2 O and 4-dimethylaminopyridine to corresponding dehydroamino acid derivatives. Recently, an antiselective β-elimination of serine and threonine to the corresponding α, β-dehydroamino acids has been reported using K 2 CO 3 in dimethylformamide (DMF) [18]. More recently, a nucleophilic addition to nitroacrylates has been applied to the synthesis of 2,3dehydroamino acids [19].…”

Section: Introductionmentioning

confidence: 99%

Stereoselective synthesis of functional dehydrophenylalanine derivatives from novel β‐chloroamino esters

Elemine¹,

Ennigrou²,

Besbes³

2011

Heteroatom Chemistry

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New functional dehydrophenylalanines 3 were prepared from β-amino alcohols 1 in a twostep reaction sequence. The synthesis involved chlorination of the starting amino alcohols 1 to afford the intermediate erythro β-chloroamines 2. Treatment of the latter with an appropriate base led to a highly stereoselective elimination reaction, giving the corresponding (E)-dehydrophenylalanine derivatives 3 in high yields. C 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:91-98, 2012; View this article online at wileyonlinelibrary.com.

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An efficient synthesis of dehydroamino acids and dehydropeptides from O-Cbz and O-Eoc derivatives of serine and threonine

Cited by 24 publications

References 10 publications

New self-assembled supramolecular hydrogels based on dehydropeptides

New self-assembled supramolecular hydrogels based on dehydropeptides

Propargyloxycarbonyl as a protecting group for the side chains of serine, threonine and tyrosine

Stereoselective synthesis of functional dehydrophenylalanine derivatives from novel β‐chloroamino esters

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