Skip to main content
SpringerLink
Log in

Synthesis of Constrained Peptidomimetics via the Pictet-Spengler Reaction

  • Chapter
  • First Online:
Peptidomimetics II

Part of the book series: Topics in Heterocyclic Chemistry ((TOPICS,volume 49))

  • 874 Accesses

Abstract

Peptidomimetics offers a solution to the poor pharmacokinetic properties displayed by natural peptides, by providing pharmaceutically useful chemical structures with the ability to mimic the endogenous polyamide structure. This chapter gives an overview of the past decade’s developments in the field of Pictet-Spengler reactions for the synthesis of peptidomimetics, with an emphasis on the applications of constrained heterocycles in mimicry of peptide geometry and biology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389:251–260

    Article  CAS  Google Scholar 

  2. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    Article  CAS  Google Scholar 

  3. Hurwitz J (2005) The discovery of RNA polymerase. J Biol Chem 280:42477–42485

    Article  CAS  Google Scholar 

  4. Furie B, Furie BC (1988) The molecular basis of blood coagulation. Cell 53:505–518

    Article  CAS  Google Scholar 

  5. Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S (2002) Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett 520:97–101

    Article  CAS  Google Scholar 

  6. Doyle DA, Cabral JM, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1988) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:69–77

    Article  Google Scholar 

  7. Adessi C, Soto C (2002) Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr Med Chem 9:963–978

    Article  CAS  Google Scholar 

  8. Chatterjee S, Roy RS, Balaram P (2007) Expanding the polypeptide backbone: hydrogen-bonded conformations in hybrid polypeptides containing the higher homologues of α-amino acids. J R Soc Interface 4:587–606

    Article  CAS  Google Scholar 

  9. Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577–2637

    Article  CAS  Google Scholar 

  10. Liskamp RMJ (1994) Conformationally restricted amino acids and dipeptides, (non)peptidomimetics and secondary structure mimetics. Recl Trav Chim Pays-Bas 113:1–19

    Article  CAS  Google Scholar 

  11. Powell MF, Grey H, Gaeta F, Sette A, Colón S (1992) Peptide stability in drug development: a comparison of peptide reactivity in different biological media. J Pharm Sci 81:731–735

    Article  CAS  Google Scholar 

  12. Bursavich MG, Rich DH (2002) Designing non-peptide peptidomimetics in the 21st century: inhibitors targeting conformational ensembles. J Med Chem 45:541–558

    Article  CAS  Google Scholar 

  13. Olson GL, Bolin DR, Bonner MP, Bös M, Cook CM, Fry DC, Graves BJ, Hatada M, Hill DE, Kahn M, Madison VS, Rusiecki VK, Sarabu R, Sepinwall J, Vincent GP, Voss ME (1993) Concepts and progress in the development of peptide mimetics. J Med Chem 36:3039–3049

    Article  CAS  Google Scholar 

  14. Gante J (1994) Peptidomimetics – tailored enzyme inhibitors. Angew Chem Int Ed 33:1699–1720

    Article  Google Scholar 

  15. Ripka AS, Rich DH (1998) Peptidomimetic design. Curr Opin Chem Biol 2:441–452

    Article  CAS  Google Scholar 

  16. Marshall GR (1993) A hierarchical approach to peptidomimetic design. Tetrahedron 49:3547–3558

    Article  CAS  Google Scholar 

  17. Giannis A, Kolter T (1993) Peptidomimetics for receptor ligands – discovery, development, and medical perspectives. Angew Chem Int Ed 32:1244–1267

    Article  Google Scholar 

  18. Hruby V (1982) Conformational restrictions of biologically active peptides via amino acid side chain groups. Life Sci 31:189–199

    Article  CAS  Google Scholar 

  19. Toniolo C (1990) Conformationally restricted peptides through short-range cyclizations. Int J Pept Protein Res 35:287–300

