Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2009. / Includes bibliographical references (p. 74-81).

Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 223-236).

"July 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

Correlation of adsorption behavior for a gas-surface system to the molecular structure of the gas-phase molecule is necessary to better constrain atmospheric modeling. Despite the variety of compounds emitted into the atmosphere, the role of molecular structure on uptake probability, γ, for a compound adsorbing onto a surface is not well understood. A custom designed flow manifold coupled to a mass spectrometer provides the means to analyze changes in γ for gases at environmentally relevant low ppb concentrations. Studies have focused on the adsorption of two classes of compounds: singly substituted benzene derivatives and several terpenoid compounds for a silica surface composed of hydroxyl groups and bridging oxygen species. Results for benzene derivatives show an enhancement of the initial γ value of all functionalized compounds relative to benzene, with this initial value influenced by both the dipole and volatility of a compound. The time-dependent behavior of γ has been shown to depend on the interactions occurring between the adsorbate and surface with species capable of hydrogen bond interactions exhibiting a greater number of adsorbed species at equilibrium. The initial γ value for terpenoid species was observed to increase from isoprene to sesquiterpenes, with several monoterpene isomers exhibiting distinct adsorption behavior based on structural differences. The sesquiterpene examined, β-caryophyllene, exhibited continuous uptake onto the silica surface and such uptake behavior could contribute in part to the low concentrations of sesquiterpenes observed in the environment. Encapsulation of the hydroxyl groups resulted in decreased uptake of several aromatic and terpenoid species examined and indicates that hydroxyl groups represent the majority of adsorption sites for the systems examined. Comparison between observed uptake behavior to adsorption models exhibited the best agreement with a model depicting monolayer formation with cooperative adsorption due to interactions between adsorbates. Formulations for predicting initial γ values based on the volatility and dipole of the compound are provided. Overall, these results represent the first step towards a better understanding of gas-surface interactions that occur in the environment. Sesquiterpenes represent one class of biogenic emissions not well constrained with regards to SOA influence due to their low volatility and concentrations relative to more abundant terpenoid species. Ambient measurements of sesquiterpenes through the Semi-Volatile Thermal desorption Aerosol Gas chromatography (SV-TAG) instrument presented total sesquiterpene concentrations that ranged from 0.8 to 2 ppt with no isomer dominating. Sesquiterpene contribution towards hydroxyl reactivity is negligible in comparison to more abundant terpenoid species while ozone reactivity was dominated by two isomers and could contribute to atmospheric reactivity during periods of high emissions. These measurements represent the first step in better constraining the contribution of sesquiterpenes towards secondary organic aerosol formation. / Doctor of Philosophy / A large variety of compounds are emitted into the atmosphere from natural and human sources. The molecular structures of these compounds are complex and differences in structure can alter the environmental fate of compounds, which can directly affect human health. While atmospheric modeling provides insight into the fate of compounds, it relies on experimentally determined values for accuracy. The probability that a gas-phase molecule "sticks" to a surface upon collision, defined as the uptake probability, represents one value that is not well understood. My research has primarily focused on the development and testing of an instrument capable of observing gas uptake onto a surface for environmentally relevant gas concentrations. This has included understanding how differences in structure of a molecule affect adsorption for a single surface. For example, α-pinene and β-pinene (both compounds emitted by plants and found in air fresheners!) exhibit distinct adsorption behavior that arises from the location of a single carbon-carbon double bond for the same structure. Similarly, making a "water-loving" surface into a "water-repelling" surface results in less α-pinene adsorbed, despite α-pinene being considered insoluble in water. The developed instrument represents a vital tool in improving the accuracy of atmospheric modeling. In addition to understanding gas adsorption onto a surface, my research has focused on the detection and quantification of one class of naturally emitted compounds in Virginia: sesquiterpenes. These compounds are emitted by plants for a variety of reasons, and their influence on particle formation is not well understood. Measurement of sesquiterpenes at two sites in Virginia provides a better understanding of the abundance of sesquiterpenes in geographic regions not previously analyzed. These measurements contribute to an increased understanding of the role of different compound classes on particle formation in the atmosphere.

