The synthesis of the nitrogen containing heterocyclic compounds is one of the leading research areas throughout the organic chemistry due to their significant activities in biological systems. Among the various biologically active molecules, pyridine-fused ring systems are of prime importance on the grounds of their proven clinical roles. The coupling reactions with 6-membered heterocyclic compounds and diazepines gave rise to new pharmalogical compounds in recent years. Therefore, our object was the synthesis of pyridine-fused 6- and 7-membered heterocycles. Starting from bromopyridine, two different methods were applied for the synthesis of target compounds. In the first part of the this thesis, coupling products were synthesized using Sonogashira coupling reaction. After synthesis of the coupling derivatives, ring-closure under the basic conditions generated the heterocyclic units without using any catalyzer. In the second part of study, nicotinic acid and pyridopyranone derivatives were synthesized by using intramolecular cyclization reactions. The formed products were conscientiously purified and characterized by means of spectroscopics method.

Made available in DSpace on 2014-06-12T23:03:42Z (GMT). No. of bitstreams: 2 arquivo963_1.pdf: 3737441 bytes, checksum: 889830aefa59c6dbf6eb43d1d652f5db (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2010 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / A Combretastatina D-2 é uma macrolactona isolada em 1989 da árvore sul africana Combretum caffrum. A partir de 77 Kg da casca foram obtidos 5,8 mg do produto natural - um rendimento de 7,5 × 10-6 %. Este composto exibiu atividade antineoplásica sobre células leucêmicas P-388 ao impedir a desmontagem dos microtúbulos durante a mitose celular. O mecanismo de ação incomum tornou a Combretastatina D-2 um alvo de permanente investigação na farmacologia anticâncer. Assim, com o desejo de contribuir com as investigações sobre esta macrolactona, neste trabalho é proposta a investigação de uma nova estratégia de síntese para a preparação deste produto natural. A estratégia sintética proposta foi baseada no acoplamento de dois fragmentos principais: A e B. O fragmento A consistiu em um composto de boro, sintetizado na forma de um ácido borônico ou um trifluoroborato de potássio em rendimentos globais moderados. Para a preparação do fragmento B, um fenol, foram envolvidas reações de acoplamento do tipo Sonogashira e reação de hidrogenação catalítica

Cross coupling reactions are a well-established tool in modern organic synthesis and play a crucial role in the synthesis of a high number of organic compounds. Their importance is highlighted by the Nobel Prize in chemistry to Suzuki, Heck and Negishi in 2010. The increasing importance of sustainability requirements in chemical production has furthermore promoted the development of cross-coupling protocols that comply with the principles of “Green Chemistry”1. The Sonogashira reaction is today the most versatile and powerful way to generate aryl alkynes, a moiety recurring in many pharmaceutical and natural products. Despite many improvements to the original reaction, reports on generally applicable protocols that work under sustainable conditions are scarce. Our group recently reported an efficient protocol for a copperfree Sonogashira cross-coupling at low temperature, in aqueous medium and with no addition of organic solvents or additives2. The goal of this work was to further investigate the effects of different reaction parameters on the catalytic activity in order to optimize the protocol. Limitations of the protocol were tested in respect to reaction temperature, heating method, atmosphere, base type and amount, catalyst loading, reaction time and work up procedure. The reaction worked successfully under air and results were not affected by the presence of oxygen in the water phase. Among a variety of bases tested, triethylamine was confirmed to give the best results and its required excess could be reduced from nine to four equivalents. Catalyst loading could also be reduced by up to 90%: Good to near quantitative yields for a broad range of substrates were achieved using a catalyst concentration of 0.25mol% and 5 eq of Et3N at 50°C while more reactive substrates could be coupled with a catalyst concentration as low as 0.025mol%. Filtration experiments showed the possibility of a simplified work up procedure and a protocol completely free of organic solvents. This optimized protocol can be applied to a broad range of substrates, delivers high yields, avoids formation of toxic byproducts, works under air and aqueous conditions, allows for simple product isolation and thus meets not only the criteria of “Green Chemistry” but also those of “Click-Chemistry”

