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Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: Aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of α-amino acids

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Abstract

This review provides a comprehensive treatment of literature data dealing with asymmetric synthesis of α-amino-β-hydroxy and α,β-diamino acids via homologation of chiral Ni(II) complexes of glycine Schiff bases using aldol and Mannich-type reactions. These reactions proceed with synthetically useful chemical yields and thermodynamically controlled stereoselectivity and allow direct introduction of two stereogenic centers in a single operation with predictable stereochemical outcome. Furthermore, new application of Ni(II) complexes of α-amino acids Schiff bases for deracemization of racemic α-amino acids and (S) to (R) interconversion providing additional synthetic opportunities for preparation of enantiomerically pure α-amino acids, is also reviewed. Origin of observed diastereo-/enantioselectivity in the aldol, Mannich-type and deracemization reactions, generality and limitations of these methodologies are critically discussed.

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References

  • Belokon YN, Bulychev AG, Vitt SV, Struchkov YT, Batsanov AS, Timofeeva TV, Tsyryapkin VA, Ryzhov MC, Lysova LA, Bakhmutov VI, Belikov VM (1985) General method of diastereo- and enantioselective synthesis of β-hydroxy-α-amino acids by condensation of aldehydes and ketones with glycine. J Am Chem Soc 107:4252–4259

    Article  CAS  Google Scholar 

  • Belokon YN, Sagyan AS, Djamgaryan SM, Bakhmutov VI, Belikov VM (1988) Asymmetric synthesis of β-substituted α-amino acids via chiral Ni(II) complex of dehydroalanine. Tetrahedron 44:5507–5514

    Article  CAS  Google Scholar 

  • Belokon YN, Sagyan AS, Djamgaryan SA, Bakhmutov VI, Vitt SV, Batsanov AS, Struchkov YT, Belikov VM (1990) General method for the asymmetric synthesis of anti-diastereoisomers of β-substituted L-2-aminobutanoic acids via chiral nickel(II) Schiff’s base complexes of dehydroaminobutanoic acid. X-Ray crystal and molecular structure of the nickel(II) complex of the Schiff’s base from [(benzylprolyl)amino]benzophenone and dehydroaminobutanoic acid. J Chem Soc Perkin Trans 1, 2301–2310

  • Belokon YN, Tararov VI, Savel’eva TF (1991) Preparative asymmetric synthesis of (R)- and (S)-α-methylserine Ni (II) complex with a Schiff base of α-alanine and (S)-2-[(N-benzylprolyl)amino]benzophenone. Russ Chem Bull 40:1054–1058

    Article  Google Scholar 

  • Belokon YN, Tararov VI, Maleev VI, Savel’eva TF, Ryzhov MG (1998) Improved procedures for the synthesis of (S)-2-[N-(N′-benzylprolyl)amino]-benzophenone (BPB) and Ni(II) complexes of Schiff’s bases derived from BPB and amino acids. Tetrahedron: Asymmetry 9:4249–4252

    Article  CAS  Google Scholar 

  • Belokon YN, Maleev VI, Savel′eva TF, Ikonnikov NS (2001a) Asymmetric synthesis of (S)- and (R)-α-methylserine based on the chiral recyclable reagent (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide. Russ Chem Bull 50:1037–1040

    Article  CAS  Google Scholar 

  • Belokon YN, Kochetkov KA, Ikonnikov NS, Strelkova TV, Harutyunyan SR, Saghiyan AS (2001b) A new synthesis of enantiomerically pure syn-(S)-β-hydroxy-α-amino acids via asymmetric aldol reactions of aldehydes with a homochiral Ni(II)-glycine/(S)-BPB Schiff base complex. Tetrahedron: Asymmetry 12:481–485

