Spirocycles and the Development of a MDM2 antagonist
|
|
|
- Hannah Adams
- 5 years ago
- Views:
Transcription
1 Spirocycles and the Development of a MDM2 antagonist 1 Presenter: Brent Billett Advisor: Prof. Guangbin Dong University of Texas at Austin March 2, 2016
2 Outline Introduction Examples of spirocycle formation/synthesis Examples of thiazolidine formation/synthesis; a reoccurring and potent moiety Biological Aside western blot, cell cycle, and P53-MDM2 complex Specific thiazolidine drug example
3 Spirocycle Examples cyclopropanes oxiranes oxetanes spirooxindol spirooxindol-3,3 - thiazolidine spiroazetidines
4 Spirocycle features Rigidify ligand conformation upon ligation to target Conformation restriction within molecule Ligand binding entropy Greater 3-dimensionality more physical properties when compared to planar/aromatic derivatives Novelty for patentability Zheng, Y.; Tice, C. M.; Singh, S. B. Bioorg. Med. Chem. Lett. 2014, 24, 3673.
5 Spirocycle feature: constraint/rigidity 1a is twice as potent and more selective than early lead 1b due to 3 membered spiro constraint. Zheng, Y.; Tice, C. M.; Singh, S. B. Bioorg. Med. Chem. Lett. 2014, 24, 3673.
6 Synthesis of spirocycles Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540
7 NHC-catalyzed cycloaddition/annulation Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Wang, X.; Zhang, Y.; Ye, S. Adv. Synth. Catal. 2010, 352, 1892
8 NHC-Catalyzed [3+2] alcohol directed Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Sun, L. H.; Shen, L.T.; Ye, S. Chem. Commun. 2011, 47, 10136
9 Cooperative NHC/Lewis Acid Strategy Question: Please provide a stereochemical model for the observed stereochemistry in the NHC/Lewis Acid strategy case. (the conversion of benzoquinone 38 to spirolactone 47) Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Scheidt, K.A. Chem. Sci. 2012, 3, 53 and Angew. Chem. Int. Ed. 2012, 51, 4963
10 Michael Reaction Strategy complementary spirolactone formation Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Bergonzini, G.; Melchiorre, P. Angew. Chem. 2012, 51, 995
11 Zn-ProPhenol Spirolactone Synthesis Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Trost, B. M.: Hirano, K. Org. Lett. 2012, 14, 2446
12 Zn-ProPhenol Spirolactone Synthesis racemic racemic 11% ee Trost, B. M.: Hirano, K. Org. Lett. 2012, 14, 2446
13 Asymmetric [3+2] allylsilane annulation Takes advantage of the inherent enantioselectivity of allylsilanes Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Franz, A.K. Angew. Chem. Int. Ed. 2012, 51, 989
14 Pd catalyzed spirocyclic-pentanes Using achiral ligand affords 2:1 trans/cis diastereomers Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Trost, B. M.; J. Am. Chem Soc. 2007, 129, 12396
15 Wall and Flap Model Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Trost, B. M.; Angew. Chem., Int. Ed. 2011, 50, 6167
16 Trienamine/DA approach remarkably broad strategy for the enantioselective synthesis of complex spirocycles Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540
17 Trienamine/DA approach Strategy Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Jorgensen, K. A.; J. Am. Chem. Soc. 2011, 133, 5053
18 Ring Expansion Approach Franz, A. K.; Hanhan, N. V.; Ball-Jones, N.R. ACS Catal. 2013, 3, 540 Chai, Z.; Rainey, T.J. J. Am. Chem. Soc. 2012, 134, 3615
19 Proposed reaction mechanism Chai, Z.; Rainey, T.J. J. Am. Chem. Soc. 2012, 134, 3615
20 Thiazolidines Indoles and its analogous (such as isatin) are good pharmacophores for designing chemotherapeutic Spiro[indole-thiazolidines] have broad spectrum of pharmacological properties R. Sakhuja et al. Bioorg. Med. Chem. Lett. 2011, 21, 5465
21 Example synthesis of a thiazolidine racemate of one ntantiomeric pair R. Sakhuja et al. Bioorg. Med. Chem. Lett. 2011, 21, 5465
22 Another example of thiazolidine (a) NaH, DMF, 0 o C then ArCH 2 Br or Alk-X; (b) (1) Ar NH 2, EtOH, reflux, 6 h; (2) mercaptoacetic (aka thioglycolic acid) acid, toluene, reflux, 16 h; (c) mcpba (5 equiv), CHCl 3, rt, 24h (d) mcpba (1.1 equiv), CHCl 3, 0 o C, 1 h V.V. Vintonyak et al. Tetrahedron 2011, 67, 6713
23 Thiazolidine synthesis w/ sulfactant R. Jain et al. Tetrahedron Letters 2012, 53, 6236
24 Biological Aside Before specific case study I try to show the public that chemistry, biology, physics, astrophysics is life. It is not some separate subject that you have to be pulled into a corner to be taught about. -Neil degrasse Tyson 1) cell cycle 2) p53 and MDM2 3) Western Blot
25 Cell Cycle Phase Abbreviation Description Interphase I Includes G o, S, and G 1 Gap 1 G 1 cell growth, protein and organelles accumulation Synthesis S DNA replication Gap 2 G 2 Cell growth Mitosis M Cell division Gap 0 G 0 Quiescent/ senescent
26 P53-MDM2 Crystal structure of the p53-binding domain of MDM2
27 Western Blotting 1) Cell lysis and separation to extract protein 2) Gel Electrophoresis - Charged molecules are separated according to physical properties
28 Transfer Method: Blotting 3) Blotting proteins are transferred to a membrane via electroelution. Nonspecific sites of the remaining membrane surface are blocked Proteins are labeled for detection
29 Specific Case Study Development of a MDM2 antagonist 1 Inhibits 30% of p53-mdm2 interaction by mimicking p53 residues Phe19 and Trp23 that bind to MDM2 Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
30 Outline of MDM2 antagonist Discovery Structural-based design Library construction and in vitro cytotoxicity (paper 2) Library construction and in vitro cytotoxicity (paper 1) 1 2 Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
31 Synthesis of derivatives (i) Cys-OEt, NaHCO 3 in MeOH, MW; (ii) triphosgene TEA, THF, rt, 10 min, then R 2 - NH 2; (iii) MeOH, TEA, reflux, 1-3 hr Cysteine ethyl ester Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