Cette étude présente la conception d’agents pour la radiothérapie et la Tomographie par Emission de Positrons (TEP). Les agents bimodaux envisagés sont constitués de deux parties : la partie uracile et la partie diamsar (1,8-diamino-3,6,10,13,16,19- hexaazabicyclo[6.6.6]eicosane) qui complexerait le 64Cu2+ ou le 67Cu2+. Durant la conception de ces agents bimodaux, nous avons examiné indépendamment les deux parties. Dans un premier temps, l’introduction de différents groupements benzyliques sur les amines primaires du diamsar ont permis d’étudier les changements dans les propriétés de complexation des ions métalliques (Cu2+, Co2+ et Cd2+) par les ligands. Quant aux dérivés correspondant à la partie uracile, leur stabilité a été étudiée à pression atmosphérique puis dans un système de vide à très basse pression par entraînement dans un jet d’hélium. Lors de l’introduction à leur état gazeux par le jet d’hélium, aucune dissociation thermique ne fut observée par spectrométrie de masse couplée avec la technique de « time of flight ». La réussite de cette introduction démontre clairement que les études d’interactions entre l’électron ou le positron de basse énergie et ces dérivés de l’uracile peuvent être réalisées pour des études ultérieures de l’attachement dissociatif des électrons ou de l’annihilation de positron. / The design of PET-radiotherapy agent investigation is reported. These envisaged bimodal agents are based on two moieties: the uracil moiety and the diamsar (1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane) moiety that could complex 64Cu2+ or 67Cu2+. In the design of bimodal agents, the two moieties are investigated independently. Firstly, diamsar derivatives with various benzyl groups linked to the primary amines are synthesized. Therefore, the influence of these changes on the complexation of metal ions (Cu2+, Co2+ and Cd2+) is established. In the other hand, the stability of the synthesized uracil derivatives is first investigated at atmospheric pressure followed by their introduction into a high vacuum system by seeding into a helium jet. Through time of flight mass spectroscopy (TOFMS), no thermal dissociation is observed in their gas phase during the heating phase of introduction in the helium jet. This successful introduction clearly demonstrates that interaction studies between low energy electron or positron and these uracil derivatives could be performed for dissociative electron attachment (DEA) or positron annihilation studies.

In dieser Studienarbeit wird die Entwicklung eines CuI- bzw. NiII-Komplexes mit bidentaten Ferrocenylliganden dargelegt und der eventuelle Einsatz als Katalysator für Palladium-analoge C-C-Kupplungsreaktionen diskutiert. Als Ausgangspunkt dieses Entwicklungsprozesses werden im Abschnitt 2. zunächst eine Reihe ausführlicher theoretischer Vorbetrachtungen getätigt. Diese beinhalten u. a.: - Mechanismus der Palladiumkatalyse, erläutert am Beispiel der Sonogashira-Hagihara-Reaktion (Abschnitt 2.1.) - Vorstellung der Nickelkatalyse und Erläuterung des möglichen Ni0-NiII-Mechanismus am Beispiel der Mizoroki-Heck-Reaktion inklusive Vergleich zur Palladium-katalysierten Variante. Des Weiteren wird das NiI-NiIII-System beschrieben (Abschnitt 2.2.) - Vorstellung bekannter Kupfer-katalysierter Reaktionen und mechanistische Betrachtung des System CuI-CuIII (Abschnitt 2.3.) - kurze Einführung in das Themengebiet Ferrocenylliganden (Abschnitt 2.4.) Auf der Grundlage der getätigten Überlegungen werden im Abschnitt 3 die durchgeführten Experimente sowie deren Ergebnisse vorgestellt. Als potentiell katalytisch wirksamer Komplex wurde der Kupfer(I)-Komplex Rac. [σ(N):σ(P)-(1-N,N-Dimethylaminomethyl-2-P,P-diphenylphosphinoferrocen)(triphenylphosphin)(acetonitril) kupfer(I)]-tetrafluoroborat 4A hergestellt. Seine Struktur konnte sowohl mittels NMR-Spektroskopie als auch Röntgeneinkristallstrukturanalyse aufgeklärt werden.

Techn. Universiẗat, Diss., 2006--Darmstadt.

