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Le sébum, principale source de salissures grasses sur les textiles, est un mélange complexe contenant 12% de squalène, triterpène présentant 6 doubles liaisons facilement oxydables. Son oxydation par l'oxygène singulet, 1O2, conduit à la formation d'hydroperoxydes dont la décomposition libère une odeur agréable. L’objectif de l'étude était d’élucider les mécanismes mis en jeu lors de cette dégradation oxydante. Le squalène a donc été oxydé par 1O2, engendré photochimiquement et chimiquement par un système MoO42-/H2O2. La CLHP couplée à la spectrométrie de masse utilisant une technique d'ionisation par électronébullisation au lithium, a permis de détecter six familles d’hydroperoxydes, notés SQ(OOH)n avec n = 1 à 6. La RMN a montré que les hydroperoxydes secondaires et tertiaires se forment en proportions équivalentes. Puis, la dégradation thermique des hydroperoxydes de squalène a été étudiée en recourant à la RMN et à la spectrométrie de masse B-trap. 9 volatils ont été identifiés, l’acétone étant le composé majoritairement formé (de 23 à 80%). La décomposition thermique des hydroperoxydes de squalène résulte d'un mécanisme en deux étapes : formation des radicaux alcoxyles RO• et peroxyles ROO• suivi des  et -scissions produisant des aldéhydes, des alcools et des cétones. Enfin, l’activité catalytique de deux complexes ferreux à base de ligands pentadentés, le Fe-MeN4Py et Fe-bispidone, a été évaluée sur la dégradation des SQ(OOH)6. Les mêmes volatils que ceux générés par voie thermique sont alors formés mais à température ambiante, ouvrant des perspectives quant à l’exaltation de la dégradation des hydroperoxydes de squalène lors de la détergence. / The main source of fatty soils on fabrics is the human sebum including 12% of squalene, a triterpene easily oxidizable due to the presence of six unsaturations. Its oxidation by singlet oxygen, 1O2 (1Δg), leads to hydroperoxide formation whose decomposition releases a pleasant odour. The aim of this study was to clarify involved mechanisms of oxidative degradation of squalene. First, Squalene has been oxidized by singlet oxygen from photochemical and chemical way by decomposition of hydrogen peroxyde catalyzed by molybdate ions. Despite the complexity and the medium and the intrinsic fragility of performed hydroperoxides, HPLC coupled with ESI-MS-Li+, has detected six hydroperoxide families, written SQ(OOH)n with n = 1 to 6. NMR has been shown that secondary and tertiary hydroperoxides are performed in equal quantity. Then, thermal degradation of squalene hydroperoxide according their peroxidation degree has been study by B-trap mass spectrometry. 9 volatiles have been detected and identified including acetone as major compounds (23 to 80%). The thermal degradation of squalene hydroperoxide results from two-step mechanism: alkoxyl radical formation RO• and peroxyle radicals ROO• followed by α and β scissions releasing aldehydes, alcohols and ketones. Finally, catalytic activity of two ferrous complexes has been evaluated on squalene hexahydroperoxide degradation. The same volatiles as those detected by thermolysis have been released, catalyzed by bleaching agent, with the same kinetic as at 80°C but at room temperature. The use of ferrous complexes opens prospects about exaltation of squalene hydroperoxide degradation during detergency.

This thesis is concerned with studies towards the total synthesis of labiatin A using metal carbenoid chemistry. The work described herein shows the most recent contribution to this field from our research group. Chapter I provides an introduction to metal carbenoids and their uses in organic synthesis. In particular, the synthesis of diazo carbonyl compounds, their decomposition by metal catalysts leading to the formation of metal carbenoids and the reactions involving metal carbenoids is described. A retrosynthesis of labiatin A involving the use of two metal-carbenoid transformations- intramolecular C-H insertion reaction and oxonium ylide formation followed by [2,3]-sigmatropic rearrangement- is presented. In Chapter II, the successful applications of these two reactions to the enantioselective synthesis of the tricyclic core of labiatin A is described. This is followed by the description of the different attempts to complete the synthesis of labiatin A. Finally, the exploration of a modified approach to the total synthesis of labiatin A is described. Chapter III provides the analytical support to this thesis.