32 Cytotoxic activity of derivatives Cell Lines: HEK, transformed human embryonic kidney cell line; M14, human melanoma cell line; U937, Human leukemia monocyte lymphoma Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
33 Cytotoxic activity of derivatives Cell Lines: HEK, transformed human embryonic kidney cell line; M14, human melanoma cell line; U937, Human leukemia monocyte lymphoma Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
34 Hit compounds 9c and 10d To undergo additional in vitro testing and derivatization Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
35 Derivatives 9c and 10d exhibit good cell selectivity a) Human papillary thyroid carcinoma TPC1 b) Normal thyroid TAD-2 cell Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
36 Derivatives of 9c and 10d acylated series less potent Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
37 Video Time Lapse Microscopy treated cells experienced reduced cell division, but what was the cause of the reduced cell division? Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
38 Determining mode of Cytotoxicity Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
39 Determining mode of Cytotoxicity Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319
40 Determining mode of Cytotoxicity Both treated cells exhibit and increase in p53 concentration Gomez-Monterrey. et al. J. Med. Chem., 2010, 53, 8319 a) p53-mdm2 complex and b) 9c c) 10d d) nutlin-3 treated
41 Further Development of 9c Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
42 Derivatization Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
43 Synthesis of Series 4 (i) Cys-OEt, NaHCO 3 in EtOH; (ii) R 2 -COCl, TEA, THF, 2 h, rt What about stereoselectivity? => lets look at a similar system Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
44 Facile Ring Opening of Spirooxindoles a look at a similar system Yujun Zhao et al. J. Am. Chem. Soc. 2013, 135, 7223 and J. Med. Chem. 2013, 56, 5553
45 Stable cis-cis isomer Open ring intermediate
46 Isomerization Mechanism a look at a similar system Yujun Zhao et al. J. Am. Chem. Soc. 2013, 135, 7223 and J. Med. Chem. 2013, 56, 5553
47 Stereochemistry Question: Please provide a mechanistic rational for the observed isomerization. Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
48 Synthesis of Series 5 (i) 4-Cl-C 6 H 4 COCl, TEA, THF, 2h, rt; (ii) Cys-OEt, NaHCO 3, EtOH Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
49 Biological effects MCF-7: Human breast adenocarcinoma cell. HT29: Human colon carcinoma cell
50 Biological effects MCF-7: Human breast adenocarcinoma cell. HT29: Human colon carcinoma cell Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
51 Hit compound 4n Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
52 Binding Model Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
53 Determination of p53 levels Total cell lysates After immunoprecipitation Western blot Quantification of immunoblots Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
54 Cell cycle progression a) 24 hr b) 48hrs c)72 hrs d) 24 hr and varying concentration Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
55 Apoptotic cell death Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
56 Mechanism of apoptosis Bertamino, A. et al. J. Med. Chem., 2013, 56, 5407
57 Summary Examples of spirocycle formation/synthesis Examples of thiazolidine formation/synthesis; a reoccurring and potent moiety Biological Aside western blot, cell cycle, and P53-MDM2 complex Specific thiazolidine drug example 4n high efficiency in breast, colon, lung, and leukemia cancer cell lines Docking studies allowed to predict bind mode 4n induces apoptosis
58 THANK YOU
59 Question 1
60 Question 2: Western Blotting 1) Cell lysis and separation to extract protein 2) Gel Electrophoresis - Charged molecules are separated according to physical properties
61 Question 2: Transfer Method: Blotting 3) Blotting proteins are transferred to a membrane via electroelution. Nonspecific sites of the remaining membrane surface are blocked Proteins are labeled for detection
62 Question 3 Base-catalyzed isomerization of thiazolidines through Schiff Base intermediates (I) is a well-known process Trost, B.M. et al. Angew. Chem. Int. Ed., 2011, 50, 6167
63 Wall and Flap Model Trost, B.M. et al. Angew. Chem. Int. Ed., 2011, 50, 6167
N-Heterocyclic Carbene Catalysis via Azolium Dienolates: An Efficient Strategy for Enantioselective Remote Functionalizations
Angew. Chem. Int. Ed. 2017, 10.1002. 1 N-Heterocyclic Carbene Catalysis via Azolium Dienolates: An Efficient Strategy for Enantioselective Remote Functionalizations Reporter: En Li Supervisor: Prof. Yong
Stereodivergent Catalysis. Aragorn Laverny SED Group Meeting July
Stereodivergent Catalysis Aragorn Laverny SED Group Meeting July 31 2018 1 Stereodivergent Catalysis In the context of asymmetric synthesis, a stereodivergent process is one that allows access to any given
Direct Oxidative Heck Cyclizations: Intramolecular Fujiwara-Moritani Arylations for the Synthesis of Functionalized Benzofurans and Dihydrobenzofurans
Direct xidative eck Cyclizations: Intramolecular Fujiwara-Moritani Arylations for the Synthesis of Functionalized Benzofurans and Dihydrobenzofurans by Zhang,.; Ferreira, E. M.; Stoltz, B. M. Angewandte
Molybdenum-Catalyzed Asymmetric Allylic Alkylation
Molybdenum-Catalyzed Asymmetric Allylic Alkylation X MoL n u u * Tommy Bui 9/14/04 Asymmetric Allylic Alkylation from a Synthetic Viewpoint X X M u u * and/or u form a C-C bond with the creation of a new
Copper-Catalyzed Synthesis of Esters from Ketones. Alkyl Group as a Leaving Group.
