Enantioselective formal synthesis of ent-rhynchophylline and ent-isorhynchophylline

Starting from (S)-tryptophanol, a formal synthesis of ent-rhyncho-phylline and ent-isorhynchophylline, involving stereoselective cyclocondensation, spirocyclization, and alkylation reactions, and the final adjustment of the oxidation level at the oxindole and piperidine moieties, is reported.

Enantioselective formal synthesis of ent-rhynchophylline and ent-isorhynchophylline

Starting from (S)-tryptophanol, a formal synthesis of ent-rhyncho-phylline and ent-isorhynchophylline, involving stereoselective cyclocondensation, spirocyclization, and alkylation reactions, and the final adjustment of the oxidation level at the oxindole and piperidine moieties, is reported.

Stereodivergent approach to the asymmetric synthesis of bacillariolides: A formal synthesis of ent-bacillariolide II

Asymmetric synthesis of densely functionalized bicyclic frameworks for entry into bacillariolides I/III and ent-bacillariolide II is reported. The key features are ring-closing metathesis of a pair of diastereomerically related dienes obtained through a stereodivergent route from a R-(+)-glyceraldehyde derivative, transformation of a nonstereoselective cyclopentene ester enolate alkylation process to a completely stereoselective one through alkylation of a bulky ester enolate with a bulky electrophile, and a remote silyloxymethyl group directed epoxidation.

alpha,beta-Unsaturated Diazoketones as Platforms in the Asymmetric Synthesis of Hydroxylated Alkaloids. Total Synthesis of 1-Deoxy-8,8a-diepicastanospermine and 1,6-Dideoxyepicastanospermine and Formal Synthesis of Pumiliotoxin 251D

A versatile and concise approach for the stereoselective synthesis of mono-, di-, and trihydroxylated indolizidines is presented in four to six steps from Cbz-prolinal and a diazophosphonate. The key steps involved a Wolff rearrangement, followed by a stereoselective dihydroxylation/epoxidation reaction, from an alpha,beta-unsaturated diazoketone. The strategy also permits extension to the synthesis of many natural hydroxylated indolizidine alkaloids as demonstrated in the formal synthesis of pumiliotoxin 251D.

The pathology of command and control: a formal synthesis

One of the most important theories in the study of environmental governance and policy is the pathology of command and control, which describes the negative consequences of top-down, technocratic governance of social and ecological systems. However, to date, this theory has been expressed somewhat inconsistently and informally in the literature, even by the seminal works that have established its importance and popularized it. This presents a problem for the sustainability science community if it cannot be sure of the precise details of one of its most important theories. Without such precision, applications and tests of various elements of the theory cannot be conducted reliably to advance the knowledge of environmental governance. I address this problem by synthesizing several seminal works to formalize this theory. The formalization involves the identification of the individual elements of the theory and a diagrammatic description of their relationships with each other that unfold in a series of semi-independent causal paths. Ideally, with such a formalization, scholars can use this theory more reliably and more meaningfully in their future work. I conclude by discussing the implications this theory has for the governance of natural resources.

Synthesis of potassium and tetra n-butylammonium 2-substituted-1,3-dithianotrifluoroborate salts and addition to chiral cyclic N-acyliminium ions

The synthesis of potassium 2-substituted-1,3-dithianotrifluoroborate salts and tetra-n-butyl ammonium derivatives is described. The reaction proceeds under mild reaction conditions and the corresponding products were obtained in moderate to good yields. The reactivity of these compounds in rections with chiral cyclic N-acyliminium ions was evaluated.

Enantiodivergent chemoenzymatic synthesis of Balanol and approaches to the synthesis of (+)-Codine

The present thesis reviews the development of a formal enantiodivergent synthesis of the (+)- and (-)-isomers of balanol. This approach commences from a cis-dihydrodiol derived from the enzymatic dihydroxylation of bromobenzene. The stereochemistry of the diol is used to direct the synthesis of two different aziridines, each used in the formal synthesis of one enantiomer of balanol. Also described are several enantioselective approaches to (+ )-codeine. Each strategy begins with the enzymatic dihydroxylation of p-bromoethylbenzene and involves a Mitsunobu inversion and intramolecular Heck reaction as key steps.

