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John R. Falck

November 25, 2023

John Russell “Camille” Falck (born December 2, 1948) is an American chemist, Professor of Biochemistry, and holder of the Robert A. Welch Distinguish Chair in Chemistry at the University of Texas Southwestern Medical Center (UT SW Medical Center).[1] In 1996 he was awarded the Wilfred T. Doherty Recognition Award from the Dallas-Forth Worth Section of the American Chemical Society [2] and a Recognition Award at the March 10, 2002, Winter Eicosanoid Conference (Baltimore MD) in appreciation of his significant contributions to the chemistry of natural products, and to the identification and functional characterization of the cytochrome P450 (P450) arachidonic acid (AA) monooxygenase metabolic pathway and its metabolites.[3]

Early life and career edit

Falck was born in the then US territory of Alaska, married Elaine R. Fogel (died 9/2008), and has two sons Benjamin and Aaron. He earned a BSc and PhD in organic chemistry from Colorado State University in 1970 and 1973, and a Diploma of Imperial College (DIC), London, England. After postdoctoral studies with Nobel laurates Derek H. R. Barton (Imperial College, London) and Elias J. Corey (Harvard University, MA) he joined the faculty at the then University of Texas Health Science Center (now UT SW Medical Center) in 1979. Falck has authored more than 820 peer-reviewed publications and awarded 40 patents.

Scientific contributions edit

P450 AA monooxygenases edit

Following initial reports of AA metabolism by P450 enzymes, Falck completed the first structural characterization and synthesis of 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids (EETs) and of 19- and 20-hydroxyeicosatetraenoic acids (19- and 20-HETEs), and characterized them as products of the epoxygenase and ω/ω-1 hydroxylase branches of the P450 AA Monooxygenase, respectively.[4][5] These synthetic achievements were followed by Falck’s early contributions to the: a) development of analytical methods for the identification of EETs and 19- and 20-HETE as products of endogenous metabolism of AA by P450 enzymes,[6][7][8][9] b) establishment of the P450 AA Monooxgenase as a branch of the AA metabolic cascade,[3][4][8] and c) characterization of biological activities associated with many of the P450 metabolites.[3][4] These accomplishments, highlighted in independent reviews,[10][11][12][13] were followed by Falck’s development of synthetic EET and 20-HETE functional analogs/antagonists, which were of critical importance during the subsequent characterization of physiological and pathophysiological roles for these enzymes and their metabolites.[14][15][16]

Total syntheses edit

Falck is known for his application of efficient, eco-friendly chemical procedures and/or strategies during the synthesis of a wide range of drug candidates, several of which are currently undergoing clinical evaluation. He has also confirmed the structures of several bioactive compounds found in natural products, and of short-lived intracellular second messengers that mediated cellular responses to environmental stimuli.

Development of chemical and biochemical techniques and tools edit

Falck’s contributions range from practical methods for creating carbon-carbon,[17][18] carbon-nitrogen,[19][20][21] and carbon-oxygen [22] bonds to the visualization of acidic organelles inside cells.[23] He is also distinguished for developing the Falck-Bradsher annulation [24] used to prepare six-membered rings containing a nitrogen based upon a process chemists call an inverse electron demand [4+2]-cycloaddition.