    Article  CAS  Google Scholar 

  20. Hruby VJ, Li G, Haskell-Luevano C, Shenderovich M (1997) Design of peptides, proteins and peptidomimetics in chi space. Biopolymers 43:219–266

    Article  CAS  Google Scholar 

  21. Gibson (née Thomas) SE, Guillo N, Tozer MJ (1999) Towards control of χ-space: conformationally constrained analogues of Phe, Tyr, Trp and His. Tetrahedron 55:585–615

    Google Scholar 

  22. Choudhary A, Raines RT (2011) An evaluation of peptide-bond isosteres. ChemBioChem 12:1801–1807

    Article  CAS  Google Scholar 

  23. Seebach D, Beck AK, Bierbaum DJ (2004) The world of β- and γ-peptides comprised of homologated proteinogenic amino acids and other components. Chem Biodiversity 1:1111–1239

    Article  CAS  Google Scholar 

  24. Fowler SA, Blackwell HE (2009) Structure-function relationships in peptoids: recent advances toward deciphering the structural requirements for biological function. Org Biomol Chem 7:1508–1524

    Article  CAS  Google Scholar 

  25. Chorev M, Goodman M (1993) A dozen years of retro-inverso peptidomimetics. Acc Chem Res 26:266–273

    Article  CAS  Google Scholar 

  26. Hughes J (1975) Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Res 88:295–308

    Article  CAS  Google Scholar 

  27. Hughes J, Smith T, Morgan B, Fothergill L (1975) Purification and properties of enkephalin – the possible endogenous ligand for the morphine receptor. Life Sci 16:1753–1758

    Article  CAS  Google Scholar 

  28. Tipper DJ, Strominger JL (1965) Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc Natl Acad Sci U S A 54:1133–1141

    Article  CAS  Google Scholar 

  29. Yocum RR, Rasmussen JR, Strominger JL (1980) The mechanism of action of penicillins. J Biol Chem 255:3977–3986

    CAS  Google Scholar 

  30. Swindells DCN, White PS, Findlay JA (1978) The X-ray crystal structure of rapamycin, C51H79NO13. Can J Chem 56:2491–2492

    Article  CAS  Google Scholar 

  31. Choi J, Chen J, Schreiber SL, Clardy J (1996) Structure of the FKB12-rapamycin complex interacting with the binding domain of human FRAP. Science 273:239–242

    Article  CAS  Google Scholar 

  32. Pictet A, Spengler T (1911) Über die bildung von Isochinolin-derivaten durch Einwirkung von Methylal auf Phenyl-äthylamin, Phenyl-alanin und Tyrosin. Chem Ber 44:2030–2036

    Article  CAS  Google Scholar 

  33. Cox ED, Cook JM (1995) The Pictet-Spengler condensation: a new direction for an old reaction. Chem Rev 95:1797–1842

    Article  CAS  Google Scholar 

  34. Tatsui G (1928) J Pharm Soc Jpn 48:453–459

    CAS  Google Scholar 

  35. Bailey PD, Hollinshead SP, McLay NR, Morgan K, Palmer SJ, Prince SN, Reynolds CD, Wood SD (1993) Diastereo- and enantio-selectivity in the Pictet-Spengler reaction. J Chem Soc Perkin Trans 1:431–439

    Google Scholar 

  36. Jacobs WA, Craig LC (1936) The ergot alkaloids* VIII. The synthesis of 4-carboline carbonic acids. J Biol Chem 113:759–765

    CAS  Google Scholar 

  37. Wadsworth A, Pangborn MC (1936) The reaction of formaldehyde with amino acids. J Biol Chem 116:423–436

    CAS  Google Scholar 

  38. Stöckigt J, Zenk MH (1977) Isovincoside (strictosidine), the key intermediate in the enzymatic formation of indole alkaloids. FEBS Lett 79:233–237

    Article  Google Scholar 

  39. Hampp N, Zenk MH (1988) Homogeneous strictosidine synthase from cell suspension cultures of Rauvolfia serpentina. Phytochemistry 27:3811–3815