Two enantiodivergent syntheses of balanol and the chemoenzymatic synthesis of oseltamivir

The present thesis outlines our latest findings on the reactivity of the Burgess reagent with oxiranes. Structural, mechanistic, and computational studies are presented. Included is the development of a (-)-menthyl version of the Burgess reagent and its application to the synthesis of enantiomerically pure ~-amino alcohols. This methodology has been exploited in the formal enantiodivergent synthesis of the (+)- and (-)-isomers of balanol. Also described is a second generation approach to both balanol enantiomers; each commencmg with the chemoenzymatic dihydroxylation of bromobenzene. This study also describes the steric and functional limitations of the toluene dioxygenase-mediated oxidation of benzoate esters. The metabolite derived from ethyl benzoate was employed in a formal synthesis of oseltamivir. Finally, several synthetic approaches to oseltamivir and its analogs are presented, each proceeding through a different vinyl aziridine derived from bromobenzene and ethyl benzoate.

A new route to furanoeremophilane sesquiterpenoids. Synthesis of Senecio metabolites (+/-)-6-hydroxyeuryopsin, (+/-)-1,10-epoxy-6-hydroxyeuryopsin, (+/-)-toluccanolide A and (+/-)-toluccanolide C

A new strategy for the synthesis of sesquiterpenoids of the furanoeremophilane family was developed in which the tricyclic nucleus was assembled in an A + C -> A - C -> A - B - C sequence. The A - C connection was made via coupling of a cyclohexenylmethyl bromide with a stannylfuran under "ligandless" Stille conditions, and the key cyclization which closed ring B was accomplished with complete stereocontrol by intramolecular formylation of a 2-silylfuran in the presence of trimethylsilyl triflate. This route was used to complete the first total syntheses of the furanoeremophilane 6-hydroxyeuryopsin and the eremophilenolides toluccanolide A and toluccanolide C, as well as a formal synthesis of 1,10-epoxy-6-hydroxyeuryopsin.

Intramolecular Diels-Alder furan-mediated synthesis of 8-aryl-3, 4-di-hydroisoquinolin-1(2H)-ones, convenient precursors of indeno[1,2,3-ij]isoquinolines

We describe herein preliminary studies on the Intramolecular Diels-Alder Furan-Mediated Synthesis of 8-Aryl-3, 4-di-hydroisoquinolin-1(2H)-ones that constitutes a new, formal synthesis of Indeno[1,2,3-ij]isoquinolines.

Tellurium in organic synthesis: a new approach to trisubstituted gamma-butyrolactones with trans-trans relative stereochemistry. Total enantioselective synthesis of (-)-Blastmycinolactol, (+)-Blastmycinone, (-)-NFX-2, and (+)-Antimycinone

The total synthesis of (-)-Blastmycinolactol, (+)-Blastmycinone, (-)-NFX-2, and (+)-Antimycinone was accomplished in few steps in high yields and ee, starting from enantiomerically enriched (S)-Z-vinylic hydroxytellurides. (C) 2010 Published by Elsevier Ltd.

Synthèse formelle de l’hormaomycine et de la bélactosine A par utilisation d’une réaction de cyclopropanation intramoléculaire catalysée par un complexe de rhodium (II)

Ce mémoire présente trois approches différentes vers la synthèse du 3–(trans–2–nitrocyclopropyl)alanine, un intermédiaire synthétique de la hormaomycine. Cette molécule naturelle démontre d’intéressantes activités biologiques et pharmacologiques. Il est intéressant de souligner que ce dérivé donne facilement accès au 3–(trans–2–aminocyclopropyl)alanine, unité centrale de la bélactosine A. Ce composé naturel possédant lui aussi d’intéressantes propriétés biologiques, plusieurs études relationnelles structures-activités menant à des dérivés plus actifs de cette molécule ont été entreprises, démontrant l’intérêt toujours présent de synthétiser de façon efficace et optimale ces dérivés cyclopropaniques. Une méthodologie développée au sein de notre groupe de recherche et basée sur une réaction de cyclopropanation intramoléculaire diastéréosélective sera mise à profit afin d’élaborer une nouvelle voie de synthèse aussi élégante qu’efficace à la construction du 3–(trans–2–nitrocyclopropyl) alanine. En utilisant un carbène de rhodium généré soit par la dégradation d’un dérivé diazoïque, soit par la formation d’un réactif de type ylure d’iodonium, une réaction de cyclopropanation diastéréosélective permettra la formation de deux autres centres contigus et ce, sans même utiliser d’auxiliaire ou de catalyseur énantioenrichis. Ensuite, un réarrangement intramoléculaire précédant deux réactions synchronisées d’ouverture de cycle et de décarboxylation permettront l’obtention du composé d’intérêt avec un rendement global convenable et en relativement peu d’étapes. De cette manière, la synthèse formelle de la bélactosine A et de l’hormaomycine a été effectuée. Cette synthèse se démarque des autres par l’utilisation d’une seule transformation catalytique énantiosélective.