Among Nature's creation, terpenoids are more versatile and exciting natural products. In a remarkable display of synthetic ingenuity and creativity, nature has endowed terpenes with a bewildering array of carbocyclic frameworks with unusual assemblage of rings and functionalities. This phenomenal structural diversity of terpenes makes them ideal targets for developing and testing new synthetic strategies for efficient articulation of carbocyclic frameworks. The thesis entitled “Synthetic Approaches to Herbertenoid and Cuperenoid Sesquiterpenes" describes the application of ring-closing metathesis and Claisen rearrangement based approach to some herbertenoid and cuparenoid natural products. The results are described in five different sections, viz., a) First Total Synthesis of (±)-γ-Herbertenol; b) First Total Synthesis of (±)-HM-2; c) First Total Synthesis of (±)-HM-4 and HM-3; d) First Total Synthesis of Herbertenones A and B; and e) Total Synthesis of Lagopodin A. Complete details of the experimental procedures and the spectroscopic data were provided in a different section. A brief introduction is provided wherever appropriate to keep the present work in proper perspective. The compounds are sequentially numbered (bold), references are marked sequentially as superscripts and listed in the last section of the thesis. All the spectra included in the thesis were obtained by xeroxing the original NMR spectra. To begin with, the first total synthesis of γ-herbertenol, an herbertene isolated from a non-herbertus source, has been accomplished starting from 3,5-dimethylphenol. Claisen rearrangement of 3-(3-methoxy-5-methylphenyl)but-2-en-1-ol, obtained in eight steps from 3,5-dimethylphenol, furnished a γ,δ-unsaturated ester, which was transformed into 4-aryl-4,5,5-trimethylcyclopent-2-enone employing RCM reaction as the key step, which was further transformed into (±)-γ-herbertenol, which exhibited spectral data identical to that of the natural product. An alternative RCM reaction based methodology was also developed for the synthesis of γ-herbertenol methyl ether starting from ethyl 3-aryl-3-methylpent-4-enoate, an intermediate in the first sequence. The methodology has been extended for the synthesis of the putative structure of HM-2 starting from 2,4-dimethoxy-5-methylacetophenone via the corresponding ethyl 3-aryl-3-methylpent-4-enoate. However, the spectral data of the synthetic compound was found to be different from that reported for the natural product. A new cuperenoid structure for HM-2 was proposed. Total synthesis of cuparene-1,4-diol starting from toluhydroquinone, followed by its conversion to mono methyl ether and mono acetyl derivative confirmed the structures of HM-1 and the revised structure of HM-2. In a similar manner, total synthesis of the putative structure of HM-3 starting from 4-methylresorcinol dimethyl ether proved it to be wrong. A cupereniod structure, HM-4 monoacetate was proposed for HM-3. Synthesis of HM-4, and its conversion to mono acetate confirmed the structures of HM-4 and the revised structure of HM-3. The methodology has been further extended to the first total synthesis of herbertenones A and B starting from 2,5-dimethoxybenzaldehyde. By readily identifying the similarity between lagopodin A and HM-1 and HM-2, an intermediate in the synthesis of HM-1 and HM-2 has been further transformed in to (±)lagopodin A.

Nesta tese, efetuamos estudos visando à síntese de sesquiterpenos bacanos, cuja etapa chave consistiu na construção do sistema cis-hidrindânico, através de reação de contração de anel de cis-octalinas e 2-octalonas mediada por trinitrato de tálio (TTN). Apenas as cis-octalinas como, por exemplo, o cis-4a-metil-l,2,3,4,4a,5,8,8a-octahidronaftaleno e o cis-4a, 7-dimetil-l,2,3,4,4a,5,8,8a-octa-hidronaftaleno, foram passíveis de reação de contração de anel em rendimentos satisfatórios; já a cis-5,10-dimetil-l(9)-octal-2-ona levou ao produto de contração em baixo rendimento. Tentamos utilizar a reação de cis-4a-metil-l,2,3,4,4a,5,8,8a-octa-hidronaftaleno com TTN na síntese da nor-baquenolida-A, porém não conseguimos completar a síntese desta, pois não foi possível efetuar a última etapa sintética, nas várias abordagens testadas. Grandes esforços também foram empregados na preparação diastereosseletiva da cis-5,10-dimetil-l(9)-octal-2-ona através de três abordagens diferentes que foram investigadas, sendo duas delas com êxito. Contudo, o baixo rendimento (38%) da etapa de contração de anel da cis-5,10-dimetil-l(9)-octal-2-ona não permitiu a continuação da rota sintética proposta para a baquenolida-A. Também realizamos a resolução cinética de três diferentes cis-octalóis que foram preparados através da reação de Diels-Alder seguida de redução diastereosseletiva - com a lipase Novozym 435, e os produtos resolvidos foram obtidos em excelentes rendimentos isolados (≥ 40% para cada enantiômero) e excelentes excessos enantioméricos (≥ 98%). / In this thesis, we have developed studies towards the synthesis of sesquiterpenes bakkanes, which key step consisted on the construction of the cis-hydrindanic system through a thallium(III) mediated ring contraction reaction of cis-decalins and 2-octalones. Only the cis-octalins, such as the 1,2,3,4,4a,5,8,8a-octahydro-4a-methylnaphthalene and the 1,2,3,4,4a,5,8,8a-octahydro-4a,7-dimethylnaphthalene, were able to be ring contracted in satisfactory yields; the 4,4a,5,6,7,8-hexahydro-4a,5-dimethylnaphthalen-2(3H)-one, however, furnished the ring contraction product in low yield. We tried to use the reaction of 1,2,3,4,4a,5,8,8a-octahydro-4amethylnaphthalene with TTN in the synthesis of nor-bakkenolide-A, but we could not accomplish the synthesis because it was not possible to make the last step of the sequence, in all tested approaches. Great efforts were made in the diastereoselective preparation of the 4,4a,5,6, 7 ,8-hexahydro-4a,5-dimethylnaphthalen-2(3H)-one, through three different approaches that were investigated, being two of them with profit. However, the low yield (38%) of the ring contraction reaction of 4,4a,5,6, 7,8-hexahydro-4a,5-dimethylnaphthalen-2(3H)-one, precluded the continuation of the synthetic rout proposed to the bakkenolide-A. We have also performed the kinetic resolution of three different cis-octalols that were prepared through Diels-Alder reaction followed by diastereoselective reduction - with the Novozym 435 lipase, and the resolved products were isolated in excellent yields (≥ 40% for each enantiomer) and excellent ee\'s (≥ 98%).

