Presentation is loading. Please wait.

Presentation is loading. Please wait.

Total Synthesis of BE-43472B. PhD Work with Prof. André B. Charette.

Published bySamira Lumb Modified over 10 years ago

Similar presentations

Presentation on theme: "Total Synthesis of BE-43472B. PhD Work with Prof. André B. Charette."— Presentation transcript:

1 Total Synthesis of BE-43472B

2 PhD Work with Prof. André B. Charette

3 The Scripps Research Institute La Jolla, California

4 The Scripps Research Institute World's largest, private non-profit biomedical research facility Founded in 1961 by Frank Dixon, M.D. 289 Faculty members 815 Postdoctoral fellows 235 Graduate students 1,500 technical and administrative support personnel

5 The Scripps Research Institute K. C. Nicolaou - Chairman of chemistry dept. Barry K. Sharpless - Nobel laureate Phil S. Baran Dale Boger Carlos F. Barbas III Jin-Quan Yu Albert Eschenmoser Kim D. Jenda Richard Lerner Peter Schultz Julius Rebek Jr. Director, Skaggs Institute for Chemical Biology

6 BE-43472B Organism inhibited IC 50,  M MRSA, ATCC 43300 Methicilin-resistant Straphylococcus aureus 0.15 VRE, ATCC 51299 Vancomycin resistant Enterococcus faecalis 2.0 HCT-116 Human cancer cells 3.3 New structural class among known antimicrobial agents Isolated from marine streptomycete collected in Puerto Rico Chrysophanol dimer linked in tetrahydrofuran rings with an incorporated acetaldehyde molecule Socha, A. M.; Rowley D. C. et al. J. Nat. Prod. 2006, 69, 1070.

7 BE-43472B Retrosynthesis

8 Model Studies

9

10 Chrysophanol Derivative Synthesis

11 Hauser annulation

12 Chiral Diene Synthesis and Diels-Alder Reaction

13 E-Reduction of Propargylic Alcohol 1 st report by Corey in 1967 (LiAlH 4 + 2 MeOH) Red-Al introduced 15 years later by Denmark

14 Chiral Diene Synthesis and Diels-Alder Reaction

15 Ether 1,4-Elimination

16 Chiral Diene Synthesis and Diels-Alder Reaction

17 Quinone Acceptor Synthesis – Initial Hopes

18

19

20 Quinone Michael Acceptor Synthesis

21

22 hydrolysis happened in purification

23 Quinone Michael Acceptor Synthesis hydrolysis happened in purification

24 Quinone Michael Acceptor Synthesis hydrolysis happened in purification

25 Quinone Michael Acceptor Synthesis

26 Fragments Coupling and Aromatization

27 Fragments Coupling Attempts From model studies Real system

28 Fragments Coupling and Aromatization

29

30 1,4-Addition Attempts caused by in situ reducing metal?

31 1,4-Addition Attempts

32 Friedel-Crafts Fragments Coupling Attempts

33 New Strategy

34 Reversal of the Diene Electronics

35 Diene Synthesis

36 Diels-Alder with New Diene

37

38 Completion of the Synthesis

39 Photochemical Epoxide Rearrangement Nicolaou, K. C.; Lim, Y.-H.; Becker, J.; Lemire, A.; Neubauer, T.; Montero, A. J. Am. Chem. Soc. 2009, 131, 14812.

40 Acknowledgments Prof. K. C. Nicolaou Research group members Yee-Hwee Lim Jochen Becker

Download ppt "Total Synthesis of BE-43472B. PhD Work with Prof. André B. Charette."

Similar presentations

By William Schulz Bechara Charette/Collins Literature Meeting November 13 th, 2012.

By William Schulz Bechara Charette/Collins Literature Meeting November 13 th, 2012.
Prepared by : Malak Eshtayah

Prepared by : Malak Eshtayah
Amphidinolide A Isolation: 1. Kobayashi, J. et al. Tetrahedron Lett. 1986, 27, 5755. 2. Kobayashi, J. et al. J. Nat. Prod. 1991, 54, 1435. Biological Activity:

Amphidinolide A Isolation: 1. Kobayashi, J. et al. Tetrahedron Lett. 1986, 27, Kobayashi, J. et al. J. Nat. Prod. 1991, 54, Biological Activity:
Synthesis of Vancomycin from the Aglycon Christopher Thompson, Min Ge, Daniel Kahne J. Am. Chem. Soc. 1999, 121, 1237-1244 Presented by James Melnyk.

Synthesis of Vancomycin from the Aglycon Christopher Thompson, Min Ge, Daniel Kahne J. Am. Chem. Soc. 1999, 121, Presented by James Melnyk.
Enantioselective Synthesis of Pactamycin, a Complex Antitumor Antibiotic Doug Kenny 05-06-14 Science, 12 April 2013.

