Romana Pajkert, Sergey Tverdomed and Gerd- Volker Rschenthaler - - PowerPoint PPT Presentation

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Romana Pajkert, Sergey Tverdomed and Gerd- Volker Rschenthaler School of Engineering and Science 22. November 2013 Jacobs University Bremen gGmbH -

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Санкт-Петербургский государственный технологический институт

  • 22. November 2013

Romana Pajkert, Sergey Tverdomed and Gerd-Volker Röschenthaler School of Engineering and Science Jacobs University Bremen gGmbH

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School of Engineering & Science - Chemistry

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Graduation

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  • As a university with the highest standards in research and

teaching, Jacobs University rises to the challenges of today’s globalized world.

  • Our goal is to prepare the leaders of tomorrow to responsibly

meet global challenges.

  • Jacobs students graduate as responsible global citizens

ready to use their acquired skills to make a difference in tomorrow‘s world. Mission Statement

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Bachelor, Master and PhD degrees Performance-oriented admission procedure English as the language of study 1.350 students from 107 countries (739 undergraduates, 16 Foundation Year, 144 Master, 411 PhD, 40 Exchange/Guests) 130 professors, 268 lecturers Student-Professor ratio 10 : 1 Facts

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Alexander Porphyrievich Borodin

Александр Порфирьевич Бородин He was born in 1833 in St. Petersburg, was brought up there with a good

  • education. He got into the Academy of Medicine in St. Petersburg in 1850 where

he studied to become a scientist. From 1864 until his death in 1887, he was a professor of chemistry at the St. Petersburg Military Academy; he both taught and did research.

.

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  • Ann. Chem. Pharm. 126 (1863) 58-62.
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10

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Hennig Brand (1630–1710) was a merchant and amateur alchemist in Hamburg who discovered phosphorus around 1669. The Alchemist in Search

  • f

the Philosophers Stone (1771) by Joseph Wright depicting Hennig Brand discovering phosphorus (the glow shown is exaggerated)

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2-Aminoethylphosphonic Acid (AEP, Ciliatine) Phosphonothricin. Application of Phosphorus Compounds:

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13

Carbamoyl- phosphonates Amino- phosphonates

Difluoromethylene phosphonates

Phosphono- carboxylates

Aromatic and heteroaromatic phosphonates

BIOLOGICALLY RELEVANT PHOSPHONATES

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Carbamoyl- phosphonates

Difluoromethylene phosphonates

Phosphono- carboxylates

Aromatic and heteroaromatic phosphonates

BIOLOGICALLY RELEVANT PHOSPHONATES Bisphosphonates Amino- phosphonates

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SLIDE 15

RELEVANCE BIOLOGICALLY ACTIVE AMINOPHOSPHONATES

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Cytotoxic Aminophosphonates with a 3,5-Bis(arylidene)piperid-4-one Framework

M.V. Makarov, E.Yu. Rybalkina, G.-V. Röschenthaler, K.W. Short,T.V.Timofeeva, I.

  • L. Odinets, Eur. J. Med. Chem. 2009, 44, 2135-2144.
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Substituted Cyclic α-Aminophosphonates

I.L. Odinets, O.I. Artyushin, N. Shevchenko, P. V. Petrovskii, V. G. Nenajdenko, G.-V. Röschenthaler, Synthesis 2009, 577-582.

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Novel N-Phosphonoformyl Derivatives of α-CF3-α-Amino Acids

  • H. Skarpos, D.V. Vorob’eva, S.N. Osipov, I.L. Odinets, E. Breuer, G.-V.

Röschenthaler, Org. Biomol. Chem. 2006, 4, 3669-3674.

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Novel N-Phosphonoformyl Derivatives of α-CF3-α-Amino Acids

  • H. Skarpos, D.V. Vorob’eva, S.N. Osipov, I.L. Odinets, E. Breuer, G.-V.

Röschenthaler, Org. Biomol. Chem. 2006, 4, 3669-3674.

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Novel N-Phosphonoformyl Derivatives of α-CF3-α-Amino Acids

  • H. Skarpos, D.V. Vorob’eva, S.N. Osipov, I.L. Odinets, E. Breuer, G.-V.

Röschenthaler, Org. Biomol. Chem. 2006, 4, 3669-3674.