    Article  CAS  Google Scholar 

  40. Stöckigt J, Zenk MH (1977) Strictosidine (isovincoside): the key intermediate in the biosynthesis of monoterpenoid indole alkaloids. J Chem Soc Chem Commun 646–648

    Google Scholar 

  41. Stöckigt J (1979) Enzymatic formation of intermediates in the biosynthesis of ajmalicine: strictosidine and cathenamine. Phytochemistry 18:965–971

    Article  Google Scholar 

  42. O’Conner SE, Maresh JJ (2006) Chemistry and biology of monoterpene indole alkaloid biosynthesis. Nat Prod Rep 23:532–547

    Article  Google Scholar 

  43. Ma X, Panjikar S, Koepke J, Loris E, Stöckigt J (2006) The structure of Rauvolfia serpentina strictosidine synthase is a novel six-bladed β-propeller fold in plant proteins. Plant Cell 18:907–920

    Article  CAS  Google Scholar 

  44. McCoy E, Galan MC, O’Connor SE (2006) Substrate specificity of strictosidine synthase. Bioorg Med Chem Lett 16:2475–2478

    Article  CAS  Google Scholar 

  45. Rueffer M, El-Shagi H, Nagakura N, Zenk MH (1981) (S)-Norlaudanosoline synthase: the first enzyme in the benzylisoquinoline biosynthetic pathway. FEBS Lett 129:5–9

    Article  CAS  Google Scholar 

  46. Samanani N, Facchini PJ (2002) Purification and characterization of norcoclaurine synthase. J Biol Chem 277:33878–33883

    Article  CAS  Google Scholar 

  47. Stadler R, Kutchan TM, Loeffler S, Nagakura N, Cassels B, Zenk MH (1987) Revision of the early steps of reticuline biosynthesis. Tetrahedron Lett 28:1251–1254

    Article  CAS  Google Scholar 

  48. Stadler R, Zenk MH (1990) A revision of the generally accepted pathway for the biosynthesis of the benzyltetrahydroisoquinoline alkaloid reticuline. Liebigs Ann Chem 555–562

    Google Scholar 

  49. Rueffer M, Zenk MH (1987) Distant precursors of benzylisoquinoline alkaloids and their enzymatic formation. Z Naturforsch 42c:319–332

    Google Scholar 

  50. Facchini PJ, St-Pierre B (2005) Synthesis and trafficking of alkaloid biosynthetic enzymes. Curr Opin Plant Biol 8:657–666

    Article  CAS  Google Scholar 

  51. Luk LYP, Bunn S, Liscombe DK, Facchini PJ, Tanner ME (2007) Mechanistic studies on norcoclaurine synthase of benzylisoquinoline alkaloid biosynthesis: an enzymatic Pictet-Spengler reaction. Biochemistry 46:10153–10161

    Article  CAS  Google Scholar 

  52. Yan W, Ge HM, Wang G, Jiang N, Mei YN, Jiang R, Li SJ, Chen CJ, Jiao RH, Xu Q, Ng SW, Tan RX (2014) Pictet-Spengler reaction-based biosynthetic machinery in fungi. Proc Natl Acad Sci U S A 111:18138–18143

    Article  CAS  Google Scholar 

  53. Stöckigt J, Antonchick AP, Wu F, Waldmann H (2011) The Pictet-Spengler reaction in nature and organic chemistry. Angew Chem Int Ed 50:8538–8564

    Article  Google Scholar 

  54. Royer J, Bonin M, Micouin L (2004) Chiral heterocycles by iminium ion cyclization. Chem Rev 104:2311–2352

    Article  CAS  Google Scholar 

  55. Taylor MS, Jacobsen EN (2004) Highly enantioselective catalytic acyl-Pictet-Spengler reactions. J Am Chem Soc 126:10558–10559