Enantioselective Synthesis of Pactamycin, a Complex Antitumor Antibiotic Doug Kenny Science, 12 April 2013.
Heterocyclic Chemistry

Heterocyclic Chemistry
Total Synthesis and Evaluation of [ψ[CH 2 NH]Tpg 4 ] Vancomycin Aglycon: Reengineering Vancomycin for Dual D -Ala- D - Ala and D -Ala- D -Lac Binding Brendan.

Total Synthesis and Evaluation of [ψ[CH 2 NH]Tpg 4 ] Vancomycin Aglycon: Reengineering Vancomycin for Dual D -Ala- D - Ala and D -Ala- D -Lac Binding Brendan.
D, I- and meso-Isochrysohermidin: Total Synthesis and Interstrand DNA Cross-Linking Dale L. Boger and Carmen M. Baldino JACS (1993) 115, 11418-11425 1.

D, I- and meso-Isochrysohermidin: Total Synthesis and Interstrand DNA Cross-Linking Dale L. Boger and Carmen M. Baldino JACS (1993) 115,
MICROSCOPIC KINETIC MODEL EXHIBITING CHIRAL SYMMETRY BREAKING Harold W. Hatch, Pablo G. Debenedetti Chemical Engineering Dept., Princeton Frank H. Stillinger.

MICROSCOPIC KINETIC MODEL EXHIBITING CHIRAL SYMMETRY BREAKING Harold W. Hatch, Pablo G. Debenedetti Chemical Engineering Dept., Princeton Frank H. Stillinger.
Year 3 CH3E4 notes: Asymmetric Catalysis, Prof Martin Wills

Year 3 CH3E4 notes: Asymmetric Catalysis, Prof Martin Wills
Second Semester Organic Chemistry Options: Bioorganic or Organic Mechanism and Synthesis Albert Matlin and Jason Belitsky Department of Chemistry and Biochemistry.

Second Semester Organic Chemistry Options: Bioorganic or Organic Mechanism and Synthesis Albert Matlin and Jason Belitsky Department of Chemistry and Biochemistry.
Greg Lackner Marian High School December 14 th, 2011 Chemistry After Marian: What’s out there?

Greg Lackner Marian High School December 14 th, 2011 Chemistry After Marian: What’s out there?
INTRODUCTION Based on: S. Warren Organic Synthesis: The Disconnection Approach, Wiley: New York, 1982 Chemists synthesize compounds in just about every.

INTRODUCTION Based on: S. Warren Organic Synthesis: The Disconnection Approach, Wiley: New York, 1982 Chemists synthesize compounds in just about every.
Organic Synthesis A synthesis is a specific sequence of chemical reactions that converts starting materials into the desired compound, called the target.

Organic Synthesis A synthesis is a specific sequence of chemical reactions that converts starting materials into the desired compound, called the target.
Department of Chemistry Seminar Announcement Date/Time/VenueTitle/Speaker 21 Feb (Mon) 4pm – S8 Level 3 Executive Classroom Natural products and.

Department of Chemistry Seminar Announcement Date/Time/VenueTitle/Speaker 21 Feb (Mon) 4pm – S8 Level 3 Executive Classroom Natural products and.
Olefin Metathesis and Use in Tandem Reactions - The Work of Marc L. Snapper James Mousseau Literature Meeting 6 May 2008 1.

Olefin Metathesis and Use in Tandem Reactions - The Work of Marc L. Snapper James Mousseau Literature Meeting 6 May
Click Chemistry : A ‘Click’ away from discovery. David Marcoux Charette’s Laboratories February 6 th.

Click Chemistry : A ‘Click’ away from discovery. David Marcoux Charette’s Laboratories February 6 th.
Recent Publications and Presentations: 1. Brown, T; et al.; 2006, Bioorg. Med. Chem., in preparation. 2. Buchmueller, K.L.; et al.; 2006, Biochem, in preparation.

Recent Publications and Presentations: 1. Brown, T; et al.; 2006, Bioorg. Med. Chem., in preparation. 2. Buchmueller, K.L.; et al.; 2006, Biochem, in preparation.
1 BE 10988 : An Inhibitor of DNA –Topoisomerase II Indira Thapa November 24, 2005.

1 BE : An Inhibitor of DNA –Topoisomerase II Indira Thapa November 24, 2005.
Enantioselective Total Syntheses of Manzamine A and Related Alkaloids John M. Humphrey, Yusheng Liao, Amjad Ali, Tobias Rein, Yue-Ling Wong, Hui-Ju Chen,

Enantioselective Total Syntheses of Manzamine A and Related Alkaloids John M. Humphrey, Yusheng Liao, Amjad Ali, Tobias Rein, Yue-Ling Wong, Hui-Ju Chen,

Similar presentations

Ads by Google