1 Ph.D. University of Rochester, 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 (Calcimycin) PDF - Harvard, David A. Evans Part IV. Synthesis of Bryostatin Subunit André B. Charette Group Meeting September 26, 2005

2 Background Début du BSc. Septembre 1980 Travail été Chimie analytique - Joseph Hubert Travail été Chimie “bio-organique” - Hermann Dugas Automne Décision de prendre la direction du sud pour les études graduées… B.Sc. Université de Montréal Mai 1983 Début à Rochester Septembre 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…

3  -Lithio Vinylether anions

4 Synthesis of Organolithium Compounds

5 O-Phosphorylation of Lactones

6 Synthesis of Vinyl Sulfides

7 Reductive Lithiation of Cyclic Ketene Monothioacetals

8

9 Other Possible Precursors Based on Radical Stability

10 The X-14547A Problem

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

12 The X-14547A Problem

13 The X-14547A Problem: Model Study

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

15 The X-14547A Problem: Mass Spectrometry Studies

16 The X-14547A Problem: Protecting Group Issue

17 The X-14547A Left Subnit Assemblage

18 Retrosynthetic Analysis

19 Synthesis of the Aryl Subunit

20 Synthesis of the Aryl Subunit

21 Synthesis of the Vinyl Ether Precursor

22 Synthesis of the Vinyl Ether Precursor

23 Synthesis of the Electrophile

24 Coupling of the Fragments

25 Incorporation of the Acyl Pyrrole

26 Final Dehydration and Deprotection

27 Synthesis of the C-Ring of Bryostatin

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

29 Retrosynthetic Analysis

30 Retrosynthetic Analysis of the C-Ring

31 Elaboration of the Synthetic Methodology

32 Optimization of the Birch Reduction/Ozonolysis Reactions

33 Key Chemoselective Protection

34 Synthesis of the Dihydropyran

35 Functionalization of the Dihydropyran

36 Attempts at Improving the Diastereomeric Ratio

37 Synthesis of the Other Diastereomer

38 Incorporation of the ,  -Unsaturated Ester Unit

39 Playing with the Oxidation State

40 Test for the Julia Olefination Reaction

41 Regeneration of the Methyl Ester…