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SLIDE 21

Carbamoyl- phosphonates

Difluoromethylene phosphonates

Phosphono- carboxylates

Aromatic and heteroaromatic phosphonates

BIOLOGICALLY RELEVANT PHOSPHONATES Bisphosphonates Amino- phosphonates

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SLIDE 22

Chambers R.D.; O’Hagan D.; Lamont B.; Jain S.C. J. Chem. Soc. Chem.Commun. 1990, 1053

  • D. O’Hagan, H.S. Rzepa Chem. Commun. 1997, 645

CHEMISTRY

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BIOLOGICALLY ACTIVE DIFLUOROMETHYLENEPHOSPHONATES

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Difluoro(diethoxyphosphoryl)acetyl Chloride – Synthesis and Amination

  • R. Pajkert, M. Milewska, G.-V. Röschenthaler, H. Koroniak,
  • J. Fluorine Chem. 2009, 130, 695-701.
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Novel α-CF3-Amino Acids Derivatives Bearing N-(β-keto-α,α-difluoromethylenephosphonate) Moiety

  • R. Pajkert, G.-V. Röschenthaler, J. Fluorine Chem. 2010, 131, 1362-1367.
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Novel α-CF3-Amino Acids Derivatives Bearing N-(β-keto-α,α-difluoromethylenephosphonate) Moiety

  • R. Pajkert, G.-V. Röschenthaler, J. Fluorine Chem. 2010, 131, 1362-1367.
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Difluoropropargyl Phosphonates via Aldehyde-to-Alkyne Homologation

  • R. Pajkert, G.-V. Röschenthaler, J. Org. Chem. 2013, 78, 3697-3708.
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Difluoropropargyl Phosphonates via Aldehyde-to-Alkyne Homologation

  • R. Pajkert, G.-V. Röschenthaler, J. Org. Chem. 2013, 78, 3697-3708.
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Transannular Cyclization of 3,7-Dimethylenebicyclo[3.3.1]nonane with Difuoromethylenephosphonic Radical

M.V. Ponomarenko, Y.A. Serguchev, B.V. Ponomarenko, G.-V. Röschenthaler, A.A. Fokin, J. Fluorine Chem. 2006, 127, 842-849.

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30

Carbamoyl- phosphonates

Difluoromethylene phosphonates

Phosphono- carboxylates

Aromatic and heteroaromatic phosphonates

BIOLOGICALLY RELEVANT PHOSPHONATES Bisphosphonates Amino- phosphonates

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Carbamoylphosphonate-Based Matrix Metalloproteinase (MMPs) Inhibitor Metal Complexes

  • E. Farkas, Y. Katz, S. Bhusare, R. Reich, G.-V. Röschenthaler, M. Königsmann, E.

Breuer, J. Biol. Inorg. Chem. 2004, 9, 307-315; E. Breuer, C.J. Salomon, Y. Katz,

  • W. Chen, Shuiming Lu, G.-V. Röschenthaler, R. Hadar, R. Reich, J. Med. Chem.

2004, 47, 2826-2832.

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Carbamoylphosphonate-Based Matrix Metalloproteinase (MMPs) Inhibitor Metal Complexes

  • E. Farkas, Y. Katz, S. Bhusare, R. Reich, G.-V. Röschenthaler, M. Königsmann, E.

Breuer, J. Biol. Inorg. Chem. 2004, 9, 307-315.

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SLIDE 33

33

Carbamoyl- phosphonates Amino- phosphonates

Difluoromethylene phosphonates

Phosphono- carboxylates

Aromatic and heteroaromatic phosphonates

BIOLOGICALLY RELEVANT PHOSPHONATES Bisphosphonates

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SLIDE 34

RELEVANCE

BIOLOGICALLY ACTIVE AROMATIC AND HETEROAROMATIC PHOSPHONATES

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Synthetic Strategies towards ortho-Fluoro substituted Carbo- and Heterocyclic Phosphonates

  • B. Duda, S. N. Tverdomed, G.-V. Röschenthaler, J. Fluorine Chem.,

2013, 152, 29-37.

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Synthesis of Fluorinated Alkynephosphonates

  • S. N. Tverdomed, G.-V. Röschenthaler, N. Kalinovich, E. Lork, A. V. Dogadina, B. I. Ionin,
  • J. Fluorine Chem. 2008, 129, 478-485; S.N. Tverdomed, J. Kolanowski, G.-V.

Röschenthaler, Tetrahedron 2011, 67, 3887-3901.