References edit

  1. ^ "J Falck, Ph.D. - Faculty Profile - UT Southwestern". profiles.utsouthwestern.edu.
  2. ^ Section, American Chemical Society Dallas/Fort Worth; Strom, E. Thomas (April 16, 1996). "Southwest Retort, Volume 49, Number 8, April 1996". Southwest Retort. 49 (8) – via digital.library.unt.edu.
  3. ^ a b c Capdevila, Jorge H.; Falck, John R. (1 November 2018). "Thematic Review Series: Living History of Lipids The arachidonic acid monooxygenase: from biochemical curiosity to physiological/pathophysiological significance". Journal of Lipid Research. 59 (11): 2047–2062. doi:10.1194/jlr.R087882. ISSN 0022-2275. PMC 6210905. PMID 30154230.
  4. ^ a b c Moustakis, Christine A.; Viala, Jacques; Capdevila, Jorge; Falck, J. R. (September 1985). "Total synthesis of the cytochrome P-450 epoxygenase metabolites 5(R),6(S)-, 5(S),6(R)-, and 14(R),15(S)-epoxyeicosatrienoic acid (EET) and hydration products 5(R),6(R)- and 14(R),15(R)-dihydroxyeicosatrienoic acid (DHET)". Journal of the American Chemical Society. 107 (18): 5283–5285. doi:10.1021/ja00304a048. ISSN 0002-7863.
  5. ^ Capdevila, JH; Falck, JR; Harris, RC (February 2000). "Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase". Journal of Lipid Research. 41 (2): 163–81. doi:10.1016/S0022-2275(20)32049-6. PMID 10681399.
  6. ^ Gopal, V. Raj; Jagadeesh, S. G.; Reddy, Y. Krishna; Bandyopadhyay, A.; Capdevila, Jorge H.; Falck, J. R. (15 March 2004). "A practical, stereospecific route to 18-, 19-, and 20-hydroxyeicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acids (18-, 19-, and 20-HETEs)". Tetrahedron Letters. 45 (12): 2563–2565. doi:10.1016/j.tetlet.2004.01.151. ISSN 0040-4039.
  7. ^ Capdevila, Jorge H.; Wei, Shouzou; Kumar, Anil; Kobayashi, Jun; Snapper, James R.; Zeldin, Darryl C.; Bhatt, Rama K.; Falck, John R. (1 December 1992). "Resolution of dihydroxyeicosanoates and of dihydroxyeicosatrienoates by chiral phase chromatography". Analytical Biochemistry. 207 (2): 236–240. doi:10.1016/0003-2697(92)90006-S. ISSN 0003-2697. PMID 1481976.
  8. ^ a b Karara, A; Dishman, E; Blair, I; Falck, JR; Capdevila, JH (25 November 1989). "Endogenous epoxyeicosatrienoic acids. Cytochrome P-450 controlled stereoselectivity of the hepatic arachidonic acid epoxygenase". The Journal of Biological Chemistry. 264 (33): 19822–7. doi:10.1016/S0021-9258(19)47185-8. PMID 2584196.
  9. ^ Zeldin, DC; Kobayashi, J; Falck, JR; Winder, BS; Hammock, BD; Snapper, JR; Capdevila, JH (25 March 1993). "Regio- and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase". The Journal of Biological Chemistry. 268 (9): 6402–7. doi:10.1016/S0021-9258(18)53266-X. PMID 8454612.
  10. ^ McGiff, John C.; Quilley, John (March 2001). "20-Hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids and blood pressure". Current Opinion in Nephrology and Hypertension. 10 (2): 231–237. doi:10.1097/00041552-200103000-00012. ISSN 1062-4821. PMID 11224699. S2CID 44774278.
  11. ^ Roman, RJ (January 2002). "P-450 metabolites of arachidonic acid in the control of cardiovascular function". Physiological Reviews. 82 (1): 131–85. doi:10.1152/physrev.00021.2001. PMID 11773611.
  12. ^ Pfister, Sandra L.; Gauthier, Kathryn M.; Campbell, William B. (1 January 2010). "Vascular Pharmacology of Epoxyeicosatrienoic Acids". Chapter 2 - Vascular Pharmacology of Epoxyeicosatrienoic Acids. Advances in Pharmacology. Vol. 60. Academic Press. pp. 27–59. doi:10.1016/b978-0-12-385061-4.00002-7. ISBN 9780123850614. PMC 3373307. PMID 21081214.