    Article  CAS  Google Scholar 

  56. Mittal N, Sun DX, Seidel D (2014) Conjugate-base-stabilized Brønsted acids: catalytic enantioselective Pictet-Spengler reactions with unmodified tryptamine. Org Lett 16:1012–1015

    Article  CAS  Google Scholar 

  57. Waldmann H, Schmidt G, Henke H, Burkard M (1995) Asymmetric Pictet-Spengler reactions employing N, N-phthaloyl amino acids as chiral auxiliary groups. Angew Chem Int Ed 34:2402–2403

    Article  CAS  Google Scholar 

  58. Schmidt G, Waldmann H, Henke H, Burkard M (1996) Asymmetric control in the Pictet-Spengler reaction by means of N-protected amino acids as chiral auxiliary groups. Chem Eur J 2:1566–1571

    Article  CAS  Google Scholar 

  59. Gremmen C, Wanner MJ, Koomen G-J (2001) Enantiopure tetrahydroisoquinolines via N-sulfinyl Pictet-Spengler reactions. Tetrahedron Lett 42:8885–8888

    Article  CAS  Google Scholar 

  60. Gremmen C, Willemse B, Wanner MJ, Koomen G-J (2000) Enantiopure tetrahydro-β-carbolines via Pictet-Spengler reactions with N-sulfinyl tryptamines. Org Lett 2:1955–1958

    Article  CAS  Google Scholar 

  61. Bailey PD, Beard M, Phillips TR (2009) Unexpected cis selectivity in the Pictet-Spengler reaction. Tetrahedron Lett 50:3645–3647

    Article  CAS  Google Scholar 

  62. Ungemach F, DiPierro M, Weber R, Cook JM (1979) Stereospecific synthesis of trans-1,3-disubstituted-1,2,3,4-tetrahydro-β-carbolines. Tetrahedron Lett 35:3225–3228

    Article  Google Scholar 

  63. Ungemach F, DiPierro M, Weber R, Cook JM (1981) Stereospecific synthesis of trans-1,3-disubstituted-1,2,3,4-tetrahydro-β-carbolines. J Org Chem 46:164–168

    Article  CAS  Google Scholar 

  64. Julian PL, Karpel WJ, Magnani A, Meyer EW (1948) Studies on the indole series. X. Yohimbine (part 2). The synthesis of yobyrine, yobyrone and “tetrahydroyobyrine”. J Am Chem Soc 70:180–183

    Article  CAS  Google Scholar 

  65. Verschueren K, Toth G, Tourwé D, Lebl M, Van Binst G, Hruby V (1992) A facile synthesis of 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid, a conformationally constrained tyrosine analogue. Synthesis 458–460

    Google Scholar 

  66. Harvey DG, Miller EJ, Robson W (1941) The Adamkiewicz, Hopkins and Cole, and Rosenheim tests for tryptophan. An investigation of the configuration of the organic molecule responsible for the colour formation and its bearing on the constitution of yohimbine, with a note on the action of formaldehyde on tryptophan. J Chem Soc 153–159

    Google Scholar 

  67. Neuberger A (1944) The reaction between histidine and formaldehyde. Biochem J 38:309–314

    Article  CAS  Google Scholar 

  68. Kazmierski W, Hruby VJ (1988) A new approach to receptor ligand design: synthesis and conformation of a new class of potent and highly selective μ opioid antagonists utilizing tetrahydroisoquinoline carboxylic acids. Tetrahedron 44:697–710

    Article  CAS  Google Scholar 

  69. Kazmierski W, Wire WS, Lui GK, Knapp RJ, Shook JE, Burks TF, Yamamura HI, Hruby VJ (1988) Design and synthesis of somatostatin analogues with topographical properties that lead to highly potent and specific μ opioid receptor antagonists with greatly reduced binding at somatostatin receptors. J Med Chem 31:2170–2177