    Article  CAS  Google Scholar 

  • Belokon’ YN, Maleev VI, Petrrosyan AA, Savel’eva TF, Ikonnikov NS, Peregudov AS, Khrustalev VN, Saghiyan AS (2002) Halo-substituted (S)-N-(2-benzoylphenyl)-1-benzylpyrolidine-2-carboxamides as new chiral auxiliaries for the asymmetric synthesis of (S)-α-amino acids. Russ Chem Bull 51:1593–1599

    Article  Google Scholar 

  • Bravo P, Farina A, Frigerio M, Meille SV, Viani F, Soloshonok VA (1994) New fluorinated chiral synthons. Tetrahedron: Asymmetry 5:987–1004

    Article  CAS  Google Scholar 

  • Cai C, Yamada T, Tiwari R, Hruby VJ, Soloshonok VA (2004) Application of (S)- and (R)-methyl pyroglutamates as inexpensive, yet highly efficient chiral auxiliaries in the asymmetric Michael addition reactions. Tetrahedron Lett 45:6855–6858

    Article  CAS  Google Scholar 

  • Capone S, Kieltsch I, Flogel O, Lelais G, Togni A, Seebach D (2008) Electrophilic S-trifluoromethylation of cysteine side chains in α- and β-peptides: isolation of trifluoro-methylated Sandostatin ® (octreotide) derivatives. Helv Chim Acta 91:2035–2056

    Article  CAS  Google Scholar 

  • Ellis TK, Hochla VM, Soloshonok VA (2003a) Efficient synthesis of 2-aminoindane-2-carboxylic acid via dialkylation of nucleophilic glycine equivalent. J Org Chem 68:4973–4976

    Article  PubMed  CAS  Google Scholar 

  • Ellis TK, Martin CH, Tsai GM, Ueki H, Soloshonok VA (2003b) Efficient synthesis of sterically constrained symmetrically α,α-disubstituted α-amino acids under operationally convenient conditions. J Org Chem 68:6208–6214

    Article  PubMed  CAS  Google Scholar 

  • Ellis TK, Ueki H, Yamada T, Ohfune Y, Soloshonok VA (2006) Design, synthesis, and evaluation of a new generation of modular nucleophilic glycine equivalents for the efficient synthesis of sterically constrained α-amino acids. J Org Chem 71:8572–8578

    Article  PubMed  CAS  Google Scholar 

  • Kanai M, Yasumoto M, Kuriyama Y, Inomiya K, Katsuhara Y, Higashiyama K, Ishii A (2003) Highly regioselective hydrogenolysis of bis(α-methylbenzyl)amine derivatives affected by the trifluoromethyl substituent on the aromatic ring. Org Lett 5:1007–1010

    Article  PubMed  CAS  Google Scholar 

  • Kieltsch I, Eisenberger P, Togni A (2007) Mild electrophilic trifluoromethylation of carbon- and sulfur-centered nucleophiles by a hypervalent iodine(III)–CF3 reagent. Angew Chem Int Ed 46:754–757

    Article  CAS  Google Scholar 

  • Kieltsch I, Eisenberger P, Stanek K, Togni A (2008) Recent advances in electrophilic CF3-transfer using hypervalent iodine(III) reagents. Chimia 62:260–263

    Article  CAS  Google Scholar 

  • Qin W, Cao F, Li Z, Zhou H, Wan H, Wei P, Shi Y, Ouyang P (2006) Synthesis and crystal structures of complexes of Ni (II) to chiral Schiff bases of (R)- and (S)-serine with (S)- and (R)-2-N-(N′-benzylprolyl)-aminobenzophenone. J Chem Crystallogr 36:61–65

    Article  CAS  Google Scholar 

  • Qiu W, Soloshonok VA, Cai C, Tang X, Hruby VJ (2000) Convenient, large-scale asymmetric synthesis of enantiomerically pure trans-cinnamylglycine and -α-alanine. Tetrahedron 56:2577–2582