  13. ^ Imig, John D. (1 July 2013). "Epoxyeicosatrienoic acids, 20-hydroxyeicosatetraenoic acid, and renal microvascular function". Prostaglandins & Other Lipid Mediators. 104–105: 2–7. doi:10.1016/j.prostaglandins.2013.01.002. ISSN 1098-8823. PMC 3664103. PMID 23333581.
  14. ^ Alonso-Galicia, Magdalena; Falck, John R.; Reddy, Komandla Malla; Roman, Richard J. (1 November 1999). "20-HETE agonists and antagonists in the renal circulation". American Journal of Physiology. Renal Physiology. 277 (5): F790–F796. doi:10.1152/ajprenal.1999.277.5.F790. ISSN 1931-857X. PMID 10564244.
  15. ^ Falck, JR; Koduru, SR; Mohapatra, S; Manne, R; Atcha, KR; Atcha, R; Manthati, VL; Capdevila, JH; Christian, S; Imig, JD; Campbell, WB (28 August 2014). "14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates: carboxylate modifications". Journal of Medicinal Chemistry. 57 (16): 6965–72. doi:10.1021/jm500262m. PMC 4148164. PMID 25119815.
  16. ^ Campbell, William B.; Imig, John D.; Schmitz, James M.; Falck, John R. (October 2017). "Orally Active Epoxyeicosatrienoic Acid Analogs". Journal of Cardiovascular Pharmacology. 70 (4): 211–224. doi:10.1097/FJC.0000000000000523. ISSN 0160-2446. PMC 5673125. PMID 28937442.
  17. ^ Falck, J. R.; Bhatt, Rama K.; Ye, Jianhua (June 1995). "Tin-Copper Transmetalation: Cross-Coupling of .alpha.-Heteroatom-Substituted Alkyltributylstannanes with Organohalides". Journal of the American Chemical Society. 117 (22): 5973–5982. doi:10.1021/ja00127a010. ISSN 0002-7863.
  18. ^ Ye, Jianhua; Bhatt, Rama K.; Falck, J. R. (10 December 1993). "Stereospecific α-alkoxystannane couplings with acyl chlorides: Total synthesis of (+)-goniofufurone". Tetrahedron Letters. 34 (50): 8007–8010. doi:10.1016/S0040-4039(00)61436-3. ISSN 0040-4039.
  19. ^ Jat, Jawahar L.; Paudyal, Mahesh P.; Gao, Hongyin; Xu, Qing-Long; Yousufuddin, Muhammed; Devarajan, Deepa; Ess, Daniel H.; Kürti, László; Falck, John R. (3 January 2014). "Direct Stereospecific Synthesis of Unprotected N-H and N-Me Aziridines from Olefins". Science. 343 (6166): 61–65. Bibcode:2014Sci...343...61J. doi:10.1126/science.1245727. ISSN 0036-8075. PMC 4175444. PMID 24385626.
  20. ^ Paudyal, Mahesh P.; Adebesin, Adeniyi Michael; Burt, Scott R.; Ess, Daniel H.; Ma, Zhiwei; Kürti, László; Falck, John R. (9 September 2016). "Dirhodium-catalyzed C-H arene amination using hydroxylamines". Science. 353 (6304): 1144–1147. Bibcode:2016Sci...353.1144P. doi:10.1126/science.aaf8713. ISSN 0036-8075. PMC 5040325. PMID 27609890.
  21. ^ Anugu, Raghunath Reddy; Munnuri, Sailu; Falck, John R. (18 March 2020). "Picolinate-Directed Arene meta -C–H Amination via FeCl 3 Catalysis". Journal of the American Chemical Society. 142 (11): 5266–5271. doi:10.1021/jacs.9b13753. ISSN 0002-7863. PMID 32090542. S2CID 211262974.
  22. ^ Falck, J.R.; Yu, Jurong; Cho, Hyun-Sung (August 1994). "A convenient synthesis of unsymmetric polyfluoroethers". Tetrahedron Letters. 35 (33): 5997–6000. doi:10.1016/0040-4039(94)88058-1.
  23. ^ Anderson, R G; Falck, J R; Goldstein, J L; Brown, M S (August 1984). "Visualization of acidic organelles in intact cells by electron microscopy". Proceedings of the National Academy of Sciences. 81 (15): 4838–4842. Bibcode:1984PNAS...81.4838A. doi:10.1073/pnas.81.15.4838. ISSN 0027-8424. PMC 391586. PMID 6146980.
  24. ^ Bolitt, Veronique; Mioskowski, Charles; Kollah, R. Ominde; Manna, Sukumar; Rajapaksa, D.; Falck, J. R. (July 1991). "Total synthesis of vineomycinone B2 methyl ester via double Bradsher cyclization". Journal of the American Chemical Society. 113 (16): 6320–6321. doi:10.1021/ja00016a086. ISSN 0002-7863.

