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

Romana Pajkert, Sergey Tverdomed and Gerd- Volker Röschenthaler School of Engineering and Science 22. November 2013 Jacobs University Bremen gGmbH Санкт - Петербургский государственный технологический институт

School of Engineering & Science - Chemistry

Graduation

Mission Statement • 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.

Facts 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

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. .

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

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(1630 – 1710) Hennig Brand was a merchant and amateur alchemist in Hamburg who discovered phosphorus around 1669. The Alchemist in Search of the Philosophers Stone (1771) by Joseph Wright depicting Hennig Brand discovering phosphorus (the glow shown is exaggerated)

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

Amino- Difluoromethylene phosphonates phosphonates B IOLOGICALLY Phosphono- Carbamoyl- R ELEVANT carboxylates phosphonates P HOSPHONATES Aromatic and heteroaromatic phosphonates 13

Amino- Difluoromethylene phosphonates phosphonates B IOLOGICALLY Phosphono- Carbamoyl- R ELEVANT carboxylates phosphonates P HOSPHONATES Aromatic and heteroaromatic Bisphosphonates phosphonates 14

R ELEVANCE B IOLOGICALLY A CTIVE A MINOPHOSPHONATES

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.

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. 17

Novel N -Phosphonoformyl Derivatives of α -CF 3 - 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.

Novel N -Phosphonoformyl Derivatives of α -CF 3 - 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.

Novel N -Phosphonoformyl Derivatives of α -CF 3 - 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.

Amino- Difluoromethylene phosphonates phosphonates B IOLOGICALLY Phosphono- Carbamoyl- R ELEVANT carboxylates phosphonates P HOSPHONATES Aromatic and heteroaromatic Bisphosphonates phosphonates

CHEMISTRY 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

BIOLOGICALLY ACTIVE DIFLUOROMETHYLENEPHOSPHONATES

Difluoro(diethoxyphosphoryl)acetyl Chloride – Synthesis and Amination R. Pajkert, M. Milewska, G.- V. Röschenthaler, H. Koroniak, J. Fluorine Chem . 2009 , 130 , 695-701.

Novel α -CF 3 -Amino Acids Derivatives Bearing N -( β -keto- α , α -difluoromethylenephosphonate) Moiety R. Pajkert, G.- V. Röschenthaler, J. Fluorine Chem. 2010 , 131 , 1362-1367.

Novel α -CF 3 -Amino Acids Derivatives Bearing N -( β -keto- α , α -difluoromethylenephosphonate) Moiety R. Pajkert, G.- V. Röschenthaler, J. Fluorine Chem. 2010 , 131 , 1362-1367.

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

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

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.

Amino- Difluoromethylene phosphonates phosphonates B IOLOGICALLY Phosphono- Carbamoyl- R ELEVANT carboxylates phosphonates P HOSPHONATES Aromatic and heteroaromatic Bisphosphonates phosphonates 30

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.

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.

Amino- Difluoromethylene phosphonates phosphonates B IOLOGICALLY Phosphono- Carbamoyl- R ELEVANT carboxylates phosphonates P HOSPHONATES Aromatic and Bisphosphonates heteroaromatic phosphonates 33

R ELEVANCE B IOLOGICALLY A CTIVE A ROMATIC AND H ETEROAROMATIC P HOSPHONATES

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.

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.

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.

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.

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.

Perfluoroacetylenephosphonates in Diels-Alder Reactions C11 C10 C12 C9 C21 C13 C8 C20 C3 O3 C6 C1 F2 C2 P1 F3 C7 P O1 O2 F1 F C18 O C H C19 S. N. Tverdomed, G.- V. Röschenthaler, N. Kalinovich, E. Lork, A. V. Dogadina, B. I. Ionin, J. Fluorine Chem . 2008 , 129 , 478-485.

ortho -Difluoromethyl Arylphosphonates: Reactivity of Phosphorus- and Fluorine-containing Functions S.N. Tverdomed, J. Kolanowski, G.- V. Röschenthaler, Tetrahedron 2011 , 67 , 3887-3901.

ortho -Difluoromethyl Arylphosphonates: Reactivity of Phosphorus- and Fluorine-containing Functions S.N. Tverdomed, J. Kolanowski, G.- V. Röschenthaler, Tetrahedron 2011 , 67 , 3887-3901.

XCF 2 -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.

4-Aminoquinolin-3-ylphosphonates B. Duda, S. N. Tverdomed, B I. Ionin, G.- V. Röschenthaler, Eur. J. Org. Chem . 2012 , 3684-3690.

4-Aminoquinolin-3-ylphosphonates B. Duda, S. N. Tverdomed, B I. Ionin, G.- V. Röschenthaler, Eur. J. Org. Chem . 2012 , 3684-3690.

Polysubstituted Fluorinated Arylphosphonates S. Tverdomed, B. Duda, G.- V. Röschenthaler (Jacobs University Bremen), Patent DE 102012104007.9, 2012.

2-Perfluoroalkyl 4 H - and 2 H -chromenylphosphonates B. Duda, S. N. Tverdomed, G.- V. Röschenthaler, J. Org. Chem . 2011 , 76 , 71-79.

Amino- Difluoromethylene phosphonates phosphonates B IOLOGICALLY Phosphono- Carbamoyl- R ELEVANT carboxylates phosphonates P HOSPHONATES Aromatic and heteroaromatic phosphonates

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> 100 – > 1000 – ~ 1 x ~ 10 x ~ 100 x > 10 000 x < 1000 x < 10 000 x Etidronate Clodronate Neridronate Alendronate Ibandronate Zolendronate Tiludronate Pamidronate Incadronate Risendronate Olpadronate 56

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.