Dissertação (mestrado)—Univerdidade de Brasília, Instituto de Química, 2010. / Submitted by Allan Magalhães (allanout@gmail.com) on 2011-07-01T02:23:38Z No. of bitstreams: 1 2010_AdolfoCarlosBarrosdeSouza.pdf: 9747307 bytes, checksum: f86299bd6df2dfa4da7577de17030749 (MD5) / Approved for entry into archive by Guilherme Lourenço Machado(gui.admin@gmail.com) on 2011-07-14T12:45:45Z (GMT) No. of bitstreams: 1 2010_AdolfoCarlosBarrosdeSouza.pdf: 9747307 bytes, checksum: f86299bd6df2dfa4da7577de17030749 (MD5) / Made available in DSpace on 2011-07-14T12:45:45Z (GMT). No. of bitstreams: 1 2010_AdolfoCarlosBarrosdeSouza.pdf: 9747307 bytes, checksum: f86299bd6df2dfa4da7577de17030749 (MD5) / O centro quinônico foi utilizado para a preparação de aminonaftoquinonas alifáticas na tentativa de aplicar essa classe de moléculas na reação multicomponente do tipo Hantszch. Após a caracterização por RMN de 1H e 13C dos compostos sintetizados, a partir da adição nucleofílica das aminas na bromonaftoquinona, observou-se que houve a formação de dois compostos no meio reacional, o principal, 85a-j e secundário, 86a-j (82-71% e 18-10%, respectivamente). Estudos quântico-teóricos foram realizados a fim de explicar a formação do produto principal. Os resultados mostraram que a reação de adição de Michael das aminas está relacionada com o caráter eletrostático entre o carbono ligado ao bromo, descartando assim, a hipótese de que a reação é regida por orbitais de fronteira. Foram realizadas várias tentativas para sintetizar o composto proveniente da reação multicomponente de Hantszch, porém apenas a matéria prima foi isolada. Outro estudo quânticoteórico foi realizado no intuito de explicar o porquê que a reação não tinha ocorrido. Com os resultados obtidos, concluiu-se que havia uma grande diferença entre as energias dos orbitais de fronteira dos reagentes. Sendo assim, vislumbrou-se como solução reduzir o sistema quinônico para, em seguida, realizar a reação multicomponente de Hantzsch. Várias tentativas foram feitas a fim de reduzir o sistema aminonaftoquinônico, porém nenhuma delas gerou o produto desejado. Na tentativa de preparar as aminonaftoquinonas no estado reduzido, realizou-se o acoplamento de Ullmann em sistemas bromonaftoquinônicos reduzidos, com diferentes grupos protetores com a finalidade de acoplar diferentes aminas. Apesar de não obter o produto desejado, os resultados se mostraram promissores, pois a formação do subproduto 134 garante que o intermediário organocuprato da reação foi formado. Também foi realizada a reação de Sonogashira no intuito de gerar compostos do tipo pirroloquinônicos. O produto desejado não foi isolado devido à dificuldade que se teve em preparar a amida 182. Como o par de elétrons da amina encontra-se espalhado no sistema quinônico, este não é nucleofílico suficiente para atacar o cloreto de acetila 185. _________________________________________________________________________________ ABSTRACT / Bromonaphtoquinone was used to prepare a variety of aliphatic aminonaphthoquinones in order to apply to this molecular class the Hantzch multicomponent reaction (MCR). Upon the nucleophilic addition of amines and amino esters to bromonaphthoquinones, two compounds were formed, the major 85a-j and the minor 86a-j, in 82-71% and 10-18% of yields, respectively. The formation of the minority compound 86a-j was confirmed upon characterization of all isolated compounds by 1H and 13C NMR. Quantumtheoretical calculations were performed to explain the formation of the major product. The results showed that the Michael addition reaction of amines to this system is related to the electrostatic effects of the carbon atom binding to bromine, while the hypothesis that the reaction is governed by frontier orbitals could be discarded. Several attempts were made to synthesize the expected compounds by applying the Hantzsch multicomponent reaction to the produced amines, but only starting materials were isolated. Another quantum-theoretical study was conducted in order to explain why the reaction had not occurred. From these results, we concluded that there was a large difference between the energies of the frontier orbitals of the reactants. This result led to the hypothesis that perhaps upon reduction of the naphthoquinone system, the Hantzch reaction might take place. Several attempts were made to reduce the aminonaphthoquinonic system, but none generated the desired dihydroproduct. In an attempt to prepare the desired amino compounds by