Cuban and Brazilian red bee propolis (CRP and BRP), a waxy red substance made by bees and found on the outside of beehives, has been used for thousands of years in folk medicine to treat a wide range of ailments. Hundreds of compounds have been isolated from CRP and BRP, however, very little is known about the individual components and their contributions to the biological activity of the propolis as a whole. Of the compounds isolated, many are simple isoflavans, complex isoflavanoids, or dimeric isoflavanoids. Herein, we report the total syntheses of isoflavanoid natural products isolated from Cuban and Brazilian red bee propolis: neovestitol, retusapurpurin A, and retusapurpurin B, as well efforts towards the total synthesis of the dimeric isoflavanoid propolone B. The synthetic strategies described will allow for biological testing on these natural products, as well unnatural analogs. Neovestitol, a simple isoflavan, has displayed interesting anti-inflammatory activity in mice. However, to the best of our knowledge, no syntheses of the natural product have been reported. Herein, we report the development of a [4 + 2] cycloaddition to access the neovestitol core. Furthermore, we developed a dynamic acylative kinetic resolution that led to the synthesis of enantiopure (S)-neovestitol. The asymmetric synthesis allowed for confirmation of the absolute stereochemistry of the isolated natural product, which had previously only been assigned based on analogy with related isoflavans. Retusapurpurins A and B are complex isoflavanoids that are often attributed with giving red bee propolis a red color. Additionally, these compounds contain a neovestitol subunit. In this thesis, we describe the development of a novel annulation promoted by bis(trifluoromethane)sulfonimide that enabled us to construct the retusapurpurin core. This methodology was used to synthesize a small library of unnatural retusapurpurin analogs. More recently, a new class of dimeric isoflavanoids were reported, propolones A-D, propolonones A-C, and propolol A. Of the eight compounds, propolones A-C and propolonones A and B contain a neovestitol subunit. Herein, we describe our efforts towards using a platinum(II)-catalyzed migratory cycloisomerization that would allow for access to these eight natural products, as well as unnatural analogs. / 2025-09-18T00:00:00Z

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The opiate alkaloid (-)-morphine and the Amaryllidaceae alkaloid (-)-galanthamine are well known for their analgesic and anticholinergic properties, respectively. The chemical feature that connects these two molecules is that they are both biosynthesized from an ortho-para phenolic oxidative coupling. Attempts to mimic this aesthetic chemistry in the laboratory for the practical production of these alkaloids have not resulted in good yields of these compounds and there is a lot of scope for improvement. Despite the enormous amount of work devoted to this area, the simple para-alkylation of an appropriately substituted phenol derivative to generate a cross conjugated 2, 5-cyclohexadienone has not been reported. This strategy would avoid the low-yielding phenolic oxidation reaction and the product would merely require a double reductive amination of the aromatic aldehyde and the latent aldehyde (in the acetal) to produce narwedine, the synthetic precursor to (-)-galanthamine. On the other hand, the same intermediate can be elaborated to (±)-morphine via a Henry reaction, followed by reduction and reductive amination. Following the aforementioned methodology, we have successfully completed the synthesis of both these alkaloids via the common intermediate, a 2, 5-cross-conjugated cyclohexadienone. A demonstration of the use of this methodology towards achieving an enantioselective synthesis of these compounds has also been made. The overall yield of the 8 step procedure for galanthamine proceeds in 65% yield, which is approximately five times the yield of the current manufacturing process for this molecule. The synthesis of (±)-morphine, for the first time, allows access to codeine without having to reduce codeinone and, with an overall yield of 20% for the 14 step process, makes this the shortest synthesis of morphine. / text

Merrilactone A (1) was isolated in only 0.004% yield from the methanol extracts of the pericarps of Illicium merrillianum. Structural elucidation of Merrilactone A revealed a compact, cage-like pentacyclic architecture of high molecular complexity, featuring seven stereocentres, five of which as contiguous fully substituted carbon atoms, two γ-lactones and a central oxetane ring. Merrilactone A also exhibits an important neurotrophic activity, significantly promoting neurite outgrowth in the primary cultures of foetal rat cortical neurons at very low concentrations. Structurally, merrilactone A is related to anislactones A and B, a pair of epimeric sesquiterpene dilactones discovered ten years earlier by Kouno and co-workers from the related Illicium anisatum plant. Fukuyama has shown that anislactone B can be converted into merrilactone A using a simple three step sequence, suggesting that the anislactones may be biogenetic precursors to merrilactone A. Described in this thesis are our research efforts directed towards developing a conceptually novel synthetic route enabling regiodivergent total synthesis of both anislactone A / B and merrilactone A. Our synthetic route (around 22 steps) features several key reactions, which include a [2+2] photo-cycloaddition reaction, Tiffeneau-Demjanov ring expansion and titanium(III) mediated radical cyclization.

