1 Ph.D. University of Rochester, 1987 - Robert K. Boeckman Jr. Part I.  -Lithio Vinyl Ether Anion Chemistry Part II. Synthesis of X-14547A (Indanomycin)

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2 1 Ph.D. University of Rochester, 1987 - Robert K. Boeckman Jr. Part I.  -Lithio Vinyl Ether Anion Chemistry Part II. Synthesis of X-14547A (Indanomycin) Subunit Part III. Total Synthesis of A-23187 (Calcimycin) PDF - Harvard, David A. Evans Part IV. Synthesis of Bryostatin Subunit André B. Charette Group Meeting September 26, 2005

3 2 Background Début du BSc. Septembre 1980 Travail été 1981 - Chimie analytique - Joseph Hubert Travail été 1982 - Chimie “bio-organique” - Hermann Dugas Automne 1982 - Décision de prendre la direction du sud pour les études graduées… B.Sc. Université de Montréal Mai 1983 Début à Rochester Septembre 1983 - cours, démo, choix du boss, cumes Début de la recherche en Janvier 1984 Début de la rédaction en Juillet 1987 Soutenance: 28 septembre 1987 Début du postdoc: 15 octobre 1987 Fin du postdoc: 30 juin 1989…pour affronter l’Université Laval et la belle vie de prof à 27 ans…

4 3  -Lithio Vinylether anions

5 4 Synthesis of Organolithium Compounds

6 5 O-Phosphorylation of Lactones

7 6 Synthesis of Vinyl Sulfides

8 7 Reductive Lithiation of Cyclic Ketene Monothioacetals

9 8

10 9 Other Possible Precursors Based on Radical Stability

11 10 The X-14547A Problem

12 11 The X-14547A Problem: Cohen’s Chemistry

13 12 The X-14547A Problem

14 13 The X-14547A Problem: Model Study

15 14 The X-14574A Problem: Synthesis of the Tetrahydropyran Subunit

16 15 The X-14547A Problem: Mass Spectrometry Studies

17 16 The X-14547A Problem: Protecting Group Issue

18 17 The X-14547A Left Subnit Assemblage

19 18 Retrosynthetic Analysis

20 19 Synthesis of the Aryl Subunit

21 20 Synthesis of the Aryl Subunit

22 21 Synthesis of the Vinyl Ether Precursor

23 22 Synthesis of the Vinyl Ether Precursor

24 23 Synthesis of the Electrophile

25 24 Coupling of the Fragments

26 25 Incorporation of the Acyl Pyrrole

27 26 Final Dehydration and Deprotection

28 27 Synthesis of the C-Ring of Bryostatin

29 28 Aryl-subtituted Epoxyalcohols as 1,3-Polyol Equivalents

30 29 Retrosynthetic Analysis

31 30 Retrosynthetic Analysis of the C-Ring

32 31 Elaboration of the Synthetic Methodology

33 32 Optimization of the Birch Reduction/Ozonolysis Reactions

34 33 Key Chemoselective Protection

35 34 Synthesis of the Dihydropyran

36 35 Functionalization of the Dihydropyran

37 36 Attempts at Improving the Diastereomeric Ratio

38 37 Synthesis of the Other Diastereomer

39 38 Incorporation of the ,  -Unsaturated Ester Unit

40 39 Playing with the Oxidation State

41 40 Test for the Julia Olefination Reaction

42 41 Regeneration of the Methyl Ester…