Copper-Catalyzed Synthesis of Esters from Ketones. Alkyl Group as a Leaving Group. akatani, Y.; Koizumi, Y.; Yamasaki, R.; Saito, S. rg. Lett. 2008, 10, 2067-2070. An Annulation Reaction for the Synthesis
Palladium-Catalyzed Asymmetric Benzylic Alkylation Reactions
Palladium-Catalyzed Asymmetric Benzylic Alkylation Reactions Reporter: Hong-Qiang Shen Checker: Cong Liu Date: 2016/07/12 Masahiro Miura et al. Angew. Chem. Int. Ed. 2016, 55, 6973. Masahiro Miura Osaka
Catalytic Asymmetric [4+1] Annulation of Sulfur Ylides with Copper Allenylidene Intermediates. Reporter: Jie Wang Checker: Shubo Hu Date: 2016/08/02
![Catalytic Asymmetric [4+1] Annulation of Sulfur Ylides with Copper Allenylidene Intermediates. Reporter: Jie Wang Checker: Shubo Hu Date: 2016/08/02](/thumbs/93/114018431.jpg "Catalytic Asymmetric [4+1] Annulation of Sulfur Ylides with Copper Allenylidene Intermediates. Reporter: Jie Wang Checker: Shubo Hu Date: 2016/08/02")
Catalytic Asymmetric [4+1] Annulation of Sulfur Ylides with Copper Allenylidene Intermediates Reporter: Jie Wang Checker: Shubo Hu Date: 2016/08/02 Xiao, W.-J. et al. J. Am. Chem. Soc. 2016, 138, 8360.
Michelangelo Gruttadauria
Michelangelo Gruttadauria Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università di Palermo, Viale delle Scienze - Edificio 17, 90128, Palermo 1 Main focus theme: Organic
I. Introduction. Peng Zhao. Liu lab
Asymmetric Total Synthesis of Mycoleptodiscin A Shupeng Zhou, Hao Chen, Yijie Luo, Wenhao Zhang and Ang Li Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai
Literature Report IX. Cho, S. H. et al. Org. Lett. 2016, 18, Cho, S. H. et al. Angew. Chem. Int. Ed. 2017, 56,
Literature Report IX ynthesis of β-aminoboronates by Copper(I)- Catalyzed Addition of Diborylalkanes to Imines Reporter Checker Date : hubo Hu : Xiaoyong Zhai : 2017-9-1818 Cho,. H. et al. rg. Lett. 2016,
Literature Report. Catalytic Enantioselective Synthesis of Isoindolinones through a Biomimetic Approach. : Zhong Yan : Ji Zhou :
Literature Report Catalytic Enantioselective Synthesis of Isoindolinones through a Biomimetic Approach Reporter Checker Date : Zhong Yan : Ji Zhou : 2017-12-22 Min, C.; Lin, Y.; Seidel, D. Angew. Chem.
Structure at the isoelectric point: The predominant form of this tripeptide at ph 1 has a net charge of: (circle one)
ame Key 21 F07-Final exam Page 2 I. (1 points) Using the pka information given on page 12, match the following isoelectric point (pi) values (3.08, 6.00, and 10.76) to their corresponding amino acids by
C H activation of aliphatic amines without unnecessary mask M2 Takaya Togo
C H activation of aliphatic amines without unnecessary mask 2017.11.25 M2 Takaya Togo 1 Outline 1.Introduction 2.Free amines as DG Discovery of new activation mode Mechanistic studies Application of the
Supporting Information
Supporting Information Enantioselective Synthesis of 3-Alkynyl-3-Hydroxyindolin-2-ones by Copper-Catalyzed Asymmetric Addition of Terminal Alkynes to Isatins Ning Xu, Da-Wei Gu, Jing Zi, Xin-Yan Wu, and
Suggested solutions for Chapter 41
s for Chapter 41 41 PBLEM 1 Explain how this synthesis of amino acids, starting with natural proline, works. Explain the stereoselectivity of each step after the first. C 2 C 2 3 CF 3 C 2 2 Pd 2 C 2 +
Scalable Total Syntheses of N-Linked Tryptamine Dimers by Direct Indole-Aniline Coupling: Psychotrimine and Kapakahines B and F
Scalable Total Syntheses of -Linked Tryptamine Dimers by Direct ndole-aniline Coupling: Psychotrimine and Kapakahines B and F tryptamine X electrophilic nitrogen source 2 methodology development innovative
Supplementary Information
Supplementary Information An engineered protein antagonist of K-Ras/B-Raf interaction Monique J. Kauke, 1,2 Michael W. Traxlmayr 1,2, Jillian A. Parker 3, Jonathan D. Kiefer 4, Ryan Knihtila 3, John McGee
Chiral Amplification. Literature Talk Fabian Schneider Konstanz, Universität Konstanz
Chiral Amplification Literature Talk Fabian Schneider Konstanz, 18.10.2017 Overview 1) Motivation 2) The nonlinear Effect in asymmetric catalysis - First encounters - Basic principles - Formalization and
Spiro Monophosphite and Monophosphoramidite Ligand Kit
Spiro Monophosphite and Monophosphoramidite Ligand Kit metals inorganics organometallics catalysts ligands custom synthesis cgm facilities nanomaterials 15-5162 15-5150 15-5156 15-5163 15-5151 15-5157
Phosphine-Catalyzed Formation of Carbon-Sulfur Bonds: Catalytic Asymmetric Synthesis of gamma-thioesters
Phosphine-Catalyzed Formation of Carbon-Sulfur Bonds: Catalytic Asymmetric Synthesis of gamma-thioesters The MIT Faculty has made this article openly available. Please share how this access benefits you.
