Thèse de doctorat en sciences physiques. Chimie
Sous la direction de Derek Harold Richard Barton.
Soutenue en 1985
à Paris 11 , en partenariat avec Université de Paris-Sud. Faculté des sciences d'Orsay (Essonne) (autre partenaire) .
Structure, biosynthesis and synthesis of new biologically active acetogenins produced by the fungus Phoma lingam Tode : new orientation of carbene-phenol chemistry : discovery of new synthesis reactions of cyclohexadienones, tropones and tropolones
The discovery of two new biologically active metabolites from the mycelium of the fungus Phoma lingam is at the origin of this thesis. After the completion of their structural elucidation, synthetic efforts lead to the discovery of several new reactions. Identification of these two metabolites phomenoic acid and its 6-lactone are based on spectroscopic as well as chemical studies. Further support for their structure comes from biosynthetic studies. The synthesis of α,γ-dienol γ-hydroxymethyl which represents a fragment of their skeleton is achieved by a new and elegant synthetic approach which involves photochemical opening of the 6-alkoxymethyl cyclohexa-2,4 dienone. Efforts towards the synthesis of these cyclohexadienones gave an opportunity to oriente the "carbene-phenol" chemistry. Furthermore ortho-alkoxymethylation of these suitably substituted phenols is accomplished by another new method where triphenylphosphine acts as a catalyst. A further significant contribution is the discovery of a synthesis of tropones and tropolones. This new reaction involves tri-n-butyltin hydride reduction of mono-, di- and trihalomethyl cyclohexadienones. New methods for the synthesis of these cyclohexadienones are described along with the reaction mechanism for their reduction.