    Article  CAS  Google Scholar 

  70. Schiller PW, Nguyen TM-D, Weltrowska G, Wilkes BC, Marsden BJ, Lemieux C, Chung NN (1992) Differential stereochemical requirements of μ vs. δ opioid receptors for ligand binding and signal transduction: development of a class of potent and highly δ-selective peptide antagonists. Proc Natl Acad Sci U S A 89:11871–11875

    Article  CAS  Google Scholar 

  71. Lesma G, Salvadori S, Airaghi F, Murray TF, Recca T, Sacchetti A, Balboni G, Silvani A (2013) Structural and biological exploration of Phe3-Phe4-modified endomorphin-2 peptidomimetics. ACS Med Chem Lett 4:795–799

    Article  CAS  Google Scholar 

  72. Wang H, Ganesan A (1999) The N-acyliminium Pictet-Spengler condensation as a multicomponent combinatorial reaction on solid-phase and its application to the synthesis of demethoxyfumitremorgin C analogues. Org Lett 1:1647–1649

    Article  CAS  Google Scholar 

  73. van Loevezijn A, van Maarseveen JH, Stegman K, Visser GM, Koomen G-J (1998) Solid phase synthesis of fumitremorgin, verruculogen and tryprostatin analogs based on a cyclization/cleavage strategy. Tetrahedron Lett 39:4737–4740

    Article  Google Scholar 

  74. van Loevezijn A, Allen JD, Schinkel AH, Koomen G-J (2001) Inhibition of BCRP-mediated drug efflux by fumitremorgin-type indolyl diketopiperazines. Bioorg Med Chem Lett 11:29–32

    Article  Google Scholar 

  75. Lazarus LH, Bryant SD, Cooper PS, Guerrini R, Balboni G, Salvadori S (1998) Design of δ-opioid peptide antagonists for emerging drug applications. Drug Discov Today 3:284–294

    Article  CAS  Google Scholar 

  76. Lesma G, Meschini E, Recca T, Sacchetti A, Silvani A (2007) Synthesis of tetrahydroisoquinoline-based pseudopeptides and their characterization as suitable reverse turn mimetics. Tetrahedron 63:5567–5578

    Article  CAS  Google Scholar 

  77. Landoni N, Lesma G, Sacchetti A, Silvani A (2007) Pyrroloisoquinoline-based tetrapeptide analogues mimicking reverse-turn secondary structures. J Org Chem 72:9765–9768

    Article  CAS  Google Scholar 

  78. Deaudelin P, Lubell WD (2008) Diastereoselective Pictet-Spengler approach for the synthesis of pyrrolo[3,2-e][1,4]diazepin-2-one peptide turn mimics. Org Lett 10:2841–2844

    Article  CAS  Google Scholar 

  79. Boutard N, Dufour-Gallant J, Deaudelin P, Lubell WD (2011) Pyrrolo[3,2-e][1,4]diazepin-2-one synthesis: a head-to-head comparison of soluble versus insoluble supports. J Org Chem 76:4533–4545

    Article  CAS  Google Scholar 

  80. Stazi F, Marcoux D, Poupon J-C, Latassa D, Charette AB (2007) Tetraarylphosphonium salts as soluble supports for the synthesis of small molecules. Angew Chem Int Ed 46:5011–5014

    Article  CAS  Google Scholar 

  81. Dufour-Gallant J, Chatenet D, Lubell WD (2015) De novo conception of small molecule modulators based on endogenous peptide ligands: pyrrolodiazepin-2-one γ-turn mimics that differentially modulate urotensin II receptor-mediated vasoconstriction ex vivo. J Med Chem 58:4624–4637

    Article  CAS  Google Scholar 

  82. Hanyu M, Takada Y, Hashimoto H, Kawamura K, Zhang M-R, Fukumura T (2013) Carbon-11 radiolabeling of an oligopeptide containing tryptophan hydrochloride via a Pictet-Spengler reaction using carbon-11 formaldehyde. J Pept Sci 19:663–668