Short Literature Presentation 10/4/2010 Erika A. Crane
Copper-Catalyzed Enantioselective Synthesis of trans-1- Alkyl-2-substituted Cyclopropanes via Tandem Conjugate Additions-Intramolecular Enolate Trapping artog, T. D.; Rudolph, A.; Macia B.; Minnaard, A.
Asymmetric Synthesis of α-substituted Allyl Boranes and Their Application in the Synthesis of Iso-agatharesinol
Asymmetric Synthesis of αsubstituted Allyl oranes and Their Application in the Synthesis of Isoagatharesinol Yuang Yu Fang and Varinder K. Aggarwal University of ristol, UK Angew. Chem. Int. Ed. 2007,
Marvin 5.4 A new generation of structure indexing at Elsevier. Dr. Michael Maier, Dr. Heike Nau, Elsevier
Marvin 5.4 A new generation of structure indexing at Elsevier Dr. Michael Maier, Dr. Heike Nau, Elsevier Agenda Elsevier: Reaxys database Compound classes Structure requirements Marvin 5.4 Decision process
Enantioselective Borylations. David Kornfilt Denmark Group Meeting Sept. 14 th 2010
Enantioselective Borylations David Kornfilt Denmark Group Meeting Sept. 14 th 2010 30.000-foot View Enantioenriched Organoboranes What to do with them Crudden C. M. et. al., Eur. J. Org. Chem. 2003, 46
Asymmetric Synthesis of Medium-Sized Rings by Intramolecular Au(I)-Catalyzed Cyclopropanation
Asymmetric Synthesis of Medium-Sized ings by Intramolecular Au(I)-Catalyzed Cyclopropanation 1 2 Iain D. G. Watson, Stefanie itter, and F. Dean Toste JACS, ASAP, 1/22/2009 DI: 10.1021/ja8085005 2.5 mol%
C H Activated Trifluoromethylation
Literature report C H Activated Trifluoromethylation Reporter:Yan Fang Superior:Prof. Yong Huang Jun. 17 th 2013 Contents Background Trifluoromethylation of sp-hybridized C-H Bonds Trifluoromethylation
A Tandem Semipinacol Rearrangement/Alkylation of a-epoxy Alcohols: An Efficient and Stereoselective Approach to Multifunctional 1,3-Diols
A Tandem Semipinacol Rearrangement/Alkylation of a-epoxy Alcohols: An Efficient and Stereoselective Approach to Multifunctional 1,3-Diols B() 2 H H B() 2 H H Hu, X.-D.; Fan, C.-A.; Zhang, F.-M.; Tu, Y.
An Efficient Total Synthesis and Absolute Configuration. Determination of Varitriol
An Efficient Total Synthesis and Absolute Configuration Determination of Varitriol Ryan T. Clemens and Michael P. Jennings * Department of Chemistry, University of Alabama, 500 Campus Dr. Tuscaloosa, AL
Synthesis of Polyfluorinated and Polychlorinated Hydrocarbons
Synthesis of Polyfluorinated and Polychlorinated Hydrocarbons Yong Guan Feb. 13, 2009 Nicoletti, M.; O Hagan, D.; Slawin, A.M.Z. J. Am. Chem. Soc. 2005, 127, 482. Hunter, L.; O Hagan, D.; Slawin, A.M.Z.
Construction of Chiral Tetrahydro-β-Carbolines: Asymmetric Pictet Spengler Reaction of Indolyl Dihydropyridines
Literature Report V Construction of Chiral Tetrahydro-β-Carbolines: Asymmetric Pictet Spengler Reaction of Indolyl Dihydropyridines Reporter Checker Date : Xiao-Yong Zhai : Xin-Wei Wang : 2018-04-02 You,
Organocatalytic Umpolung via N- Heterocyclic Carbenes. Qinghe Liu Hu Group Meeting August 20 th 2015
rganocatalytic Umpolung via N- Heterocyclic Carbenes Qinghe Liu Hu Group Meeting August 20 th 2015 Contents Part 1: Introduction Part 2: N-Heterocyclic carbene-catalyzed umpolung: classical umpolung, conjugated
Current Literature. Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of CDK8
Current Literature Development of ighly Potent and Selective Steroidal Inhibitors and Degraders of CDK8 ACS Med. Chem. Lett. 2018, ASAP Rational Drug Development simplification Cortistatin A 16-30 steps;
From Fragments to Actin: The Bistramide A Story. March 12 th, 2010
From Fragments to Actin: The Bistramide A Story March 12 th, 2010 Act I: The Protagonist Synthesis of Bistramide A Gillis, Wang, Davis, Fujii, Bromann Bistramide A Biological Activity Cell Cycle Regulation
"-Amino Acids: Function and Synthesis
"-Amino Acids: Function and Synthesis # Conformations of "-Peptides # Biological Significance # Asymmetric Synthesis Sean Brown MacMillan Group eting ovember 14, 2001 Lead eferences: Cheng,. P.; Gellman,
Asymmetric Palladium Catalyzed Cross-Coupling Reactions. Topic Talk September 4 th, 2014 Morken Lab Emma Edelstein 1
Asymmetric Palladium Catalyzed Cross-Coupling Reactions Topic Talk September 4 th, 2014 Morken Lab Emma Edelstein 1 Palladium Catalyzed Cross-Coupling Reactions 2 Kumada/Negishi Cross-Coupling Kumada:
Total Synthesis of (+/-)-Goniomitine via a Formal Nitrile/Donor-Acceptor Cyclopropane [3 + 2] Cyclization
![Total Synthesis of (+/-)-Goniomitine via a Formal Nitrile/Donor-Acceptor Cyclopropane [3 + 2] Cyclization](/thumbs/82/85235286.jpg "Total Synthesis of (+/-)-Goniomitine via a Formal Nitrile/Donor-Acceptor Cyclopropane [3 + 2] Cyclization")