Ullmann coupling of bromonaphthohydroquinones, several hydroxy protecting groups were prepared. Despite the examination of several reaction conditions, the desired amino compounds were not isolated. However, the results of this reaction were promising, because the formation of byproduct 134 ensures that the intermediary organocuprate was generated in situ. We also carried out a Sonogashira coupling reaction with the goal to generate compounds of the pyrrolonaphtoquinonic type. Once more, the desired product was not isolated, due to difficulties we had in preparing amide 182. One explanation for this may be due to the lone pair of electrons of the amine being spread over the naphthoquinone π system, decreasing drastically the nucleophilicity of the amine in attacking acetyl chloride 185.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-08-04T13:56:59Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Tese de doutorado - Mauro Gomes..pdf: 11151423 bytes, checksum: 8078c54c11b179c8f72bccc64042575f (MD5) / Made available in DSpace on 2017-08-04T13:56:59Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Tese de doutorado - Mauro Gomes..pdf: 11151423 bytes, checksum: 8078c54c11b179c8f72bccc64042575f (MD5) Previous issue date: 2016-08-26 / CAPES / Utilizando a estratégia de hibridação molecular, neste trabalho foi construído uma quimioteca de heterocíclicos furânicos, triazólicos e quinolínicos contendo o núcleo naftoquinona, reunindo características estruturais de compostos bioativos distintos, originando assim, moléculas híbridas com amplo potencial farmacológico. Inicialmente, foram sintetizados seis derivados 2-acetoxi-3-alquinill-1,4naftoquinonas via reação de acoplamento Sonogashira entre o 2-acetoxi-3-iodo-1,4naftoquinona e diversos alquinos terminais funcionalizados com rendimentos que variaram de 40-73%, que posteriormente foram submetidos a uma heterocilização intramolecular, formando os derivados furanonaftoquinonas com rendimentos bons entre 72-85%. Os derivados 2-acetoxi-3-alquinil-1,4-naftoquinonas e os furanonaftoquinonas foram submetidos à avaliação do potencial citotóxico em três linhagens de células de glioblastomas, GBMO2, GBM95 e A172, apresentando, no geral, resultados satisfatórios para inibição do crescimento celular. Os compostos 2acetoxi-3-feniletinil-1,4-naftoquinona, 2-acetoxi-3-(4-metoxilfeniletinil)-1,4naftoquinona e 2-acetoxi-3-(4-metilfeniletinil)-1,4-naftoquinona se destacaram dentre as substâncias analisadas por apresentarem menor CI50 para as três linhagens celulares de glioblastomas testadas, resultados estes significativos para dar continuidade nos estudos de citotoxicidade. Em seguida, foi desenvolvida uma nova rota sintética para obtenção por “click chemistry” de novos compostos aminoalquiltriazóis naftoquinônicos através das reações de cicloadição 1,3-dipolar entre 2azidoalquilamino-1,4-naftoquinonas e diversos alquinos terminais, sendo sintetizados vinte novos derivados 2-[(1H-1,2,3-triazol-1-il)alquilamino]-1,4naftoquinonas com rendimentos entre 70-97%. Estes heterocíclicos triazólicos foram avaliados frente às linhagens tumorais HEp-2 (carcinoma de laringe humana), NCIH292 (carcinoma mucoepidermoide de pulmão humano), HT-29 (adenocarcinoma de colón humano), MCF-7 (câncer de mama humano) e HL-60 (leucemia promielocitica aguda). Os compostos 2-[2-(4-propil-1H-1,2,3-triazol-1-il)etilamino]-1,4-naftoquinona e 2-{3-[4-(2-hidroxibutan-2-il)-1H-1,2,3-triazol-1-il]propilamino}-1,4-naftoquinona exibiram citotoxicidade moderada frente às linhagens HL-60, HL-60 e MCF-7, respectivamente, demonstrando ação inibitória seletiva. Por fim, foram sintetizados vinte quatro derivados 6-alquilamino-5,8-quinolinoquinonas a partir de uma direta aminação nucleofílica do 7-bromo-5,8-quinolinoquinona com aminas primárias e secundárias, sendo desenvolvida uma nova estratégia sintética para a obtenção dos compostos 6-alquilamino-5,8-quinolinoquinonas a partir de aminas primárias. Estes compostos são promissores candidatos para desenvolvimento de novas drogas antitumorais. / By using the strategy of molecular hybridization, in this work it was built a chemical library with furan, triazole and quinoline heterocyclic compounds, containing the naphthoquinone nucleus, gathering structural characteristics of distinct bioactives resulting in hybrid molecules with large pharmacological potencial. Initially, six 2acetoxy-3-alkynyl-1,4-naphthoquinone derivatives were synthesized through Sonogashira cross coupling reaction involving 