November 25, 2023
john, falck, john, russell, camille, falck, born, december, 1948, american, chemist, professor, biochemistry, holder, robert, welch, distinguish, chair, chemistry, university, texas, southwestern, medical, center, medical, center, 1996, awarded, wilfred, doher. John Russell Camille Falck born December 2 1948 is an American chemist Professor of Biochemistry and holder of the Robert A Welch Distinguish Chair in Chemistry at the University of Texas Southwestern Medical Center UT SW Medical Center 1 In 1996 he was awarded the Wilfred T Doherty Recognition Award from the Dallas Forth Worth Section of the American Chemical Society 2 and a Recognition Award at the March 10 2002 Winter Eicosanoid Conference Baltimore MD in appreciation of his significant contributions to the chemistry of natural products and to the identification and functional characterization of the cytochrome P450 P450 arachidonic acid AA monooxygenase metabolic pathway and its metabolites 3 Contents 1 Early life and career 2 Scientific contributions 2 1 P450 AA monooxygenases 2 2 Total syntheses 2 3 Development of chemical and biochemical techniques and tools 3 ReferencesEarly life and career editFalck was born in the then US territory of Alaska married Elaine R Fogel died 9 2008 and has two sons Benjamin and Aaron He earned a BSc and PhD in organic chemistry from Colorado State University in 1970 and 1973 and a Diploma of Imperial College DIC London England After postdoctoral studies with Nobel laurates Derek H R Barton Imperial College London and Elias J Corey Harvard University MA he joined the faculty at the then University of Texas Health Science Center now UT SW Medical Center in 1979 Falck has authored more than 820 peer reviewed publications and awarded 40 patents Scientific contributions editP450 AA monooxygenases edit Following initial reports of AA metabolism by P450 enzymes Falck completed the first structural characterization and synthesis of 5 6 8 9 11 12 and 14 15 epoxyeicosatrienoic acids EETs and of 19 and 20 hydroxyeicosatetraenoic acids 19 and 20 HETEs and characterized them as products of the epoxygenase and w w 1 hydroxylase branches of the P450 AA Monooxygenase respectively 4 5 These synthetic achievements were followed by Falck s early contributions to the a development of analytical methods for the identification of EETs and 19 and 20 HETE as products of endogenous metabolism of AA by P450 enzymes 6 7 8 9 b establishment of the P450 AA Monooxgenase as a branch of the AA metabolic cascade 3 4 8 and c characterization of biological activities associated with many of the P450 metabolites 3 4 These accomplishments highlighted in independent reviews 10 11 12 13 were followed by Falck s development of synthetic EET and 20 HETE functional analogs antagonists which were of critical importance during the subsequent characterization of physiological and pathophysiological roles for these enzymes and their metabolites 14 15 16 Total syntheses edit Falck is known for his application of efficient eco friendly chemical procedures and or strategies during the synthesis of a wide range of drug candidates several of which are currently undergoing clinical evaluation He has also confirmed the structures of several bioactive compounds found in natural products and of short lived intracellular second messengers that mediated cellular responses to environmental stimuli Development of chemical and biochemical techniques and tools edit Falck s