    Article  CAS  Google Scholar 

  83. Agarwal P, van der Weijden J, Sletten EM, Rabuka D, Bertozzi CR (2013) A Pictet-Spengler ligation for protein chemical modification. Proc Natl Acad Sci U S A 110:46–51

    Article  Google Scholar 

  84. Agarwal P, Kudirka R, Albers AE, Barfield RM, de Hart GW, Drake PM, Jones LC, Rabuka D (2013) Hydrazino-Pictet-Spengler ligation as a biocompatible method for the generation of stable protein conjugates. Bioconjug Chem 24:846–851

    Article  CAS  Google Scholar 

  85. Le Quement ST, Petersen R, Meldal M, Nielsen TE (2010) N-acyliminium intermediates in solid-phase synthesis. Biopolymers (Pept Sci) 94:242–256

    Article  Google Scholar 

  86. Nielsen TE, Diness F, Meldal M (2003) The Pictet-Spengler reaction in solid-phase combinatorial chemistry. Curr Opin Drug Discov Devel 6:801–814

    CAS  Google Scholar 

  87. Pulka K, Feytens D, Misicka A, Tourwé D (2010) New tetracyclic tetrahydro-β-carbolines as tryptophan-derived peptidomimetics. Mol Divers 14:97–108

    Article  CAS  Google Scholar 

  88. Pulka H, Kulis P, Tymecka D, Frankiewicz L, Wilczek M, Kozminski W, Misicka A (2008) Diastereoselective Pictet-Spengler condensation of tryptophan with α-amino aldehydes as chiral carbonyl components. Tetrahedron 64:1506–1514

    Article  CAS  Google Scholar 

  89. Komnatnyy VV, Givskov M, Nielsen TE (2012) Solid-phase synthesis of structurally diverse heterocycles by an amide-ketone condensation/N-acyliminium Pictet-Spengler sequence. Chem Eur J 18:16793–16800

    Article  CAS  Google Scholar 

  90. Dömling A, Ugi I (2000) Multicomponent reactions with isocyanides. Angew Chem Int Ed 39:3168–3210

    Article  Google Scholar 

  91. El Kaim L, Gageat M, Gaultier L, Grimaud L (2007) New Ugi/Pictet-Spengler multicomponent formation of polycyclic diketopiperazines and α-keto acids. Synlett 3:500–502

    Article  Google Scholar 

  92. Liu H, Dömling A (2009) Efficient and diverse synthesis of indole derivatives. J Org Chem 74:6895–6898

    Article  CAS  Google Scholar 

  93. Wang W, Herdtweck E, Dömling A (2010) Polycyclic indole alkaloid-type compounds by MCR. Chem Commun 46:770–772

    Article  CAS  Google Scholar 

  94. Lesma G, Cecchi R, Crippa S, Giovanelli P, Meneghetti F, Musolino M, Sachetti A, Silvani A (2012) Ugi 4-CR/Pictet-Spengler reaction as a short route to tryptophan-derived peptidomimetics. Org Biomol Chem 10:9004–9012

    Article  CAS  Google Scholar 

  95. Sinha MK, Khoury K, Herdtweck E, Dömling A (2013) Tricycles by a new Ugi variation and Pictet-Spengler reaction in one pot. Chem Eur J 19:8048–8052

    Article  CAS  Google Scholar 

  96. Cano-Herrera M-A, Miranda LD (2011) Expedient entry to the piperazinohydroisoquinoline ring system using a sequential Ugi/Pictet-Spengler/reductive methylation reaction protocol. Chem Commun 47:10770–10772

    Article  CAS  Google Scholar 

  97. Airaghi F, Fiorati A, Lesma G, Musolino M, Sacchetti A, Silvani A (2013) The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure. Beilstein J Org Chem 9:147–154

    Article  CAS  Google Scholar 

  98. Petersen R, Le Quement ST, Nielsen TE (2014) Synthesis of a natural product-like compound collection through oxidative cleavage and cyclization of linear peptides. Angew Chem Int Ed 53:11778–11782