Total Synthesis of (+/-)-Goniomitine via a Formal itrile/donor-acceptor Cyclopropane [3 + 2] Cyclization (-)-Goniomitine Christian L. Morales and Brian Pagenkopf* rganic Letters, ASAP Current Literature
Midterm Exam #1 /280 CHEM 6352 Fall 2011
Midterm Exam #1 /280 CEM 6352 Fall 2011 ( %) Name Sept 30 th, 2011 18:00-21:00 You may NT use any references or aids to complete the following with the exception of a chemical model set and the scrap paper
Organic Cumulative Exam February 22, 2018
rganic Cumulative Exam February 22, 2018 Answer only three of the five questions. o more than three question answers will be graded and any work not to be considered must be clearly marked as such. early
Palladium-catalyzed sp 3 C H activation. Yan Xu Dong Group Meeting Apr. 2, 2014
Palladium-catalyzed sp 3 C H activation, Yan Xu Dong Group Meeting Apr. 2, 2014 Content 1 Allylic C H activation 2 Benzylic C H activation Palladiumcatalyzed sp 3 C H activation 3 4 Common sp 3 C H activation:
Self-stable Electrophilic Reagents for Trifluoromethylthiolation. Reporter: Linrui Zhang Supervisor: Prof. Yong Huang Date:
Self-stable Electrophilic Reagents for Trifluoromethylthiolation Reporter: Linrui Zhang Supervisor: Prof. Yong Huang Date: 2017-12-25 Content Introduction Trifluoromethanesulfenates: Preparation and reactivity
Stereoselective Synthesis of Configurationally Stable Functionalized Ethano-Bridged Tröger Bases
Stereoselective Synthesis of Configurationally Stable Functionalized Ethano-Bridged Tröger Bases Michon, C.; Sharma, A.; Bernardinelli, G.; Francotte, E.; Lacour, J. Chem. Commun., 2010, 46, 2206-2208
Name: CHEM 633: Advanced Organic Chemistry: Physical Final Exam. Please answer the following questions clearly and concisely.
Name: 1 CEM 633: Advanced rganic Chemistry: Physical Final Exam Please answer the following questions clearly and concisely. You may write your answers in the space provided and/or on additional pages.
Highly Efficient, Convergent, and Enantioselective Synthesis of Phthioceranic Acid
Highly Efficient, Convergent, and Enantioselective Synthesis of Phthioceranic Acid Shiqing Xu, Akimichi Oda, Thomas Bobinski, Haijun Li, Yohei Matsueda, and Ei-ichi Negishi Angew. Chem. Int. Ed. 2015,
Aziridine Carboxylates, Carboxamides and Lactones: New Methods for Their Preparation and Their Transformation into α- and β-amino Acid Derivatives
Molecules 2000, 5 293 Aziridine Carboxylates, Carboxamides and Lactones: ew Methods for Their Preparation and Their Transformation into α- and β-amino Acid Derivatives obert H. Dodd Institut de Chimie
The aza-baylis-hillman Reaction: Mechanism, Asymmetric Catalysis, & Abnormal Adducts. Larry Wolf SED Group Meeting
The aza-baylis-hillman Reaction: Mechanism, Asymmetric Catalysis, & Abnormal Adducts Larry Wolf SED Group Meeting 04-10-07 Outline Brief historical account and Utility Mechanism Different methods for asymmetric
Electrophilic Carbenes
Electrophilic Carbenes The reaction of so-called stabilized diazo compounds with late transition metals produces a metal carbene intermediate that is electrophilic. The most common catalysts are Cu(I)
Rising Novel Organic Synthesis
Literature report Rising Novel Organic Synthesis Methods Based on the Cleavage of N-N and N-O Bonds Reporter: Zhang-Pei Chen Checker : Mu-Wang Chen Date: 04/03/2014 Kürti, L. et al. Kürti, L. et al. Science
Moorpark College Chemistry 11 Fall Instructor: Professor Gopal. Examination #3: Section Three November 7, 2011.
Moorpark College Chemistry 11 all 2011 Instructor: Professor Gopal Examination #3: Section Three ovember 7, 2011 ame: (print) alkene < alkyne < amine < alcohol < ketone < aldehyde < amide < ester < carboxylic
Manganese-Catalyzed Late- Stage Aliphatic C H Azidation
Wipf group current literature Manganese-Catalyzed Late- Stage Aliphatic C H Azidation J. Am. Chem. Soc. 2015, 137, 5300 5303 Xiongyi Huang, Tova M. Bergsten, and John T. Groves Department of Chemistry,
Computational chemical biology to address non-traditional drug targets. John Karanicolas
Computational chemical biology to address non-traditional drug targets John Karanicolas Our computational toolbox Structure-based approaches Ligand-based approaches Detailed MD simulations 2D fingerprints
Lecture 8: September 13, 2012
CHM 223 Organic Chemistry I Fall 2012, Des Plaines Prof. Chad Landrie Lecture 8: September 13, 2012 Skillbuilder 2 Ch. 5: Stereochemistry (Sec8ons 5.1-5.5) CHM 223 Organic Chemistry I Fall 2012, Des Plaines
HO C. Explain briefly (in one or two short sentences) the meaning of the following basic stereochemical terms.