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New α-Substituted Alkylbenzene- and Dialkylbenzene- 1,2-diphosphonates

  • S. N. Tverdomed, A. V. Dogadina, B. I. Ionin Russ. J. Gen. Chem. 2006, 76, 885-894;
  • S. N. Tverdomed, G.-V. Röschenthaler, N. Kalinovich, E. Lork, A. V. Dogadina,
  • B. I. Ionin, Tetrahedron. 2008, 64, 5306-5313.
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New α-Substituted Alkylbenzene- and Dialkylbenzene- 1,2-diphosphonates

  • S. N. Tverdomed, G.-V. Röschenthaler, N. Kalinovich, E. Lork, A. V. Dogadina, B.
  • I. Ionin, Tetrahedron. 2008, 64, 5306-5313.
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New α-Substituted Alkylbenzene- and Dialkylbenzene- 1,2-diphosphonates

  • S. N. Tverdomed, G.-V. Röschenthaler, N. Kalinovich, E. Lork, A. V. Dogadina, B. I.

Ionin, J. Fluorine Chem. 2008, 129, 478-485.

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Perfluoroacetylenephosphonates in Diels-Alder Reactions

C19 O2 C18 C21 C6 C12 O3 C20 C13 C11 P1 C1 C8 O1 C10 C3 C2 C9 F1 C7 F2 F3

P F O C H
  • S. N. Tverdomed, G.-V. Röschenthaler, N. Kalinovich, E. Lork, A. V. Dogadina, B.
  • I. Ionin, J. Fluorine Chem. 2008, 129, 478-485.
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  • rtho-Difluoromethyl Arylphosphonates:

Reactivity of Phosphorus- and Fluorine-containing Functions

S.N. Tverdomed, J. Kolanowski, G.-V. Röschenthaler, Tetrahedron 2011, 67, 3887-3901.

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SLIDE 42
  • rtho-Difluoromethyl Arylphosphonates:

Reactivity of Phosphorus- and Fluorine-containing Functions

S.N. Tverdomed, J. Kolanowski, G.-V. Röschenthaler, Tetrahedron 2011, 67, 3887-3901.

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XCF2-Containing Azaxanth-3-yl and Quinolin-3-yl Phosphonates

  • B. Duda, S N. Tverdomed, G.-V. Röschenthaler, Org. Biomol.
  • Chem. 2011, 9, 8228-8232; B. Duda, S. N. Tverdomed, G.-V.

Röschenthaler, RSC Adv. 2012, 2, 9135-9141.

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4-Aminoquinolin-3-ylphosphonates

  • B. Duda, S. N. Tverdomed, B I. Ionin, G.-V. Röschenthaler, Eur. J. Org. Chem.

2012, 3684-3690.

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SLIDE 45
  • B. Duda, S. N. Tverdomed, B I. Ionin, G.-V. Röschenthaler, Eur. J. Org. Chem.

2012, 3684-3690.

4-Aminoquinolin-3-ylphosphonates

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Polysubstituted Fluorinated Arylphosphonates

  • S. Tverdomed, B. Duda, G.-V. Röschenthaler (Jacobs University Bremen),

Patent DE 102012104007.9, 2012.

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SLIDE 47

2-Perfluoroalkyl 4H- and 2H-chromenylphosphonates

  • B. Duda, S. N. Tverdomed, G.-V. Röschenthaler, J. Org. Chem. 2011, 76, 71-79.
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SLIDE 48

Carbamoyl- phosphonates Amino- phosphonates

Difluoromethylene phosphonates

Phosphono- carboxylates BIOLOGICALLY RELEVANT PHOSPHONATES

Aromatic and heteroaromatic phosphonates

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SLIDE 49
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SLIDE 50
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SLIDE 51
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SLIDE 52
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SLIDE 53
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SLIDE 54

54

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SLIDE 55

55

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~ 1 x Etidronate ~ 10 x Clodronate Tiludronate ~ 100 x Neridronate Pamidronate > 100 – < 1000 x Alendronate Incadronate Olpadronate > 1000 – < 10 000 x Ibandronate Risendronate > 10 000 x Zolendronate

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SLIDE 57
  • M. V. Makarov, E. S. Leonova, E. Yu. Rybalkina, V. N. Khrustalev, N. E. Shepel, G.-V.

Röschenthaler, T. V. Timofeeva, I. L. Odinets, Arch. Pharm. Chem. Life Sci. 2012, 345, 349–359.

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SLIDE 58
  • H. Skarpos, S.N. Osipov, D.V. Vorob’eva, I.L. Odinets, E. Lork, G.-V. Röschenthaler,
  • Org. Biomol. Chem., 2007, 5, 2361–2367.
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SLIDE 59
  • H. Skarpos, S.N. Osipov, D.V. Vorob’eva, I.L. Odinets, E. Lork, G.-V. Röschenthaler,
  • Org. Biomol. Chem., 2007, 5, 2361–2367.
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SLIDE 60

R.-M. Schoth, E. Lork, F.U. Seifert, G.-V. Röschenthaler, Naturwissenschaften 1996, 83, 571-574

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SLIDE 61
  • A. Banerjee, B. S. Bassil, G.-V. Röschenthaler, U. Kortz, Eur. J. Inorg. Chem.