    Article  CAS  Google Scholar 

  • Saghiyan AS, Dadayan SA, Petrosyan SG, Manasyan LL, Geolchanyan AV, Djamgaryan SM, Andreasyan SA, Maleev VI, Khrustalev VN (2006a) New chiral NiII complexes of Schiff’s bases of glycine and alanine for efficient asymmetric synthesis of α-amino acids. Tetrahedron: Asymmetry 17:455–467

    Article  CAS  Google Scholar 

  • Saghiyan AS, Manasyan LL, Dadayan SA, Petrosyan SG, Petrosyan AA, Maleev VI, Khrustalev VN (2006b) Novel modified chiral NiII complexes with the Schiff bases of (E)- and (Z)-2-aminobut-2-enoic acids: synthesis and study. Russ Chem Bull 55:442–450

    Article  CAS  Google Scholar 

  • Saghiyan AS, Dadayan AS, Dadayan SA, Mkrtchyan AF, Geolchanyan AV, Manasyan LL, Ajvazyan HR, Khrustalev VN, Hambardzumyan HH, Maleev VI (2010) Rapid asymmetric synthesis of amino acids via NiII complexes based on new fluorine containing chiral auxiliaries. Tetrahedron: Asymmetry 21:2956–2965

    Article  Google Scholar 

  • Soloshonok VA, Hayashi T (1994a) Gold(I)-catalyzed asymmetric aldol reaction of methyl isocyanoacetate with fluorinated benzaldehydes. Tetrahedron Lett 35:2713–2716

    Article  CAS  Google Scholar 

  • Soloshonok VA, Hayashi T (1994b) Gold(I)-catalyzed asymmetric aldol reactions of fluorinated benzaldehydes with an α-isocyanoacetamide. Tetrahedron: Asymmetry 5:1091–1094

    Article  CAS  Google Scholar 

  • Soloshonok VA, Ono T (1996) The effect of substituents on the feasibility of azomethine–azomethine isomerization: new synthetic opportunities for biomimetic transamination. Tetrahedron 52:14701–14712

    Article  CAS  Google Scholar 

  • Soloshonok VA, Kukhar VP, Galushko SV, Rozhenko AB, Kuzmina NA, Kolycheva MT, Belokon YN (1991a) Asymmetric synthesis of organometallic analogs of natural compounds. 5. Method of synthesis of diastereo- and enantiomerically pure fluorine substituted (2S,3R)- and (2R,3R)-β-phenylserines. Izv Akad Nauk SSSR Ser Khim 1906–1913

  • Soloshonok VA, Kukhar VP, Galushko SV, Kolycheva MT, Rozhenko AB, Belokon YN (1991b) Asymmetric synthesis of organoelement analogs of natural products. 3. General method for diastereo- and enantioselective synthesis of fluorine-containing (2R,3S)-β-phenylserines. Izv Akad Nauk SSSR Ser Khim 1166–1175

  • Soloshonok VA, Kukhar VP, Batsanov AS, Galakhov MA, Belokon YN, Struchkov YT (1991c) Asymmetric synthesis of organoelement analogs of natural compounds. 4. Diastereo- and enantioselective synthesis of (2S),(3S)-4,4,4-trifluorothreonine and (2S),(3S)-β-perfluoroalkylserines. Izv Akad Nauk SSSR Ser Khim 1548–1554

  • Soloshonok VA, Svistunova NY, Kukhar′ VP, Kuz′mina NA, Belokon′ YN (1992a) Asymmetric synthesis of organometallic analogs of natural compounds. 8. Reaction of pentafluorobenzaldehyde with the Ni(II) complex of a Schiff base of glycine and (S)-2-[N-(benzylprolyl)amino]benzophenone. Izv Akad Nauk SSSR Ser Khim 687–693

  • Soloshonok VA, Svistunova NY, Kukhar VP, Gudima AO, Kuz′mina NA, Belokon′ YN (1992b) Asymmetric synthesis of organoelement analogs of natural compounds. 6. (2R,3S)-2-Amino-3-hydroxy-5-phosponovaleric acid. Izv Akad Nauk SSSR Ser Khim 1172–1175