Chem 232 D. J. Wardrop wardropd@uic.edu Problem et 3 Answers Question 1. Four compounds, each having the molecular formula C 3 5, have the I spectra summarized below. What are their structures? a. ne sharp
Rhodium-Catalyzed Enantioselective
Rhodium-Catalyzed Enantioselective Isomerization of Oxabicycles Reporter: Jie Wang Checker: Shubo Hu Date: 2017-07-03 Yen, A.; Choo, K.-L.; Yazdi, S. K.; Franke, P. T.; Webster, R.; Franzoni, I.; Loh,
Use of the non-aldol aldol process in the synthesis of the C1 C11 fragment of the tedanolides: use of lactol ethers in place of tetrahydrofurans
Pergamon Tetrahedron Letters 41 (2000) 9719 9723 TETRAHEDRON LETTERS Use of the non-aldol aldol process in the synthesis of the C1 C11 fragment of the tedanolides: use of lactol ethers in place of tetrahydrofurans
Catellani Reaction (Pd-Catalyzed Sequential Reaction) Todd Luo
Catellani Reaction (Pd-Catalyzed Sequential Reaction) Todd Luo 2014.1.6 1 Content Introduction Progress of Catellani Reaction o-alkylation and Applications o-arylation and Applications Conclusion and Outlook
Enantioselective Protonations
Enantioselective Protonations Marc Timo Gieseler 25.02.2013 15.03.2013 Group Seminar AK Kalesse 1 verview Introduction Enantioselective Protonation of Cyclic Substrates Enantioselective Protonation of
I. (42 points) (a) Label the indicated sites (circles and oval box) with the appropriate stereochemical designation.
I. ( points) ame Page A. etamethasone is a powerful anti-inflammatory drug that comes with unfortunate immunosupressive properties. It is often prescribed as a topical cream that can be used to alleviate
Introduction to Chemoinformatics and Drug Discovery
Introduction to Chemoinformatics and Drug Discovery Irene Kouskoumvekaki Associate Professor February 15 th, 2013 The Chemical Space There are atoms and space. Everything else is opinion. Democritus (ca.
Note: You must have your answers written in pen if you want a regrade!!!!
NAME (Print): SIGNATURE: hemistry 310M/318M Dr. Brent Iverson 2nd Midterm November 1, 2007 Please print the first three letters of your last name in the three boxes Please Note: This test may be a bit
Literature Report I. Total Synthesis of (+)-Piperarborenine B. Reporter: Zheng Gu. Date:
Literature Report I Total Synthesis of (+)-Piperarborenine B Reporter: Zheng Gu Checker: Bo Song Date: 2016-12-12 Hu, J. L.; Xie, Z. W.; Tang, Y. J. Am. Chem. Soc. 2016, 138, 13151. Panish, R. A.; Chintala,
PhD research with Prof. Lutz H. Gade at the Univ. of Strasbourg. Postdoc in 2003 with Andreas Pfaltz (Basel Switzerland)
idium-catalyzed Asymmetric Isomerization of rimary Allylic Alcohols Mantilli, L., Gerard, D., Torche, S., Besnard, C., Mazet * C. Angew. Chem. Int. Ed., 2009, 48, 1-6 1,n-Glycols as Dialdehyde Equivalents
Chem 112A: Final Exam
Chem 112A: Final Exam December 15th, 2010 Please provide all answers in the spaces provided. You are not allowed to use a calculator for this exam, but you may use molecular model kits. nly cyclohexane
Chiral Ionic Liquids (CILs) in Asymmetric Synthesis: The story so far.
Chiral Ionic Liquids (CILs) in Asymmetric Synthesis: The story so far. Literature Presentation Aman Desai 06.16.06 1. Angew. Chem. Int. Ed. 2006, 45, 3689 2. Angew. Chem. Int. Ed. 2006, 45, 3093 3. Tetrahedron:
Asymmetric Copper-Catalyzed Synthesis of α-amino Boronate Esters from N-tert- Butanesulfinyl Aldimines
Asymmetric Copper-Catalyzed Synthesis of α-amino Boronate Esters from -tert- Butanesulfinyl Aldimines R BR 2 J. Am. Chem. Soc. 2008, 130, 6910. Melissa A. Beenen, Chihul An, and Jonathan A. Ellman rrent
The Final Learning Experience
Chemistry 212 Fall Semester 1996 The Final Learning Experience University of Missouri Columbia, Prof. Rainer Glaser Monday, December 9, 1996, 103 Schlundt all, 12:40-2:30 Your Name: Max. Question 1 (Sugars)
Topics in the November 2007 Exam Paper for CHEM1904
November 2007 Topics in the November 2007 Exam Paper for CEM1904 Click on the links for resources on each topic. 2007-N-2: 2007-N-3: 2007-N-4: 2007-N-5: 2007-N-6: 2007-N-7: Solubility Equilibrium Intermolecular
Loudon Chapter 7 Review: Cyclic Compounds Jacquie Richardson, CU Boulder Last updated 8/24/2017
Compounds with a single ring are monocyclic. For example: Assuming they have no double or triple bonds, they each have one degree of unsaturation. This means that their formulas follow the pattern C nh
Problem Points Score GSI I 30 II 21 III 28 IV 30 V 31 Total 140
hemistry 0 First ame Third Examination Last ame.5 h; 0 points please print clearly Dr. Kathleen olta ignature UM ID # PRIT TE FIRT LETTER F YUR LAT AME ERE: Problem Points core GI I 0 II III 8 IV 0 V Total
Supporting Information
Supporting Information Wiley-VCH 2008 69451 Weinheim, Germany Supporting Information for Chiral Brönsted Acid Catalyzed Asymmetric Baeyer-Villiger Reaction of 3-Substituted Cyclobutanones Using Aqueous
Partial Periodic Table
Easily Legible Printed Name: CHEM 3351 (100), Fall 2016 Professor Walba Second Hour Exam October 18, 2016 CU Honor Code Pledge: On my honor, as a University of Colorado at Boulder Student, I have neither
Rh(III)-catalyzed C-H Activation and Annulation via Oxidizing Directing Group. Lei Zhang 03/23/2016 Dong Group
Rh(III)-catalyzed C-H Activation and Annulation via Oxidizing Directing Group Lei Zhang 03/23/2016 Dong Group Content 1 Alkyne involved Annulation in Hua group 2 3 4 Brief Introduction of Internal Oxidants
Journal Club Presentation by Remond Moningka 04/17/2006
β-alkyl-α-allylation of Michael Acceptors through the Palladium-Catalyzed Three-Component Coupling between Allylic Substrate, Trialkylboranes, and Activated lefins Yoshinori Yamamoto, et al. J. rg. Chem.