Chapter 1. Ring-Opening Knoevenagel Strategy for the Synthesis of Alpha-Carboalkoxy Cyclopentenones and Their Use in the Diels-Alder Cycloaddition. The Diels-Alder reaction has enabled the synthesis of hundreds of natural products efficiently and with high levels of stereocontrol. Despite over eight decades of development, this reaction is incapable of forming hydrindane ring junctions from alphahydro beta-alkyl cyclopentenones. As such, we used alpha-carboalkoxy cyclopentenones as synergistic dienophiles, but exposed a lack of synthetic tools for assembling strained bicyclic cyclopentenones. We addressed this paucity by developing a ring-opening Knoevenagel reaction for synthesizing these synergistic dienophiles with varying degrees of substitution. The 6 step protecting group free total synthesis of a structurally similar natural product merrekentrone D was achieved to demonstrate the utility of the new method. In addition, the Diels-Alder cycloaddition with these molecules with the Danishefsky-Kitahara diene were studied. The variability of the ring-opening Knoevenagel reaction also led to the development of a decarboxylative Diels-Alder cycloaddition which is degenerate with the alpha-hydro beta-alkyl cyclopentenone Diels- Alder reaction. The hydrindane structures are referred to as iso-Hajos-Parrish ketones which we subsequently demonstrate as powerful building blocks for natural product total synthesis. Chapter 2. Synthetic Studies Towards the Shizukaol Family of Oligomeric Sesquiterpene Natural Products The shizukaol family of oligomeric natural products are one of three oligomeric sesquiterpene families. Three different generations of synthetic strategies towards the unstable and dimeric precursor lindenatriene were studied. The use of the iso-Hajos-Parrish ketone enabled a 10 step, protecting group free, total synthesis of the intermediate. In addition the formation of unnatural dimers was achieved as well as several unexpected results which led to the generalization of our strategy to other natural product families. Chapter 3. Iso-Hajos-Parrish Ketones: Common Intermediates for Sesquiterpene Total Syntheses The three step synthesis of the cyclopropane substituted iso-Hajos-Parrish ketone enabled rapid access to other sesquiterpene families. Through reductase phases the total synthesis of sarcandralactone was achieved in 10 steps without the use of any protecting groups. Studies were also conducted towards achieving the trans-hydrindane ring as a synthetic equivalent to a trans-Diels-Alder paradigm, which was not realized. Additionally, cyclopropane opening of the iso-Hajos-Parrish ketone led to highly oxidized eudesmane skeletons. Our attempts to hydrogenate these molecules in the reductase phase inspired a 6 step total synthesis of des-methyl pinguisone with a strikingly different sesquiterpene framework. Finally, an analysis of redox conservation in total synthesis and the generality of this chemistry to the total synthesis of sesquiterpene natural products will be presented.

Graduation date: 1997

Graduation date: 1993