  • Soloshonok VA, Kukhar VP, Pustovit Y, Nazaretyan VA (1992c) A new and convenient synthesis of S-trifluoromethyl-containing amino acids. Synlett 657–658

  • Soloshonok VA, Kukhar VP, Galushko SV, Svistunova NY, Avilov DV, Kuzmina NA, Raevski NI, Struchkov YT, Pisarevsky AP, Belokon YN (1993a) General method of diastereo- and enantioselective synthesis of β-hydroxy-α-amino acids by condensation of aldehydes and ketones with glycine. J Chem Soc Perkin Trans 1, 3143–3155

  • Soloshonok VA, Kirilenko AG, Kukhar VP, Resnati G (1993b) Transamination of fluorinated β-keto carboxylic esters. A biomimetic approach to β-polyfluoroalkyl-β-amino acids. Tetrahedron Lett 34:3621–3624

    Article  CAS  Google Scholar 

  • Soloshonok VA, Hayashi T, Ishikawa K, Nagashima N (1994a) Highly diastereoselective aldol reaction of fluoroalkyl aryl ketones with methyl isocyanoacetate catalyzed by silver(I)/triethylamine. Tetrahedron Lett 35:1055–1058

    Article  CAS  Google Scholar 

  • Soloshonok VA, Kirilenko AG, Galushko SV, Kukhar VP (1994b) Catalytic asymmetric synthesis of β-fluoroalkyl β-amino acids via biomimetic [1,3]-proton shift reaction. Tetrahedron Lett 35:5063–5064

    Article  CAS  Google Scholar 

  • Soloshonok VA, Svistunova NY, Skryma RN, Rybalchenko VV, Kukhar VP, Luik AI, Belokon′ YN, Kuz′mina NA (1994c) Asymmetric synthesis of organoelement analogs of natural product. 16. Asymmetric synthesis and investigation into specific bioactivity of (2R,3S)- and (2S,3R)-2-amino-3-hydroxy-4-phosponobutyric acids. Khim Pharm Zh 27:35–37

    Google Scholar 

  • Soloshonok VA, Avilov DV, Kukhar VP, Tararov VI, Saveleva TF, Churkina TD, Ikonnikov NS, Kochetkov KA, Orlova SA, Pysarevsky AP, Struchkov YT, Raevsky NI, Raevsky NI, Belokon YN (1995) Asymmetric aldol reactions of chiral Ni(II)-complex of glycine with aldehydes. Stereodivergent synthesis of syn-(2S)- and syn-(2R)-β-alkylserines. Tetrahedron: Asymmetry 6:1741–1756

    Article  CAS  Google Scholar 

  • Soloshonok VA, Kacharov AD, Hayashi T (1996a) Gold(I)-catalyzed asymmetric aldol reactions of isocyanoacetic acid derivatives with fluoroaryl aldehydes. Tetrahedron 52:245–254

    Article  CAS  Google Scholar 

  • Soloshonok VA, Avilov DV, Kukhar VP (1996b) Asymmetric aldol reactions of trifluoromethyl ketones with a chiral Ni(II) complex of glycine: stereocontrolling effect of the trifluoromethyl group. Tetrahedron 52:12433–12442

    Article  CAS  Google Scholar 

  • Soloshonok VA, Avilov DV, Kukhar VP (1996c) Highly diastereoselective asymmetric aldol reactions of chiral Ni(II) complex of glycine with alkyl trifluoromethyl ketones. Tetrahedron: Asymmetry 7:1547–1550

    Article  CAS  Google Scholar 

  • Soloshonok VA, Avilov DV, Kukhar’ VP, Van Meervelt L, Mischenko N (1997) Highly diastereoselective aza-aldol reactions of a chiral Ni(II) complex of glycine with imines. An efficient asymmetric approach to 3-perfluoroalkyl-2,3-diamino acids. Tetrahedron Lett 38:4671–4674

