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Asymmetric synthesis of (2S,3S)-3-Me-glutamine and (R)-allo-threonine derivatives proper for solid-phase peptide coupling

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Abstract

Practical new routes for preparation of (2S,3S)-3-Me-glutamine and (R)-allo-threonine derivatives, the key structural components of cytotoxic marine peptides callipeltin O and Q, suitable for the Fmoc-SPPS, were developed. (2S,3S)-Fmoc-3-Me-Gln(Xan)-OH was synthesized via Michael addition reactions of Ni (II) complex of chiral Gly-Schiff base; while Fmoc-(R)-allo-Thr-OH was prepared using chiral Ni (II) complex-assisted α-epimerization methodology, starting form (S)-Thr(tBu)-OH.

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References

  • Aceña JL, Sorochinsky AE, Moriwaki H, Sato T, Soloshonok VA (2013) Synthesis of fluorine-containing α-amino acids in enantiomerically pure form via homologation of Ni(II) complexes of glycine and alanine Schiff bases. J Fluor Chem 155:21–38

    Article  CAS  Google Scholar 

  • Aceña JL, Sorochinsky AE, Soloshonok VA (2014) Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 3: michael addition reactions and miscellaneous transformations. Amino Acids 46:2047–2073

    Article  CAS  PubMed  Google Scholar 

  • Acevedo CM, Kogut EF, Lipton MA (2001) Synthesis and analysis of the sterically constrained l-glutamine and (3S,4R)-3,4-dimethyl-l-pyroglutamic acid. Tetrahedron 57:6353–6359

    Article  CAS  Google Scholar 

  • Cai C, Soloshonok VA, Hruby VJ (2001) Michael addition reaction between chiral Ni(II) complex of glycine and 3-(trans-enoyl)ozazolidin-2-ones. A cases of electron donor-acceptor attractive interaction-controlled face diastereoselectivity. J Org Chem 66:1339–1350

    Article  CAS  PubMed  Google Scholar 

  • Calimsiz S, Lipton MA (2005) Synthesis of N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine: an application of lanthanide-catalyzed transamidation. J Org Chem 70:6218–6221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • D’Auria MV, Zampella A (2002) Stereoselective synthesis of (2R,3R,4R)-3-hydroxy-2,4,6-trimethylheptanoic acid and determination of the absolute stereochemistry of the natural product from callipeltin A. Tetrahedron Asymmetry 13:1237–1239

    Article  Google Scholar 

  • D’Auria MV, Zampella A, Paloma LG, Minale L (1996) Callipeltins B and C; bioactive peptides from a marine Lithistida sponge Callipelta sp. Tetrahedron 52:9589–9596

    Article  Google Scholar 

  • D’Auria MV, Sepe V, D’Orsi R, Bellotta F, Debitus C, Zampella A (2007) Isolation and structural elucidation of callipeltins J-M: antifungal peptides from the marine sponge Latrunculia sp. Tetrahedron 63:131–140

    Article  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 acid. J Org Chem 71:8572–8578

    Article  CAS  PubMed  Google Scholar 

  • Inoue M, Shinohara N, Tanabe S, Takahashi T, Okura K, Itoh H, Mizoguchi Y, Iida M, Lee N, Matsuoka M (2010) Total synthesis of the large non-ribosomal peptide polytheonamide B. Nat Chem 2:280–285

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi M, Konno H (2013) Improved synthesis of d-allothreonine derivatives from l-threonine. Tetrahedron 69:7098–7101

    Article  CAS  Google Scholar 

  • Kikuchi M, Konno H (2014) Total synthesis of callipeltin B and M, peptidyl marine natural products. Org Lett 16:4324–4327

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi M, Nosaka K, Akaji K, Konno H (2011) Solid phase synthesis of callipeltin E isolated from marine sponge Latrunculia sp. Tetrahedron Lett 27:3872–3875

    Article  CAS  Google Scholar 

  • Konno H, Aoyama S, Nosaka K, Akaji K (2007) Stereoselective synthesis of β-methoxytyrosine derivatives for identification of the absolute configuration of callipeltin E. Synthesis 23:3666–3672

    Article  CAS  Google Scholar 

  • Meijere A, Kozhushkov SI, Yufit DS, Grosse C, Kaiser M, Raev VA (2014) (2R,1′S,2′R)- and (2S,1′S,2′R)-3-[2-mono(di, tri)fluoromethylcyclopropyl]- alanines and their incorporation into hormaomycin analogues. Beilstein J Org Chem 10:2844–2857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moriwaki H, Kawashima A, Terada R, Kawamura A, Soloshonok VA (2017) US patent 9, 696, 112, July 4, 2017