Ring-Opening / Fragmentation of Dihydropyrones for the Synthesis of Homopropargyl Alcohols
Ring-pening / Fragmentation of Dihydropyrones for the Synthesis of Homopropargyl Alcohols Jumreang Tummatorn, and Gregory B. Dudley, * Department of Chemistry and Biochemistry, Florida State University,
Answer the following questions 1. Define the following : [ ( 6x2) + ( 2x4)= 20 mark]
![Answer the following questions 1. Define the following : [ ( 6x2) + ( 2x4)= 20 mark]](/thumbs/89/97487476.jpg "Answer the following questions 1. Define the following : [ ( 6x2) + ( 2x4)= 20 mark]")
Benha University Time : 2 hrs. Faculty of Science 1 st Term (2014/2015) Chemistry Department Date : 1 /1/2015 (Jun.2014) Organic photo and Stereochemistry Final Exam. ( 415 Ch.) ; for 4 th level Answer
Organic Synthesis III 8 x 1hr Lectures: Michaelmas Term Weeks 5-8 Tues; Thrs at 10am Dyson Perrins lecture theatre
Organic Synthesis III 8 x 1hr Lectures: Michaelmas Term Weeks 5-8 Tues; Thrs at 10am Dyson Perrins lecture theatre Copies of this handout will be available at http://donohoe.chem.ox.ac.uk/page16/index.html
Literature Report III
Literature Report III Regioselective ydroarylation of Alkynes Reporter: Zheng Gu Checker: Cong Liu Date: 2017-08-28 Cruz, F. A.; Zhu, Y.; Tercenio, Q. D.; Shen, Z.; Dong, V. M. J. Am. Chem. Soc. 2017,
1. Provide the common name for each of the following structures. (9 points)
I. Nomenclature: Page 1 of 9 1. Provide the common name for each of the following structures. (9 points) 2. Using IUPAC rules, correctly name each structure below. Indicate correct stereochemistry where
Solvias (R)-MeO-BIPHEP Ligand Kit
metals inorganics organometallics catalysts ligands custom synthesis cgm facilities nanomaterials Catalog # 96-3655 Solvias ()- and (S)-Me BIE Ligand Kits for asymmetric hydrogenation and other catalytic
Opioid ligands with mixed properties from substituted enantiomeric N-phenethyl-5-
Supplementary Information for: Opioid ligands with mixed properties from substituted enantiomeric N-phenethyl-5- phenylmorphans. Synthesis of a μ-agonist δ antagonist and δ-inverse agonists Kejun Cheng,
Initials: 1. Chem 633: Advanced Organic Chemistry 2011 Final Exam
Initials: 1 ame: Chem 633: Advanced rganic Chemistry 2011 Final Exam Please answer the following questions clearly and concisely. In general, use pictures and less than 10 words in your answers. Write
Chiral Supramolecular Catalyst for Asymmetric Reaction
Chiral Supramolecular Catalyst for Asymmetric Reaction 2017/1/21 (Sat.) Literature Seminar Taiki Fujita (B4) 1 Introduction Rational design of chiral ligands remains very difficult. Conventional chiral
Fall Organic Chemistry Experiment #6 Fractional Crystallization (Resolution of Enantiomers)
Suggested Reading: Fall Organic Chemistry Experiment #6 Fractional Crystallization (Resolution of Enantiomers) Jones Section 4.9 Physical Properties of Diastereomers: Optical Resolution pages 176-178 Introduction
Development of Chiral Phosphine Olefin Ligands and Their Use in Asymmetric Catalysis
Development of Chiral osphine lefin Ligands and Their Use in Asymmetric Catalysis 2 Wei-Liang Duan July 31, 2007 Research Works in Hayashi Group, Kyoto University (ct, 2003 Mar, 2007) Conventional Chiral
New insights into the mechanism of molybdenum-catalyzed asymmetric alkylation*
Pure Appl. Chem., Vol. 76, No. 3, pp. 625 633, 2004. 2004 IUPAC New insights into the mechanism of molybdenum-catalyzed asymmetric alkylation* Shane W. Krska 1,, David L. Hughes 1, Robert A. Reamer 1,
Construction of C-C or C-N Bond via C-H Activation ~Chemistry of Yong-Qiang Tu~
Literature Seminar 2010.5.26 Yao u(2) Construction of C-C or C-N Bond via C-H Activation ~Chemistry of Yong-Qiang Tu~ Contents: 1. Yong-Qiang Tu's Profile 2.LatestWorkofProfessorTu 2-1. C-H Activation
Calculate a rate given a species concentration change.