Thesis describes synthetic studies directed towards evaluating the biosynthetic relationships between several novel polycyclic diterpenes, including bielschowskysin 1, verrillin 2, plumarellide 3 and intricarene 4, and their probable furanobutenolide -based cembrane precursors, e.g. bipinnatin J (5) and bipinnatin G (6). These interesting natural products have all been isolated from marine corals in recent years. The Introduction describes a general overview of biologically active compounds isolated from natural sources, followed by the isolation, structure and biological profile of the aforementioned marine natural products. The Discussion section introduces the family of furanobutenolide - based cembrane natural products and then discusses the structures of bielschowskysin 1, verrillin 2, plumarellide 3 and intricarene 4 and their proposed biogenetic origins from simple furanocembranes via transannular pericyclic cycloaddition processes. A synthetic study towards the model bielschowskysin structures 106 and 132 from rubifolide analogues, i.e. 102 and 125 is then described. Difficulties with the stabilities of various substrates led to abandonment of this route, but an alternative strategy produced the 14-membered furanocembrane structure 142 which lacked a delta11,12-alkene bond. Further manipulation of 142 into the modified bielschowskysin structure 125 could not be achieved, due to the dearth of material. The oxidation chemistry of 2-alkenylfurans was next studied. Model studies established that treatment of the alkenylfuran 162 with peroxy reagents led to the Zdienedione 163. When 163 was left in the presence of p-TSA in THF-H20 it was first converted into the beta-hydroxyketone 165 and then into the vicinal diol 178, presumably via the transient enol ether species 166. In complementary studies, treatment of the Z-dienedione 163 with K2C03 in THF-H20 led to the 4-hydroxycyclopent-2-enone 193 (53%), and isomerisation in the presence of iodine gave the corresponding E-isomer 194 (90%). These observations may have significance for the origins of coralloidolide F (195) and the macrocyclic Edienedione 196 from furanocembrane precursors in corals. A brief review of the syntheses of furanobutenolide - based cembranes is presented and then two synthetic approaches towards deoxybipinnatin G (188b/ 188e), using Aldol/Stille/Nozaki-Hiyama-Kishi (NHK) and ring-closing metathesis (RCM)/StilieINHK reactions, are presented. The RCM/StillelNHK approach produced the macrocyclic precursor 275b which, unfortunately, upon exposure to CrCh in THF, produced the acyclic intermediate 318. In contemporaneous studies, attempts were made to form the furanobutenolide - based cembrane bis-deoxylopholide 319 en route to plumarellide 3, via a ReM approach. Unfortunately, exposure of the vinyl furan 322 to Grubbs 2nd generation catalyst in refluxing DCM only led to the phenylvinylfuran 338 and to the dimer 339. In a separate study, treatment of isoepilophodione B (159), derived from bipinnatin J (5) via rubifolide 49, with p- TSA in THF-H20 led to the novel and unusual 19-hydroxyrubifolide 353, presumably via the enol ether intermediate 354 and allylic transposition. The Experimental section contains full details of the preparative work carried out, and collects together spectroscopic and analytical data for all the new compounds described.

Dictyoxetane, a structurally novel diterpene, is related to the dollabellane class of natural products. Dictyoxetane contains a dioxatricyclic subunit that has never been encountered in any other natural product. This thesis describes studies towards a first total synthesis of dictyoxetane, based on a proposed intramolecular Paternò-Büchi [2+2] photocyclisation reaction between a ketone and a cyclic enol ether to generate the oxetane heterocycle of the natural product. Chapter 1 introduces the dolabellanes. The isolation, structure and proposed biosynthesis of dictyoxetane are discussed, along with existing synthetic studies towards the core dioxatricyclic ring system. Key aspects of the Paternò-Büchi reaction of alkenes with carbonyl compounds are presented. In Chapter 2 a model system, designed to test the key Paternò-Büchi [2+2] photocyclisation reaction, is proposed. A number of strategies are investigated for the overall conversion of the double bond of isopulegol into a six-membered ring enol ether. Chapter 3 describes studies towards the synthesis of the [4.3.0]-trans-hydrindane ring system contained within dictyoxetane, a structural feature that has yet to be addressed in the literature. Chapter 4 contains the experimental procedures and analytical data of all compounds prepared during the course of this study.

The cyclooctane sesquiterpene lactone, asteriscanolide 1, has attracted considerable interest in the chemical literature since San Feliciano and colleagues first reported its isolation from Asteriscus aquaticus L. To date, no pharmaceutical applications have been found for 1. However, the challenge offered by the construction of its cyclooctanoid core represents an important target for the development of methods directed towards the preparation of other related eight-membered ring-containing terpenoids with more interesting biological properties. This thesis illustrates an investigation into the total synthesis of natural product asteriscanolide 1. Following up on the previous work established by Marsh,2 an approach to 1 was designed, seeking to build a suitable framework for an intramolecular [3 + 2] nitrile oxide-olefin cycloaddition (INOC) as the pivotal synthetic step to assemble the medium-sized ring. The INOC strategy was extensively investigated. As this remained unsuccessful, the investigation was extended to various other intramolecular strategies, including intramolecular [3 + 2] silyl nitronate-olefin cycloaddition (ISOC), samarium(II) iodide-mediated cyclisation, radical-mediated cyclisation, and nitronate anion-epoxide cyclisation, which identified certain limitations that would hinder further progress. To this end, a second generation towards 1 incorporating ring-closing metathesis (RCM) and intermolecular nitronate anion-epoxide addition was designed. A detail discussion of the results is contained within.