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.

Thesis advisor: Marc L. Snapper / Chapter 1: A review of Shapiro reactions as a coupling strategy in natural product total synthesis. The syntheses of lycoramine, galanthamine, yuehchukene analogues, ovalicin, studies toward the ingenol core, haemanthidine, pretazettine, tazettine, crinamine, Taxol, colombiasin A, elisapterosin B, the AB ring fragment of spongistatin 1 and 8-epipuupewhedione are discussed. Chapter 2: The convergent total synthesis of the marine natural product norrisolide is described. Both subunits, the hydrindane core and the norrisane side chain, are prepared in an asymmetric fashion through kinetic resolution and enantioselective cyclopropanation, respectively. A Shapiro reaction couples the two fragments and a Peterson olefination installs the 1,1-disubstituted olefin. Chapter 3: Preliminary experiments to isolate the biological target of norrisolide through reductive alkylation and tritium labeling are investigated. Further experiments are proposed to shed light on the primary norrisolide-protein interactions. / Thesis (PhD) — Boston College, 2009. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: T. Ross Kelly / Total Synthesis is a field of Organic Chemistry that focuses on the construction of various compounds. These compunds can be known, such is the case in the synthesis of natural products like Lactonamycin, or they can be creations of the imagination, like the Molecular Motor. In both cases, this particular concentration of science involves a keen use of intellect as well as a substantial amount of creativity. / Thesis (BS) — Boston College, 2003. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Chemistry. / Discipline: College Honors Program.

Thesis advisor: Steven D. Bruner / Thesis advisor: Mary F. Roberts / The fuscachelins are a group of novel small molecule secondary metabolites produced by the thermophilic actinomycete <italic>Thermobifida fusca</italic>. A genome mining approach was employed to identify the fuscachelin nonribosomal peptide synthetase biosynthetic gene cluster in <italic>T. fusca</italic>. The peptide natural products were predicted to be siderophores, iron-scavenging small molecules. An assay guided fractionation approach was utilized to isolate the fuscachelins. Structure elucidation efforts employed nuclear magnetic resonance, mass spectrometric and chemical degradation techniques to determine the structure of the isolated compounds. Once the structure was known, a total synthesis was undertaken. The established synthetic route to the fuscachelins will allow for the facile development of custom-designed chemical tools for the further study of the fuscachelin biosynthetic enzymes and utilization proteins. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Vinigrol was isolated in 1987 from the fungal strain Virgaria nigra F-5408 by Hashimoto and co-workers. This compound was identified as having antihypertensive and platelet aggregation properties as well as being recognized as a tumor necrosis factor inhibitor. Aside from its interesting biological activities, vinigrol also possesses a unique structural motif consisting in a decahydro-1,5-butanonaphthalene core decorated with 8 contiguous stereocenters. Despite synthetic efforts by many research groups since its isolation, it wasn’t until 2009 that the first total synthesis of vinigrol was reported by Baran and co-workers. Herein is presented a formal synthesis of this highly compact molecule which relies upon a highly diastereoselective ketal Claisen rearrangement as the stereodefining step and an intramolecular Diels-Alder reaction to access the tricyclic structure of the molecule. (+)-Digitoxigenin is a cardiac glycoside used in the treatment of many ailments such as congestive heart failure. It is a member of the cardenolides, a sub-type of steroid containing certain structural differences such as cis A/B and C/D ring junctions, a tertiary hydroxyl group at C14 and a butenolide substituent at C17. Although a few syntheses of this class of compounds have been reported, general strategies to access their framework is scarce. Herein we report our studies towards the total synthesis of digitoxigenin which rely upon a cascading gold-catalyzed cycloisomerization (or enyne metathesis)/Diels-Alder reaction.