    Article  CAS  Google Scholar 

  • Soloshonok VA, Cai C, Hruby VJ (1999) Asymmetric Michael addition reactions of chiral Ni(II)-complex of glycine with (N-trans-enoyl)oxazolidines: improved reactivity and stereochemical outcome. Tetrahedron: Asymmetry 10:4265–4269

    Article  CAS  Google Scholar 

  • Soloshonok VA, Cai C, Hruby VJ (2000) A unique case of face diastereoselectivity in the Michael addition reactions between Ni(II)-complexes of glycine and chiral 3-(E-enoyl)-1,3-oxazolidin-2-ones. Tetrahedron Lett 41:9645–9649

    Article  CAS  Google Scholar 

  • Soloshonok VA, Tang X, Hruby VJ (2001) Large-scale asymmetric synthesis of novel sterically constrained 2′,6′-dimethyl- and α,2′,6′-trimethyltyrosine and -phenylalanine derivatives via alkylation of chiral equivalents of nucleophilic glycine and alanine. Tetrahedron 57:6375–6382

    Article  CAS  Google Scholar 

  • Soloshonok VA, Ueki H, Tiwari R, Cai C, Hruby VJ (2004) Virtually complete control of simple and face diastereoselectivity in the Michael addition reactions between achiral equivalents of a nucleophilic glycine and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones: practical method for preparation of β-substituted pyroglutamic acids and prolines. J Org Chem 69:4984–4990

    Article  PubMed  CAS  Google Scholar 

  • Soloshonok VA, Ueki H, Ellis TK (2005a) New generation of nucleophilic glycine equivalents. Tetrahedron Lett 46:941–944

    Article  Google Scholar 

  • Soloshonok VA, Ueki H, Ellis TK, Yamada T, Ohfune Y (2005b) Application of modular nucleophilic glycine equivalents for truly practical asymmetric synthesis of β-substituted pyroglutamic acids. Tetrahedron Lett 46:1107–1110

    Article  CAS  Google Scholar 

  • Soloshonok VA, Ellis TK, Ueki H, Ono T (2009) Resolution/deracemization of chiral α-amino acids using resolving reagents with flexible stereogenic centers. J Am Chem Soc 131:7208–7209

    Article  PubMed  CAS  Google Scholar 

  • Song G, Jin M, Li Z, Ouyang P (2011) Asymmetric synthesis of α, β-diamino acid derivates via Mannich-type reactions of a chiral Ni(II) complex of glycine with N-tosyl imines. Org Biomol Chem 9:7144–7150

    Article  PubMed  CAS  Google Scholar 

  • Sorochinsky AE, Aceña JL, Moriwaki H, Sato T, Soloshonok VA (2013a) Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; Part 1: alkyl halide alkylations. Amino Acids in press. doi:10.1007/s00726-013-1539-4)

  • Sorochinsky AE, Ueki H, Aceña JL, Ellis TK, Moriwaki H, Sato T, Soloshonok VA (2013b) Chemical deracemization and (S) to (R) interconversion of some fluorine-containing α-amino acids. J Fluorine Chem 152:114–118

    Article  CAS  Google Scholar 

  • Sorochinsky AE, Ueki H, Aceña JL, Ellis TK, Moriwaki H, Sato T, Soloshonok VA (2013c) Chemical approach for interconversion of (S)- and (R)-α-amino acids. Org Biomol Chem 11:4503–4507

    Article  PubMed  CAS  Google Scholar 

  • Tang X, Soloshonok VA, Hruby VJ (2000) Convenient, asymmetric synthesis of enantiomerically pure 2′,6′-dimethyltyrosine (DMT) via alkylation of chiral equivalent of nucleophilic glycine. Tetrahedron: Asymmetry 11:2917–2925

