Convenient, asymmetric synthesis of enantiomerically pure 2′,6′-dimethyltyrosine (DMT) via alkylation of chiral equivalent of nucleophilic glycine

Tang, Xuejun; Soloshonok, Vadim A.; Hruby, Victor J.

doi:10.1016/s0957-4166(00)00250-0

Cited by 82 publications

(31 citation statements)

References 25 publications

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“…[7][8][9][10][11][12][13][14][15][16][17][18] For quite some time, our groups were interested in pursuing new synthetic approaches for preparation of sterically constrained, 19,20 phosphorus, 21,22 and fluorine-containing [23][24][25] AAs. 28,29 Along with other research groups, [30][31][32][33][34][35][36][37][38][39] we showed that chiral nucleophilic glycine equivalents 1 can be transformed to various AAs 2 via general reactions types, such as alkyl halide alkylations, 40,41 Michael, 42,43 aldol, 44,45 and Mannich 46,47 addition reactions. 28,29 Along with other research groups, [30][31][32][33][34][35][36][37][38][39] we showed that chiral nucleophilic glycine equivalents 1 can be transformed to various AAs 2 via general reactions types, such as alkyl halide alkylations, 40,<...>…”

Section: Introductionsupporting

confidence: 58%

Axially chiral Ni(II) complexes of α‐amino acids: Separation of enantiomers and kinetics of racemization

et al. 2018

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Herein we present design, synthesis, chiral HPLC resolution, and kinetics of racemization of axially chiral Ni(II) complexes of glycine and di-(benzyl)glycine Schiff bases. We found that while the ortho-fluoro derivatives are configurationally unstable, the pure enantiomers of corresponding axially chiral ortho-chloro-containing complexes can be isolated by preparative HPLC and show exceptional configurational stability (t from 4 to 216 centuries) at ambient conditions. Synthetic implications of this discovery for the development of new generation of axially chiral auxiliaries, useful for general asymmetric synthesis of α-amino acids, are discussed.

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Section: Introductionsupporting

confidence: 58%

Axially chiral Ni(II) complexes of α‐amino acids: Separation of enantiomers and kinetics of racemization

et al. 2018

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“…These peptidomimetics are prepared by partial modification of amino acid structure, such as N‐methylation, enantioinversion, homologation, β‐amino acids and quaternary amino acids, or by modification in the amide bond, such as urea derivatives and reduced peptide bonds . The other approach employs the incorporation of non‐proteinogenic (synthetic) amino acids in place of native amino acids …”

Section: Figurementioning

confidence: 99%

“…[4] Theo ther approach employs the incorporationo fn on-proteinogenic (synthetic) amino acids in place of native amino acids. [5] Peptide backbone modification resultsi nu nique structural and biological properties. Replacement of a-CH of the amino acid with nitrogen resulted in an ew class of backbone-modified peptidesc ommonly referreda sa zapeptides.…”

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confidence: 99%

AzaGly‐Appended Peptidomimetics Structurally Related to PTR6154 as Potential PKB/Akt Inhibitors

et al. 2017

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We report the synthesis and biological and physiochemical properties of a series of azaGly-appended peptidomimetics. We have developed a simple and facile synthesis for azapeptides on solid support without any side reaction. The azaGly is inserted by in situ reaction of disuccinimidyl carbonate with free amine followed by treatment of hydrazine hydrate at room temperature. The new series of peptidomimetics was prepared by azaGly scanning of heptapeptide Arg-Pro-Arg-Nle-Tyr-Dap-Nle (Akt-01), a GSK-3β-derived Akt inhibitor. The azaGly-appended peptides showed significant improvement in biological activity and serum stability, with retention of conformation as evidenced by NMR and CD studies. The results clearly demonstrate that azaGly-appended peptides are new peptidomimetics. Their synthesis makes this approach highly useful for the development of novel peptidomimetics of therapeutic potential.

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“…One of these approaches is the introduction of modified amino acids with dimethyltyrosine in strategic positions of peptides to reduce the number of side-chain conformers, thus increasing the peptide biological activity. A successful example of this approach is the recent report of high affinity and ultra selective d-opioid dipeptide antagonist (Schiller et al 1993;Balboni et al 1997;Salvadori et al 1997;Schiller et al 1999;Qiu et al 2001;Soloshonok et al 2001a, b;Tang et al 2000). Our approach does not involve modifications of amino acids, but strategic substitutions of amino acids in the peptide sequence to restrict the number of possible structures that peptide can acquire in solution.…”

Section: Introductionmentioning

confidence: 91%

Decreasing the configurational entropy and the hydrophobicity of EBV-derived peptide 11389 increased its antigenicity, immunogenicity and its ability of inducing IL-6

et al. 2011

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Peptide 11389 from CD21-binding region of EBV-gp350/220 protein binds to PBMCs inducing IL-6 expression and inhibiting EBV-binding to PBMCs. In addition, anti-peptide 11389 antibodies recognize EBV-infected cells and inhibit both EBV infection and IL-6 production in PBMCs. We have postulated that native structure stabilization of peptide 11389 sequence can increase its biological activity. The strategy was to modify its sequence to restrict the number of structures that peptide 11389 could acquire in solution (decreasing peptide's configurational entropy) and to weaken the non-relevant intermolecular interactions (decreasing its hydrophobicity), preserving CD21-interacting residues and structure as displayed in the native protein. Thirteen analog peptides were designed and synthesized; most of them were monomers containing an intra-chain disulfide bridge. Analog peptides 34058, 34060, 34061, 34296, 34298, 34299 and 34300 inhibited EBV invasion of PBMCs. Peptides 34059, 34060, 34295 and 34297 induced IL-6 levels in PBMCs (EC50=3.4, 3.3, 0.5, 0.5 μM, respectively) at higher potency than peptide 11389 (EC50=5.8 μM). Peptides 34057, 34059, 34060, 34301 and 34302 interacted with anti-EBV antibodies with affinities from 3 to 50 times higher than peptide 11389. Most of analog peptides were highly immunogenic and elicited antibodies that cross-react with EBV. In conclusion, we have designed peptides displaying higher biological activity than peptide 11389.

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Convenient, asymmetric synthesis of enantiomerically pure 2′,6′-dimethyltyrosine (DMT) via alkylation of chiral equivalent of nucleophilic glycine

Cited by 82 publications

References 25 publications

Axially chiral Ni(II) complexes of α‐amino acids: Separation of enantiomers and kinetics of racemization

Axially chiral Ni(II) complexes of α‐amino acids: Separation of enantiomers and kinetics of racemization

AzaGly‐Appended Peptidomimetics Structurally Related to PTR6154 as Potential PKB/Akt Inhibitors

Decreasing the configurational entropy and the hydrophobicity of EBV-derived peptide 11389 increased its antigenicity, immunogenicity and its ability of inducing IL-6

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