contributions range from practical methods for creating carbon carbon 17 18 carbon nitrogen 19 20 21 and carbon oxygen 22 bonds to the visualization of acidic organelles inside cells 23 He is also distinguished for developing the Falck Bradsher annulation 24 used to prepare six membered rings containing a nitrogen based upon a process chemists call an inverse electron demand 4 2 cycloaddition References edit J Falck Ph D Faculty Profile UT Southwestern profiles utsouthwestern edu Section American Chemical Society Dallas Fort Worth Strom E Thomas April 16 1996 Southwest Retort Volume 49 Number 8 April 1996 Southwest Retort 49 8 via digital library unt edu a b c Capdevila Jorge H Falck John R 1 November 2018 Thematic Review Series Living History of Lipids The arachidonic acid monooxygenase from biochemical curiosity to physiological pathophysiological significance Journal of Lipid Research 59 11 2047 2062 doi 10 1194 jlr R087882 ISSN 0022 2275 PMC 6210905 PMID 30154230 a b c Moustakis Christine A Viala Jacques Capdevila Jorge Falck J R September 1985 Total synthesis of the cytochrome P 450 epoxygenase metabolites 5 R 6 S 5 S 6 R and 14 R 15 S epoxyeicosatrienoic acid EET and hydration products 5 R 6 R and 14 R 15 R dihydroxyeicosatrienoic acid DHET Journal of the American Chemical Society 107 18 5283 5285 doi 10 1021 ja00304a048 ISSN 0002 7863 Capdevila JH Falck JR Harris RC February 2000 Cytochrome P450 and arachidonic acid bioactivation Molecular and functional properties of the arachidonate monooxygenase Journal of Lipid Research 41 2 163 81 doi 10 1016 S0022 2275 20 32049 6 PMID 10681399 Gopal V Raj Jagadeesh S G Reddy Y Krishna Bandyopadhyay A Capdevila Jorge H Falck J R 15 March 2004 A practical stereospecific route to 18 19 and 20 hydroxyeicosa 5 Z 8 Z 11 Z 14 Z tetraenoic acids 18 19 and 20 HETEs Tetrahedron Letters 45 12 2563 2565 doi 10 1016 j tetlet 2004 01 151 ISSN 0040 4039 Capdevila Jorge H Wei Shouzou Kumar Anil Kobayashi Jun Snapper James R Zeldin Darryl C Bhatt Rama K Falck John R 1 December 1992 Resolution of dihydroxyeicosanoates and of dihydroxyeicosatrienoates by chiral phase chromatography Analytical Biochemistry 207 2 236 240 doi 10 1016 0003 2697 92 90006 S ISSN 0003 2697 PMID 1481976 a b Karara A Dishman E Blair I Falck JR Capdevila JH 25 November 1989 Endogenous epoxyeicosatrienoic acids Cytochrome P 450 controlled stereoselectivity of the hepatic arachidonic acid epoxygenase The Journal of Biological Chemistry 264 33 19822 7 doi 10 1016 S0021 9258 19 47185 8 PMID 2584196 Zeldin DC Kobayashi J Falck JR Winder BS Hammock BD Snapper JR Capdevila JH 25 March 1993 Regio and enantiofacial selectivity of epoxyeicosatrienoic acid hydration by cytosolic epoxide hydrolase The Journal of Biological Chemistry 268 9 6402 7 doi 10 1016 S0021 9258 18 53266 X PMID 8454612 McGiff John C Quilley John March 2001 20 Hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids and blood pressure Current Opinion in Nephrology and Hypertension 10 2 231 237 doi 10 1097 00041552 200103000 00012 ISSN 1062 4821 PMID 11224699 S2CID 44774278 Roman RJ January 2002 P 450 metabolites of arachidonic acid in the control of cardiovascular function Physiological Reviews 82 1 131 85 doi 10 1152 physrev 00021 2001 PMID 11773611 Pfister Sandra L Gauthier Kathryn M Campbell William B 1 January 2010 Vascular Pharmacology of Epoxyeicosatrienoic Acids Chapter 2 Vascular Pharmacology of Epoxyeicosatrienoic Acids Advances in Pharmacology Vol 60 Academic Press