    Article  CAS  Google Scholar 

  • Taylor SM, Yamada T, Ueki H, Soloshonok VA (2004) Asymmetric synthesis of enantiomerically pure 4-aminoglutamic acids via methylenedimerization of chiral glycine equivalents with dichloromethane under operationally convenient conditions. Tetrahedron Lett 45:9159–9162

    Article  CAS  Google Scholar 

  • Tsushima T, Kawada K, Ishihara S, Uchida N, Shiratori O, Higaki J, Hirata M (1988) Fluorine containing amino acids and their derivatives. 7. Synthesis and antitumor activity of α- and γ-substituted methotrexate analogs. Tetrahedron 44:5375–5387

    Article  CAS  Google Scholar 

  • Ueki H, Ellis TK, Martin CH, Boettiger TU, Bolene SB, Soloshonok VA (2003) Improved synthesis of proline-derived Ni(II) complexes of glycine: versatile chiral equivalents of nucleophilic glycine for general asymmetric synthesis of α-amino acids. J Org Chem 68:7104–7107

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Shi T, Deng G, Jiang H, Liu H (2008) Highly enantio- and diastereoselective Mannich reactions of chiral Ni(II) glycinates with amino sulfones. Efficient asymmetric synthesis of aromatic α,β-diamino acids. J Org Chem 73:8563–8570

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Lin D, Shi J, Ding X, Zhang L, Jiang H, Liu H (2010) Highly enantio- and diastereoselective Mannich reaction of a chiral nickel(II) glycinate with an α-imino ester for asymmetric synthesis of a 3-aminoaspartate. Synthesis 1205–1208

  • Wang J, Lin D, Zhou S, Ding X, Soloshonok VA, Liu H (2011) Asymmetric synthesis of sterically and electronically demanding linear ω-trifluoromethyl containing amino acids via alkylation of chiral equivalents of nucleophilic glycine and alanine. J Org Chem 76:684–687

    Article  PubMed  CAS  Google Scholar 

  • Yamada T, Okada T, Sakaguchi K, Ohfune Y, Ueki H, Soloshonok VA (2006) Efficient asymmetric synthesis of novel 4-substituted and configurationally stable analogues of thalidomide. Org Lett 8:5625–5628

    Article  PubMed  CAS  Google Scholar 

  • Yamada T, Sakaguchi K, Shinada T, Ohfune Y, Soloshonok VA (2008) Efficient asymmetric synthesis of the functionalized pyroglutamate core unit common to oxazolomycin and neooxazolomycin using Michael reaction of nucleophilic glycine Schiff base with α,β-disubstituted acrylate. Tetrahedron: Asymmetry 19:2789–2795

    Article  CAS  Google Scholar 

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Acknowledgments

We thank IKERBASQUE, Basque Foundation for Science; the Basque Government (SAIOTEK S-PE12UN044) and Hamari Chemicals (Osaka, Japan) for generous financial support.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, 20018, San Sebastián, Spain

    Alexander E. Sorochinsky, José Luis Aceña & Vadim Soloshonok

  2. IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

    Alexander E. Sorochinsky & Vadim Soloshonok

  3. Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska 1, Kiev, 02660, Ukraine

    Alexander E. Sorochinsky

  4. Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, 533, Japan

    Hiroki Moriwaki & Tatsunori Sato

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  1. Alexander E. Sorochinsky
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  2. José Luis Aceña
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  3. Hiroki Moriwaki
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  4. Tatsunori Sato
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  5. Vadim Soloshonok
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Correspondence to Alexander E. Sorochinsky or Vadim Soloshonok.

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Sorochinsky, A.E., Aceña, J.L., Moriwaki, H. et al. Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: Aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of α-amino acids. Amino Acids 45, 1017–1033 (2013). https://doi.org/10.1007/s00726-013-1580-3

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