2-acetoxy-3-iodo-1,4-naphthoquinone and several functionalized terminal alkynes in 40-73% yields, which later were submitted to intramolecular heterocyclization, forming the furan derivatives in 72-85% yields. The 2-acetoxy-3-alkynyl-1,4-naphthoquinone and furanonaphthoquinone derivatives were submitted to cytotoxic screening against three glioblastoma cell lines GBMO2, GBM95 e A172, resulting in satisfactory results to the inhibition of cellular growth. The 2-acetoxy-3-phenylethynyl-1,4-naphthoquinone, 2-acetoxy-3-(4methoxyphenylethynyl)-1,4-naphthoquinone and 2-acetoxy-3-(4methylphenylethynyl)-1,4-naphthoquinone stood out among the substances analyzed by their lower IC50 for the three cell lines tested glioblastomas. These results are significant to continue in the cytotoxicity studies. Then, a new synthetic route by “click chemistry” was developed to obtain new aminoalkyl-triazoles naphthoquinone compounds through the reactions of 1,3-dipolar cycloaddition between 2azidoalkylamino-1,4-napthoquinones and several terminal alkynes. A serie of twenty 2-[(1H-1,2,3-triazole-1-yl)alkylamino]-1,4-naphthoquinones derivatives were synthetized in 70-97% yields. These triazole heterocyclics were tested against the tumor cell lines HEp-2 (human laryngeal carcinoma), NCI-H292 (human mucoepidermoid lung carcinoma), HT-29 (human colon adenocarcinoma), MCF-7 (human breast cancer) and HL-60 (human promyelocytic leukemia). The compounds 2-[2-(4-propyl-1H-1,2,3-triazole-1-yl)ethylamino]-1,4-naphthoquinone and 2-{3-[4-(2hydroxybut-2-yl)-1H-1,2,3-triazole-1-yl]propylamino}-1,4-naphthoquinone showed moderated cytotoxicity against HL-60, HL-60 e MCF-7, showing a selective inhibition profile. Finally, twenty four 6-alkylamino-5,8-quinolinequinones were obtained by direct nucleophilic amination of 7-bromo-5,8-quinolinequinone with primary and secondary alkylamines, providing a new synthetic strategy to the acquisition of 6alkylamino-5,8-quinolinequinones compounds from primary amines. These compounds are promising candidates for the development of new antitumor drugs.

>Magister Scientiae - MSc / Due to the negative impact on the environment and the associated biological risks on human and animal life, the need for eco-friendly synthetic protocols is critical. With the rapid advancement in nanotechnology, this extends to the synthesis of nanomaterials. Eco-friendly nanoparticle synthesis protocols have led to the use of fungi, plants and other biological substances, due to their remarkable ability in reducing metal ions. This led to the formation of very efficient hybrid catalysts, which are partially organic/inorganic composites. Palladium nanoparticles have drawn much interest due to its potential in catalytic applications and in photovoltaic cell development. In this study, the brown marine algae, Ecklonia radiata, was employed as a putative palladium nanoparticle bioreactor. Aqueous extracts of the algae were used as a supporting matrix for the synthesis of palladium nanoparticle (AE-PdNPs) catalysts according to the principles of green chemistry. The catalysts were then assessed for their capability in various carbon-carbon coupling reactions such as Suzuki-Miyaura, Sonogashira, and Heck coupling reactions. Selectivity studies were also performed. The PdNPs were compared to “model” polyvinylpyrrolidone palladium nanoparticles (PVP-PdNPs), synthesized according to literature methods. A variety of spectroscopic techniques were used to characterize the nanoparticles and the organic reaction products, including HRTEM, EDX, NMR, FTIR, DLS, TGA, UV-Vis, ICP-AES, GC-MS and XRD spectroscopy. qNMR was used to determine the product % yields. The aqueous extracts were characterised using NMR and a variety of assays, including total antioxidant potential, total reducing power and radical scavenging ability) to assess its ability to reduce the Pd metal salt. 2D NMR revealed polysaccharides and polyphenols to be the major and minor components, respectively, present in the extract. HRTEM images revealed the average size of the AE-PdNPs and PVP-PdNPs to be 12 nm and 8 nm, respectively. The images also showed the shapes of the NPs to be cubic for the AE-PdNPs and cubic or triangular for the PVP-PdNPs. SAED and XRD spectroscopy revealed the face-centred cubic phase and polycrystalline nature of the AE-PdNPs. No reliable data, other than the HRTEM images was obtained for the PVP-PdNPs. Zeta potential and DLS measurements confirmed the negative charge present on the surface