2010, 3915–3919; Chem. Soc. Rev. 2012, 7590-7604

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SLIDE 62
  • W. Greb, O. Shyshkov, G.-V. Röschenthaler, V. Hengst, US 20070154537 A1, 2007;
  • V. Hengst, C. Oussoren, T. Kissel, G. Storm, Int. J. Pharm. 2007, 331, 224–227.
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SLIDE 63
  • W. Greb, O. Shyshkov, G.-V. Röschenthaler, V. Hengst, US 20070154537 A1, 2007; V.

Hengst, C. Oussoren, T. Kissel, G. Storm, Int. J. Pharm. 2007, 331, 224–227.

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SLIDE 64
  • W. Greb, O. Shyshkov, G.-V.

Röschenthaler, V. Hengst, US 20070154537, 2007; V. Hengst, C. Oussoren, T. Kissel, G. Storm, Int. J.

  • Pharm. 2007, 331, 224–227.
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SLIDE 65

G.-V. Röschenthaler, K. Vlasov, D. L. Chizhov, V. N. Charushin, K. Burger, Tetrahedron Lett. in press

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SLIDE 66

G.-V. Röschenthaler, K. Vlasov, D. L. Chizhov, V. N. Charushin, K. Burger, Tetrahedron Lett. in press

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SLIDE 67
  • K. Vlasov, Neue fluorierte Sulfonate, Amine und Phosphonate: Synthese und

mögliche Anwendungen, PhD Thesis, University of Bremen, 2010.

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SLIDE 68
  • K. Vlasov, Neue fluorierte Sulfonate, Amine und Phosphonate: Synthese und

mögliche Anwendungen, PhD Thesis, University of Bremen, 2010.

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SLIDE 69
  • H. Blum, W. Greb, Y. Pustovit, G.-V. Röschenthaler, Patent US 20040087554, 2004
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SLIDE 70

Bisphosphonates Carbamoyl- phosphonates Amino- phosphonates

Difluoromethylene phosphonates

Phosphono- carboxylates BIOLOGICALLY RELEVANT PHOSPHONATES

Aromatic and heteroaromatic phosphonates

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SLIDE 71

RELEVANCE BIOLOGICALLY ACTIVE PHOSPHONOCARBOXYLATES

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SLIDE 72

Click Chemistry of Propargyl-Substituted Phosphonocarboxylates

O.I. Artyushin, S. N. Osipov, G.-V. Röschenthaler, I. L. Odinets, Synthesis 2009, 3579-3588.

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SLIDE 73

Click Chemistry of Propargyl-Substituted Phosphonocarboxylates

O.I. Artyushin, S. N. Osipov, G.-V. Röschenthaler, I. L. Odinets, Synthesis 2009, 3579-3588.

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SLIDE 74

Methyl 2-[Bis(trimethylsiloxy)phosphoryl]-3,3,3-trifluoro- 2-(trimethylsiloxy)propionate and Some Derivatives

R.-M. Schoth, E. Lork, F.U. Seifert, E. Breuer, G.-V. Röschenthaler, Chem. Ber./Recueil 1997,130,279-281.

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SLIDE 75

Acknowledgements

  • Dr. Max Braun, Dr. Johannes Eicher, Solvay Fluor GmbH Hannover, Germany
  • Dr. Detlef Pauluth, Dr. Matthias Bremer, Prof. Peer Kirsch, Merck KGaA, Darmstadt,

Germany

  • Dr. Tobias Böttcher, Dr. Bassem Bassil, Dr. Blazej Duda, Dr. Jolanta Ignatowska, Dr.

Lesley Lewis-Alleyne, Dr. Nataliya Kalinovich, Dr. Olesya Kazakova, Dr. Romana Pajkert, Dr. Maxim Ponomarenko, Dr. Sergey Tverdomed, Dr. Katja Vlasov

DFG, BMWi, Merck KGaA, Dyneon 3M, Solvay Fluor

  • Prof. Valentine Nenajdenko, Moscow State University; Profs Irina Odinets and Sergey

Osipov, Nesmeyanov Institute, Russian Academy of Sciences, Moscow, Russia

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SLIDE 76

Acknowledgements

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SLIDE 77

Благодарю за внимание