  • Nian Y, Wang J, Zhou S, Wang S, Moriwaki H, Kawashima A, Soloshonok VA, Liu H (2015) Recyclable ligands for the non-enzymatic dynamic kinetic resolution of challenging α-amino acids. Angew Chem Int Ed 54:12918–12922

    Article  CAS  Google Scholar 

  • Nian Y, Wang J, Zhou S, Dai W, Wang S, Moriwaki H, Kawashima A, Soloshonok VA, Liu H (2016) Purely chemical approach for preparation of D-amino acids via (S)- to (R)-interconversion of unprotected tailor-made α-amino acids. J Org Chem 81:3501–3508

    Article  CAS  PubMed  Google Scholar 

  • Nian Y, Wang J, Moriwaki H, Soloshonok VA, Liu H (2017) Analysis of crystallographic structures of Ni(II) complexes of α-amino acid Schiff bases: elucidation of the substituent effect on stereochemical preferences. Dalton Trans 46:4191–4198

    Article  CAS  PubMed  Google Scholar 

  • Obkircher M, Stahelin C, Dick F (2008) Formation of Fmoc-β-alanine during Fmoc-protections with Fmoc-OSu. J Pep Sci 14:763–766

    Article  CAS  Google Scholar 

  • Okamoto N, Hara O, Makino K, Hamada Y (2001) Stereoselective synthesis of (3S,4R)-3,4-dimethyl-(S)-glutamine and the absolute stereochemistry of the natural product from papuamides and callipeltin. Tetrahedron Asymmetry 12:1353–1358

    Article  CAS  Google Scholar 

  • Pelay-Gimeno M, Garcia-Ramos Y, Martin MJ, Spengler J, Molina-Guijarro JM, Munt S, Francesch AM, Cuevas C, Tulla-Puche J, Albericio F (2013) The first total synthesis of the cyclodepsipeptide pipecolidepsin A. Nat Commun 4:2352

    Article  PubMed  Google Scholar 

  • Romoff TT, Palmer AB, Mansour N, Creighton CJ, Miwa T, Ejima Y, Moriwaki H, Soloshonok VA (2017) Scale-up synthesis of (R)- and (S)-N-(2-benzoyl-4-chlorophenyl)-1-(3,4-dichlorobenzyl)pyrrolidine-2-carboxamide hydrochloride, a versatile reagent for the preparation of tailor-made α- and β-amino acids in an enantiomerically pure form. Org Process Res Dev 21:732–739

    Article  CAS  Google Scholar 

  • Sepe V, D’Orsi R, Borbone N, D’Auria MV, Bifulco G, Monti MC, Catania A, Zampella A (2006) Callipeltins F–I: new antifungal peptides from the marine sponge Latrunculia sp. Tetrahedron 62:833–840

    Article  CAS  Google Scholar 

  • Soloshonok VA (2002) For a review, see: highly diastereoselective Michael addition reaction between nucleophilic glycine equivalents and β-substituted-α, β-unsaturated carboxylic acid derivatives a general approach to the stereochemically defined and sterically χ-constrained α-amino acids. Curr Org Chem 6:341–364

    Article  CAS  Google Scholar 

  • Soloshonok VA, Kukhar VP, Galushko SV, Svistunova NY, Avilov DV, Kuzmina NA, Raevski NI, Struchkov YT, Pisarevsky AP, Belokon YN (1993) General method for the synthesis of enantiomerically pure β-hydroxy-α-amino acids, containing fluorine atoms in the side chains. Case of stereochemical distinction between methyl and trifluoromethyl groups. X-Ray crystal and molecular structure of the nickel(II) complex of (2S,3S)-2(trifluoromethyl)threonine. J Chem Soc Perkin Trans 1:3143–3155

    Article  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, Belokon YN (1995) Asymmetric aldol reactions of chiral Ni(II)-complex of glycine with aliphatic aldehydes. Stereodivergent synthesis of syn-(2S)- and syn-(2R)-β-alkylserines. Tetrahedron Asymmetry 6:1741–1756

    Article  CAS  Google Scholar 

  • Soloshonok VA, Avilov DV, Kukhar VP (1996a) 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 (1996b) Asymmetric aldol reaction 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, Cai C, Hruby VJ, Meervelt LV, Mischenko N (1999) For definition of “tailor-made amino acids”, see: stereochemically defined C-substituted glutamic acids and their derivatives. 1. An efficient asymmetric synthesis of (2S,3S)-3-trifluoromethylpyroglutamic acids. Tetrahedron 55:12031–12044

    Article  CAS  Google Scholar 

  • Soloshonok VA, Cai C, Hruby VJ (2000a) A practical asymmetric synthesis of enantiomerically pure 3-substituted pyroglutamic acids and related compounds. Angew Chem Int Ed 39:2172–2175