of the nanoparticles, while the hydrodynamic radii were found to be 65 nm and 99 nm for the AE- and PVP-PdNPs, respectively, substantiating the presence of the capping agents. ICP-AES analysis revealed the Pd content of the NPs to be 48.8 and 28.9 ppm for the AE- and PVP-PdNPs. Following characterization, the PdNPs were assessed as potential catalysts in the Suzuki-Miyaura, Heck and Sonogashira carbon-carbon coupling reactions. Bromo and iodo substrates were employed, together with sterically hindered substrates, with a nitro moiety in the ortho or para positions. For the Suzuki-Miyaura reactions, both sets of PdNPs revealed slightly higher yields for the products synthesized using the bromo substrate (>90%), while low yields (40 – 55% yields) were obtained for the ortho substituted substrate in comparison to the para substrate (>90% yields). The Heck coupling reactions with butyl acrylate and 4-iodoacetphenone were successful (~70% yields), while reactions with 4-bromoacetophenone failed. However, the Sonogashira couplings did not proceed at all. With the series of reactions NPs showed some selectivity, with the AE-PdNPs consistently producing higher yields for the products obtained. This may be due to overall nature of the NPs, or due to the higher platinum loading content for the AE-PdNPs.

Significant attention from the medicinal and pharmaceutical communities has been pushed towards the design and development of natural products for defence against many forms of illnesses. The Amaryllidaceae plant family has shown their prevalence over time aiding towards our needs and becoming viable sources of alkaloids due to their wide variety of bioactivities presented. The low availability towards these often-complex structures with at times comprising up to six contiguous chiral centers have made practical testing scarce. More dominantly the isocarbostyrils are well recognized, being hydroxylated phenanthridones providing increased activities making them model targets to test and develop new synthetic strategies towards. These compounds represent a subset of the Amaryllidaceae alkaloids that lack a basic nitrogen center. This thesis describes the total synthesis of four derivatives of the antiviral natural product (+)-trans-dihydronarciclasine from α-azidoacetone and m-anisaldehyde. Herein we demonstrate constructive routes towards ring-A modified, fully functionalized rings-B/C derivatives synthesized via asymmetric chemical syntheses providing further insight into SAR studies. This thesis expands on the organocatalytic [3+3]-cycloaddition sequence to produce aminocyclitol cores providing effective routes towards the development of five stereogenic centers in all targeted ring-C structures. Such studies were attributed to the enal adducts isolated from the Wittig reaction towards four natural product derivatives gaining knowledge related to the targeted molecules mode of action. One additional (+)-transdihydrolycoricidine analogue will be communicated, that enables the imaging while inside live cells with use of alkyne-tag Raman imaging. Limitations of the alkaloids include the toxicity that accompanies these agents and the poor aqueous solubilities they provide, eliciting an increased need for new antiviral agents. The syntheses communicated provide effective routes towards unnatural alkaloids and can be pushed towards alternative chiral aminocyclitol targets for future studies. All compounds have been sent away for screening including against coronavirus at Johns Hopkins. / Thesis / Bachelor of Science (BSc) / This thesis is primarily driven towards the development of four antiviral lycorane structural type alkaloids, and an analogue synthesized via a copper-cocatalyzed Sonogashira reaction, utilizing a labile phenol-derived sulfonated hydroxyl group in its coupling towards an alkyne tagged structure. This method provides easy access for a variety of compounds without a fluorescent tag, taking steps forward in elucidating how the Amaryllidaceae alkaloids are delivering their biological effects. The densely substituted ring-C was obtained via an asymmetric organocatalytic [3+3] sequence for the assembly of the aminocyclitol core and is described. This sequence has provided effective regio, diastereo, and enantioselective access to five unnatural products. Preparation of the precursors were prepared using a Wittig methodology previous reported by the McNulty group that has been used in many syntheses for various Amaryllidaceae alkaloids