The cyathins are a unique group of diterpenoids produced by the birds nest fungi <i>Cyathus helenae</i>, <i>C. africanus</i>, and <i>C. earlei</i>. Several of the cyathins show strong antibiotic activity. More recently, several fungal metabolites with structures closely related to those of the cyathins have been found to be potent inducers of nerve growth factor (NGF) synthesis. The structural complexity and the exciting biological activity of the cyathane family of diterpenes have prompted our efforts to develop an efficient and general synthetic approach.<p>To date, there have been seven total syntheses and six partial syntheses of cyathins. Most of these syntheses target allocyathin B2, which does not contain the common 6-7 trans ring fusion or the hydroxyl group within the seven member ring. Modifications of these routes to provide targets with these features have not been demonstrated and may be challenging. We have developed a concise asymmetric synthesis of cyathin A3, based on the enantioselective Diels-Alder reaction of quinone (106) and diene (105). Because the transformations of cyathin A3 into other cyathins are well documented, this synthesis provides a general approach to the cyathane diterpene family. In Section 2.2, the enantioselective Diels-Alder reaction of quinone 106 and diene 105 is presented. This reaction is effectively catalyzed by a carefully prepared Mikami catalyst. It was carried out on a preparative scale to give the chiral building block 108. The absolute configuration of the Diels-Alder adduct 108 was determined by NMR and X-ray analysis.<p>In Sections 2.3-5, the enantioselective total synthesis of (-)-cyathin A3 is described. This approach features the successful oxymercuration ring opening, a newly developed in situ configuration inversion, a much improved intramolecular aldol reaction and a radical cyclization. Now envisioned in our laboratory is the development of a new access to cyathin A4, which is surmised to be possible via the intermediate prepared in this synthesis.

The cyathins are a unique group of diterpenoids produced by the birds nest fungi <i>Cyathus helenae</i>, <i>C. africanus</i>, and <i>C. earlei</i>. Several of the cyathins show strong antibiotic activity. More recently, several fungal metabolites with structures closely related to those of the cyathins have been found to be potent inducers of nerve growth factor (NGF) synthesis. The structural complexity and the exciting biological activity of the cyathane family of diterpenes have prompted our efforts to develop an efficient and general synthetic approach.<p>To date, there have been seven total syntheses and six partial syntheses of cyathins. Most of these syntheses target allocyathin B2, which does not contain the common 6-7 trans ring fusion or the hydroxyl group within the seven member ring. Modifications of these routes to provide targets with these features have not been demonstrated and may be challenging. We have developed a concise asymmetric synthesis of cyathin A3, based on the enantioselective Diels-Alder reaction of quinone (106) and diene (105). Because the transformations of cyathin A3 into other cyathins are well documented, this synthesis provides a general approach to the cyathane diterpene family. In Section 2.2, the enantioselective Diels-Alder reaction of quinone 106 and diene 105 is presented. This reaction is effectively catalyzed by a carefully prepared Mikami catalyst. It was carried out on a preparative scale to give the chiral building block 108. The absolute configuration of the Diels-Alder adduct 108 was determined by NMR and X-ray analysis.<p>In Sections 2.3-5, the enantioselective total synthesis of (-)-cyathin A3 is described. This approach features the successful oxymercuration ring opening, a newly developed in situ configuration inversion, a much improved intramolecular aldol reaction and a radical cyclization. Now envisioned in our laboratory is the development of a new access to cyathin A4, which is surmised to be possible via the intermediate prepared in this synthesis.

No description available.

Under the conditions of transfer hydrogenation employing ortho-cyclometallated iridium C,O-benzoate catalysts, selective silylallylation and CF₃-allylation were developed. In both cases, high levels of catalyst-directed enantioselectivity and diastereoselectivity were observed. Column chromatography was then tested as a new protocol to purify the iridium precatalyst; this single component precatalyst was proved to be more efficient to promote carbonyl crotylation reactions, both diastereo- and enantioselectivity were increased. Then, double asymmetric crotylation of 1,3-diols to deliver (pseudo-)C₂-symmetric adducts with exceptional level of enantioselectivity was devised. Implementation of this methodology and other hydrogenative C-C bond formations proved to be effective means for the preparation of two known polypropionate natural product fragments of C19-C25 of scytophycin C, C19-C27 of rifamycin S and the total synthesis of 6-deoxyerythronolide B. / text

Total syntheses of the neuroregenerative natural products vinaxanthone and xanthofulvin have been accomplished. The synthetic routes to both molecules utilize a highly regioselective furan Diels-Alder cycloaddition - aromatization sequence to furnish the catechol fragment present in both natural products. The pentasubstituted catechol was elaborated to a vinylogous amide which was used twice in both syntheses, exploiting the pseudosymmetry found in vinaxanthone and xanthofulvin. This approach enabled the dimerization of 5,6-dehydropolivione forming vinaxanthone, lending significant evidence to a non-enzymatically driven formation of vinaxanthone in Nature. The total synthesis of vinaxanthone was accomplished in nine steps, the shortest synthesis to date, and an additional route was devised to access a set of analogs for biological study. The first total synthesis of xanthofulvin was accomplished in 18 steps and the convergent nature of the synthetic plan allows for analog synthesis. The sets of vinaxanthone and xanthofulvin analogs will be used to examine their inhibition of Semaphorin3A, a protein which inhibits neuronal regeneration, and is the biological target for both molecules.