Kinetics Define a rate for a given process. Change in concentration of a reagent with time. A rate is always positive, and is usually referred to with only magnitude (i.e. no sign) Reaction rates can be
Measuring enzyme (enantio)selectivity
Measuring enzyme (enantio)selectivity Types of selectivity - review stereoisomers Stereoselective synthesis (create) vs. resolutions (separate) Enantioselectivity & enantiomeric purity Ways to measure
Reporter: Yue Ji. Date: 2016/12/26
Literature Report (11) Total Synthesis of Rubriflordilactone B Reporter: Yue Ji Checker: Mu-Wang Chen Date: 2016/12/26 Yang, P.; Yao, M.; Li, J.; Li, Y.; Li, A.* Angew. Chem. Int. Ed. 2016, 55, 6964. Laboratory
I. Introduction. II. Retrosynthetic Analysis. Andrew Baggett. Liu lab
Total Synthesis of Limonin Shuji Yamashita,* Akito Naruko, Yuki Nakazawa, Le Zhao, Yujiro Hayashi, Masahiro Hirama Tohoku University, Department of Chemistry, Aramaki-aza aoba, Aoba-ku, Sendai 980-8578
Asymmetric Nucleophilic Catalysis
Asymmetric ucleophilic Catalysis Chiral catalyst X 2 Chiral catalyst X = alkyl, X 1 2 1 Vedejs, E.; Daugulis,. J. Am. Chem. Soc. 2003, 125, 4166-4173 Shaw, S. A.; Aleman,.; Vedejs, E. J. Am. Chem. Soc.
MULTICOMPONENT REACTIONS AND ORGANOCATALYSIS: A SUITABLE COMBINATION FOR STEREOSELECTIVE SYNTHESIS OF HIGHLY SUBSTITUTED BENZAZEPINES
MULTICMPET REACTIS AD RGACATALYSIS: A SUITABLE CMBIATI FR STERESELECTIVE SYTHESIS F HIGHLY SUBSTITUTED BEZAZEPIES Martina Spallarossa Department of Chemistry and Industrial Chemistry, University of Genoa
SUPPORTING INFORMATION
Eur. J. Org. Chem. 2004 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2004 ISSN 1434 193X SUPPORTING INFORMATION Title: The (Schiff base)vanadium(v) Complex Catalyzed Oxidation of Bromide A New Method
Catalytic Asymmetric Acyl Halide-Aldehyde Cyclocondensation Reactions of Substituted Ketenes
Catalytic Asymmetric Acyl Halide-Aldehyde Cyclocondensation eactions of Substituted Ketenes Scott G. elson, Cheng Zhu, and Xiaoqiang Shen J. Am. Chem Soc. 2004, 126, 14-15. Michael C. Myers, Literature
Chem 253 Problem Set 7 Due: Friday, December 3, 2004
Chem 253 roblem Set 7 ue: Friday, ecember 3, 2004 Name TF. Starting with the provided starting material, provide a concise synthesis of. You may use any other reagents for your synthesis. It can be assumed
Massachusetts Institute of Technology. Chemistry 5.43 February 28 th, Exam #1. Question 1a /4 points Question 2b /10 points
Massachusetts Institute of Technology Chemistry 5.43 February 28 th, 2007 Professor M. Movassaghi Exam #1 Question 1a /4 points Question 2b /10 points Question 1b /2 points Question 2c /6 points Question
Design and Synthesis of Novel Bicalutamide and Enzalutamide Deriva:ves as An:prolifera:ve Agents for the Treatment of Prostate Cancer.
Design and Synthesis of ovel Bicalutamide and Enzalutamide Deriva:ves as An:prolifera:ve Agents for the Treatment of Prostate Cancer. BasseAo, M., Ferla, S., Pertusa:, F., Kandil, S., Westwall, A. D.,
The Synthesis of Molecules Containing Quaternary Stereogenic Centers via the Intramolecular Asymmetric Heck Reaction
The Synthesis of Molecules Containing Quaternary Stereogenic Centers via the Intramolecular Asymmetric Heck Reaction Reported by Eric P. Gillis April 19, 2007 INTRODUCTION The enantioselective synthesis
Chem 232. Problem Set 9. Question 1. D. J. Wardrop
Chem 232 D. J. Wardrop wardropd@uic.edu Problem Set 9 Question 1. a. Rank in order of increasing number of chirality centers (1 = fewest chirality centers; 5 = most chirality). 3 C C 3 b. Rank in order
May CUME. Department of Chemistry University of Missouri Columbia Saturday, May 10, O Clock Chemistry Reading Room. Dr.
May CUME Department of Chemistry University of Missouri Columbia Saturday, May 10, 1997 @Nine O Clock Chemistry Reading Room Dr. Rainer Glaser Announced Reading The Chemistry of Amir Hoveyda, Boston College,
Synthesis of 3-halo-2,5-disubstituted furans via CuX mediated cyclization-halogenation reactions
University of Wollongong Research Online Faculty of Science - Papers (Archive) Faculty of Science, Medicine and Health 2011 Synthesis of 3-halo-2,5-disubstituted furans via CuX mediated cyclization-halogenation