    Article  CAS  Google Scholar 

  99. Lesma G, Landoni N, Pilati T, Sacchetti A, Silvani A (2009) Tetrahydroisoquinoline-based spirocyclic lactam as a type II′ β-turn inducing peptide mimetic. J Org Chem 74:8098–8105

    Article  CAS  Google Scholar 

  100. Lesma G, Cecchi R, Cagnotto A, Gobbi M, Meneghetti F, Musolino M, Sacchetti A, Silvani A (2013) Tetrahydro-β-carboline-based spirocyclic lactam as type II′ β-turn: application to the synthesis and biological evaluation of somatostatine mimetics. J Org Chem 78:2600–2610

    Article  CAS  Google Scholar 

  101. Sacchetti A, Silvani A, Lesma G, Pilati T (2011) Phe-Ala-based diazaspirocyclic lactam as nucleator of type II′ β-turn. J Org Chem 76:833–839

    Article  CAS  Google Scholar 

  102. Wünsch B, Zott M (1992) Chirale 2-Benzopyran-3-carbonsäure-Derivate durch Oxa-Pictet-Spengler-Reaktion von (S)-3-Phenylmilchsäure-Derivaten. Liebigs Ann Chem 39–45

    Google Scholar 

  103. Schunk S, Linz K, Frormann S, Hinze C, Oberbörsch S, Sundermann B, Zemolka S, Englberger W, Germann T, Christoph T, Kögel B-Y, Schröder W, Harlfinger S, Saunders D, Kless A, Schick H, Sonnenschein H (2014) Discovery of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amines as potent NOP and opioid receptor agonists. ACS Med Chem Lett 5:851–856

    Article  CAS  Google Scholar 

  104. Schunk S, Linz K, Hinze C, Frormann S, Oberbörsch S, Sundermann B, Zemolka S, Englberger W, Germann T, Christoph T, Kögel B-Y, Schröder W, Harlfinger S, Saunders D, Kless A, Schick H, Sonnenschein H (2014) Discovery of a potent analgesic NOP and opioid receptor agonist: cebranopadol. ACS Med Chem Lett 5:857–862

    Article  CAS  Google Scholar 

  105. Gomez-Monterrey IM, Campiglia P, Bertamino A, Aquino C, Mazzoni O, Diurno MV, Iacovino R, Saviano M, Sala M, Novellino E, Grieco P (2008) Synthesis of novel indole-based ring systems by acid-catalysed condensation from α-amino aldehydes and L-Trp-OMe. Eur J Org Chem 1983–1992

    Google Scholar 

  106. Bai B, Li D-S, Huang S-Z, Ren J, Zhu H-J (2012) Chirality pairing recognition, a unique reaction forming spiral alkaloids from amino acids stereoselectively in one-pot. Nat Prod Bioprospect 2:53–58

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 207, 2800, Kgs. Lyngby, Denmark

    Rico G. Petersen & Vitaly V. Komnatnyy

  2. Protein and Peptide Chemistry, Novo Nordisk A/S, Novo Nordisk Park, 2760, Maaloev, Denmark

    Thomas E. Nielsen

Authors
  1. Rico G. Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vitaly V. Komnatnyy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas E. Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas E. Nielsen .

Editor information

Editors and Affiliations

  1. Départemente de Chimie, Université de Montréal Départemente de Chimie, MONTREAL, Québec, Canada

    William Lubell

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Petersen, R.G., Komnatnyy, V.V., Nielsen, T.E. (2016). Synthesis of Constrained Peptidomimetics via the Pictet-Spengler Reaction. In: Lubell, W. (eds) Peptidomimetics II. Topics in Heterocyclic Chemistry, vol 49. Springer, Cham. https://doi.org/10.1007/7081_2015_190

Download citation

Publish with us

Policies and ethics

Search

Navigation