This thesis is concerned with the development of ring-closing iodoamination and ringexpansion methodology and its subsequent application to the asymmetric syntheses of pyrrolidine and piperidine iminosugars. <strong>Chapter 1</strong> highlights the remarkable biological properties displayed by iminosugars and introduces methods for the formation of the pyrrolidine and piperidine sub-classes. <strong>Chapter 2</strong> describes investigations into the ring-closing iodoamination of bishomoallylic amines which occurs with concomitant <i>N</i>-debenzylation to give an iodomethyl pyrrolidine scaffold. Conversion to the corresponding aziridinium species followed by its regioselective intermolecular ring-opening by H₂O enabled the synthesis of (+)-2,5-dideoxy-2,5-imino-Dglucitol (DGDP). A protocol for the preparation of its 1-deoxy-1-amino analogue (+)-ADGDP was also developed. <strong>Chapter 3</strong> details studies into the ring-expansion of iodomethyl pyrrolidine scaffolds via the trapping of CO₂ (from NaHCO₃) to produce cyclic carbonates as single diastereoisomers. Subsequent deprotection of these piperidines allowed the syntheses of (−)-1-deoxymannojirimycin (DMJ) and (+)-1-deoxyallonojirimycin (DANJ) to be completed. <strong>Chapter 4</strong> delineates investigations into the trapping of alternative “X=C=Y” electrophiles, via the ring-expansion methodology developed in Chapter 3, initially utilising a model system. These studies culminated in the development of the trapping of <i>p</i>-TsNCO and the application of this methodology in the total asymmetric syntheses of (−)-ADMJ and (+)-ADANJ, the 2-deoxy-2-amino analogues of (−)-DMJ and (+)-DANJ, respectively. <strong>Chapter 5</strong> contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3 and 4.

Thesis advisor: Jason Kingsbury / Recent findings have led to the discovery that the Sc-catalyzed addition of substituted diazoalkanes to aldehydes elegantly affords a net carbon insertion into the C-H bond, delivering the requisite ketone in one simple step with no need for a readjustment in oxidation state. This chemistry is much improved over the century old diazomethane chemistry which requires stoichiometric amounts of a promoter and is limited in both application and scope. The new catalytic method has now been utilized as the key step in the synthesis of the pseduosymmetric precursor to the natural product achyrofuran, which has been named “pre-achyrofuran.” Subsequently, a related project was pursued involving the desymmetrization of bicyclic β-diketones by catalytic carbon insertion with trimethylsilyldiazomethane as the reagent. Preliminary developments in this area are disclosed. / Thesis (BS) — Boston College, 2010. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Chemistry Honors Program. / Discipline: Chemistry.

This thesis describes the development of new thermal and oxidative radical cyclization methodologies and their application to the total syntheses of alkaloids, particularly to bridged diketopiperazine (DKP) alkaloids. A practical solvent free approach to diverse DKPs and quinazolines is described. The methodology proceeds by thermal silica gel mediated deprotection of the Boc protecting group and intramolecular condensation of the resulting free dipeptides and tripeptides. It was applied to the total syntheses of alkaloids glyantrypine and ardeemin. A major part of the thesis concerns with the discovery and applications of novel diketopiperazine derived alkoxyamines. Their propensity to undergo facile thermal C-O bond homolysis to generate captodative DKP radicals and persistent TEMPO radical allowed using them as radical surrogates. The methodology takes advantage of the persistent radical effect (PRE). The methodology based on PRE was applied in an asymmetric approach to the alkaloid asperparaline C. An asymmetric synthesis of a very advanced precursor to asperparaline C, 8- oxoasperparaline C, was accomplished in 11 steps and 15% overall yield. The key steps of the synthesis include a direct oxidative cyclization of DKPs, regioselective furan dearomatization with singlet oxygen and a reductive...

Thesis advisor: Marc L. Snapper / A survey of silicon-based reactions and potential for Lewis base catalysis was presented. An efficient site- and enantioselective catalytic silylation of triols is disclosed. The protocol is applied to total syntheses of cleroindicins D, F and C. Catalytic kinetic resolution of &#946;-hydroxyketones is disclosed. A readily available amino acid-based catalyst promotes the kinetic resolution with high efficiency. A presentation of catalytic enantioselective tosylation of syn-1,2-diols is disclosed. / Thesis (PhD) — Boston College, 2009. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: T. Ross Kelly / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: James P. Morken / (+)-Discodermolide is a marine natural product and is one of the most potent microtubule stabilizers in human cell lines. Because of its unique linear structure and important properties, a number of total syntheses of (+)-discodermolide and its derivatives have been reported. Herein, an efficient, highly convergent, and stereocontrolled total synthesis is presented (Chapter 2). The synthesis relied on the development of three catalytic and stereoselective processes: platinum-catalyzed asymmetric diene diboration, nickel-catalyzed diastereoselective hydroboration of chiral dienes (Chapter 1), and nickel-catalyzed borylative diene-aldehyde coupling (see Chapter 4). Combination of these reactions allows preparation of the target in a short sequence. Moreover, the development of rhodium-catalyzed asymmetric hydroformylation (Chapter 3) makes this approach the first Roche ester free (+)-discodermolide synthesis. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.