pp 27 59 doi 10 1016 b978 0 12 385061 4 00002 7 ISBN 9780123850614 PMC 3373307 PMID 21081214 Imig John D 1 July 2013 Epoxyeicosatrienoic acids 20 hydroxyeicosatetraenoic acid and renal microvascular function Prostaglandins amp Other Lipid Mediators 104 105 2 7 doi 10 1016 j prostaglandins 2013 01 002 ISSN 1098 8823 PMC 3664103 PMID 23333581 Alonso Galicia Magdalena Falck John R Reddy Komandla Malla Roman Richard J 1 November 1999 20 HETE agonists and antagonists in the renal circulation American Journal of Physiology Renal Physiology 277 5 F790 F796 doi 10 1152 ajprenal 1999 277 5 F790 ISSN 1931 857X PMID 10564244 Falck JR Koduru SR Mohapatra S Manne R Atcha KR Atcha R Manthati VL Capdevila JH Christian S Imig JD Campbell WB 28 August 2014 14 15 Epoxyeicosa 5 8 11 trienoic Acid 14 15 EET surrogates carboxylate modifications Journal of Medicinal Chemistry 57 16 6965 72 doi 10 1021 jm500262m PMC 4148164 PMID 25119815 Campbell William B Imig John D Schmitz James M Falck John R October 2017 Orally Active Epoxyeicosatrienoic Acid Analogs Journal of Cardiovascular Pharmacology 70 4 211 224 doi 10 1097 FJC 0000000000000523 ISSN 0160 2446 PMC 5673125 PMID 28937442 Falck J R Bhatt Rama K Ye Jianhua June 1995 Tin Copper Transmetalation Cross Coupling of alpha Heteroatom Substituted Alkyltributylstannanes with Organohalides Journal of the American Chemical Society 117 22 5973 5982 doi 10 1021 ja00127a010 ISSN 0002 7863 Ye Jianhua Bhatt Rama K Falck J R 10 December 1993 Stereospecific a alkoxystannane couplings with acyl chlorides Total synthesis of goniofufurone Tetrahedron Letters 34 50 8007 8010 doi 10 1016 S0040 4039 00 61436 3 ISSN 0040 4039 Jat Jawahar L Paudyal Mahesh P Gao Hongyin Xu Qing Long Yousufuddin Muhammed Devarajan Deepa Ess Daniel H Kurti Laszlo Falck John R 3 January 2014 Direct Stereospecific Synthesis of Unprotected N H and N Me Aziridines from Olefins Science 343 6166 61 65 Bibcode 2014Sci 343 61J doi 10 1126 science 1245727 ISSN 0036 8075 PMC 4175444 PMID 24385626 Paudyal Mahesh P Adebesin Adeniyi Michael Burt Scott R Ess Daniel H Ma Zhiwei Kurti Laszlo Falck John R 9 September 2016 Dirhodium catalyzed C H arene amination using hydroxylamines Science 353 6304 1144 1147 Bibcode 2016Sci 353 1144P doi 10 1126 science aaf8713 ISSN 0036 8075 PMC 5040325 PMID 27609890 Anugu Raghunath Reddy Munnuri Sailu Falck John R 18 March 2020 Picolinate Directed Arene meta C H Amination via FeCl 3 Catalysis Journal of the American Chemical Society 142 11 5266 5271 doi 10 1021 jacs 9b13753 ISSN 0002 7863 PMID 32090542 S2CID 211262974 Falck J R Yu Jurong Cho Hyun Sung August 1994 A convenient synthesis of unsymmetric polyfluoroethers Tetrahedron Letters 35 33 5997 6000 doi 10 1016 0040 4039 94 88058 1 Anderson R G Falck J R Goldstein J L Brown M S August 1984 Visualization of acidic organelles in intact cells by electron microscopy Proceedings of the National Academy of Sciences 81 15 4838 4842 Bibcode 1984PNAS 81 4838A doi 10 1073 pnas 81 15 4838 ISSN 0027 8424 PMC 391586 PMID 6146980 Bolitt Veronique Mioskowski Charles Kollah R Ominde Manna Sukumar Rajapaksa D Falck J R July 1991 Total synthesis of vineomycinone B2 methyl ester via double Bradsher cyclization Journal of the American Chemical Society 113 16 6320 6321 doi 10 1021 ja00016a086 ISSN 0002 7863 Retrieved from https en wikipedia org w index php title John R Falck amp oldid 1167620495, wikipedia, wiki, book, books, library,

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