    Article  CAS  Google Scholar 

  • Soloshonok VA, Cai C, Hruby VJ (2000b) Toward design of a practical methodlogy for stereocontrolled synthesis of χ-constrained pyroglutamic acids and related compounds. Virtually complete control of simple diastereoselectivity in the Michael addition reactions of glycine Ni(II) complexes with N-(enol)oxazolidinones. Tetrahedron Lett 41:135–139

    Article  CAS  Google Scholar 

  • Soloshonok VA, Cai C, Hruby VJ (2000c) 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-one. 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, Ellis TK, Yamada T, Ohfune Y (2005) 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 resolving reagents with flexible stereogenic centers. J Am Chem Soc 131:7208–7209

    Article  CAS  PubMed  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 45:691–718

    Article  CAS  PubMed  Google Scholar 

  • Sorochinsky AE, Aceña JL, Moriwaki H, Sato T, Soloshonok VA (2013b) 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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Stierhof M, Hansen KØ, Sharma M, Feussner K, Subko K, Díaz-Rullo FF, Isaksson J, Perez-Victoria I, Clarkeg D, Hansen E, Jaspars M, Tabudravu JN (2016) New cytotoxic callipeltins from the Solomon Island marine sponge Asteropus sp. Tetrahedron 72:6929–6934

    Article  CAS  Google Scholar 

  • Tokairin Y, Konno H (2017) Preparation of (2R,3R,4R)-4-hydroxy-2,4,6-trimethylheptanoic acid via enzymatic desymmetrization. Tetrahedron 73:39–45

    Article  CAS  Google Scholar 

  • Tokairin Y, Maita K, Takeda S, Konno H (2015) Synthesis of orthogonally protected (2R,3R,4S)-4-amino-2,3-di-hydroxyheptane-1,7-dioic acid. Synthesis 47:351–358

    CAS  Google Scholar 

  • Turk JA, Visbal GS, Lipton MA (2003) Asymmetric synthesis of four diastereomers of 3-hydroxy-2,4,6-trimethylheptanoic acid: proof of configuration assignment. J Org Chem 68:7841–7844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshino R, Tokairin Y, Kikuchi M, Konno H (2017a) Synthesis of fully protected (2R,3R,4S)-4-amino-7-guanidino-2,3-dihydroxy heptanoic acid. Tetrahedron Lett 58:1600–1603

    Article  CAS  Google Scholar 

  • Yoshino R, Tokairin Y, Konno H (2017b) Fmoc-OPhth, the reagent of Fmoc protection. Tetrahedron Lett 58:1604–1606

    Article  CAS  Google Scholar 

  • Zampella A, D’Auria MV, Paloma LG, Casapullo A, Minale L, Debitus C, Henin Y (1996) Callipeltin A, an anti-HIV cyclic depsipeptide from the New Caledonian Lithistida sponge Callipelta sp. J Am Chem Soc 118:6202–6209

    Article  CAS  Google Scholar 

  • Zampella A, Randazzo A, Borbone N, Luciani S, Trevisi L, Debitus C, D’Auria MV (2002) Isolation of callipeltins A-C and of two new open-chain derivatives of callipeltin A from the marine sponge Latrunculia sp. A revision of the stereostructure of callipeltins. Tetrahedron Lett 43:6163–6166

    Article  CAS  Google Scholar 

  • Zhou S, Wang J, Chen X, Aceña JL, Soloshonok VA, Liu H (2014) Chemical kinetic resolution of unprotected β-substituted β-amino acids using recyclable chiral ligands. Angew Chem Int Ed 53:7883–7886

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by a Grant-in-Aid from the Japan Society for the Promotion of Science (240145) to H.K. Y.T. is grateful to the Japan Society for the Promotion of Science Fellowships for young scientist (00465). V.A.S. is grateful to IKERBASQUE, the Basque Foundation for Science for financial support.

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Authors and Affiliations

  1. Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata, 992-8510, Japan

    Yoshinori Tokairin & Hiroyuki Konno

  2. Department of Organic Chemistry I, Faculty of Chemistry, University of Basque Country UPV/EHU, Paseo Manuel Lardizabal 3, 20018, San Sebastian, Spain

    Vadim A. Soloshonok

  3. IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza, 48011, Bilbao, Bizkaia, Spain

    Vadim A. Soloshonok

  4. Hamari Chemical Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, 533-0024, Japan

    Hiroki Moriwaki

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  1. Yoshinori Tokairin
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  2. Vadim A. Soloshonok
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  3. Hiroki Moriwaki
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  4. Hiroyuki Konno
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Correspondence to Hiroyuki Konno.

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Tokairin, Y., Soloshonok, V.A., Moriwaki, H. et al. Asymmetric synthesis of (2S,3S)-3-Me-glutamine and (R)-allo-threonine derivatives proper for solid-phase peptide coupling. Amino Acids 51, 419–432 (2019). https://doi.org/10.1007/s00726-018-2677-5

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