Orientadores: Luiz Carlos Dias, Jean-Marc Campagne / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-26T12:59:10Z (GMT). No. of bitstreams: 1 Sant'ana_DaniloPereirade_D.pdf: 12186591 bytes, checksum: 82263f5c920d42c10acf04cf823af93f (MD5) Previous issue date: 2014 / Resumo: SÍNTESE DO FRAGMENTO C1-C9 DA (-)-DICTIOSTATINA: A (-)-dictiostatina é uma macrolactona de origem marinha que apresenta uma potente atividade antitumoral, inibindo a proliferação de células cancerígenas em concentrações na ordem de nanomolar. Propusemos desenvolver uma nova rota sintética para o fragmento C1-C9 deste produto natural. Conseguimos sintetizar o fragmento C1-C9 da (-)-dictiostatina em 15 etapas a partir do 1,3-propanodiol com 3,57% de rendimento global. Nossa rota sintética utilizou como etapas chaves a epoxidação assimétrica de Sharpless e a abertura de epóxido nas condições de Myashita para formar os centros estereogênicos. Este fragmento compreende os carbonos C1-C9 da (-)-dictiostatina, no qual está contido o dieno 2Z,4E e dois centros estereogênicos (C6R, C7S do produto natural). ESTUDOS VISANDO A SÍNTESE TOTAL DA (+)-TAUTOMICETINA: A (+)-tautomicetina é um policetídeo natural isolado em 1989 a partir de Streptomyces griseochromogenes como um antifúngico. Atualmente, TTN é mais conhecida pela sua atividade em proteínas serina/treonina fosfatases. Propusemos desenvolver uma rota sintética convergente para este produto natural. Conseguimos sintetizar dois fragmentos da tautomicetina, sendo o fragmento B2 correspondendo a parte C1-C12 e o composto 260 que consiste na parte C7¿-C13 da (+)-tautomiceina. A síntese do fragmento B2 teve como etapa chave a abertura estereosseletiva de epóxido quiral, o que consiste uma estratégia inédita para construir a parte desoxipropionato da TTN. A síntese do composto 260 teve como etapa chave, uma metodologia inédita de bis-esterificação de anidridos desenvolvida em nosso grupo de pesquisa / Abstract: SYNTHESIS OF THE C1-C9 FRAGMENT OF (-)-DICTYOSTATIN: (-)-Dictyostatin is a marine macrolactone with potent antitumor activity. Herein, we report the development of a new synthetic route for the C1-C9 fragment of this natural product. The C1-C9 fragment of (-)-dictyostatin was synthesized in 15 steps and 3.57% overall yield from 1,3-propanediol. Our synthetic route employed Sharpless asymmetric epoxidation and epoxide opening under Myashita's conditions as key steps to form the stereogenic centers. The C1-C9 fragment contains the 2Z,4E diene and two stereogenic centers (C6R, C7S) contained in the natural product. STUDIES TOWARD THE TOTAL SYNTHESIS OF (+)-TAUTOMYCETIN: (+)-Tautomycetin is a polyketide natural product isolated in 1989 from Streptomyces griseochromogenes with antifungal activity. Currently, TTN is best known for its activity in serine/threonine phosphatase proteins. We developed a convergent synthetic route to this natural product. Two key fragments of (+)-tautomycetin were synthesized, the B2 fragment containing the C1-C12 chain and the compound 260, corresponding to the C7'-C13 fragment of (+)-tautomycetin. The synthesis of fragment B2 employed a stereoselective chiral epoxide opening reaction as a key step, which consist of a novel strategy to prepare the desoxypropionate moiety of TTN. The synthesis of 260 employed a novel method for bis-esterification of anhydrides developed in the Dias-Campagne groups / Doutorado / Quimica Organica / Doutor em Ciências

Le motif SCF3 a suscité l'engouement de la communauté scientifique du fait de ses propriétés remarquables, dont sa capacité à augmenter la lipophilie des molécules le portant. Dans ce contexte, le développement de méthodes innovantes permettant son introduction directe sur divers substrats nous est apparu pertinent. Cette thèse traite premièrement de la proposition d'un réactif de trifluorométhylthiolation électrophile inédit, CF3SO2Cl. Il a aussi été démontré que par modulation des conditions opératoires, CF3SO2Cl pouvait jouer le rôle de source de SOCF3 électrophile. Deuxièmement, deux voies novatrices de synthèse novatrices permettant l'accès à des molécules SCF3 d'intérêt ont été élaborées: la trifluorométhylthiolation nucléophile de sulfamidates cycliques, pour l'obtention d'amines et d'acides aminés ω-SCF3 chiraux, et la trifluorométhylthiolation diastéréosélective électrophile d'oxazolidinones, pour la préparation d'alcools β-SCF3 énantiopurs ou d'acides α-SCF3 énantioenrichis. / The SCF3 moiety has recently raised the interest of the scientific community thanks to its remarkable properties, among which its ability to increase the lipophilicity of the molecules featuring it. In this context, developing innovative methodologies allowing its direct introduction onto various substrates appeared particularly relevant to us. Consequently, this PhD thesis first deals with the proposition of a new electrophilic trifluoromethylthiolation reagent, CF3SO2Cl. It was also proved that, by tuning the reaction conditions, CF3SO2Cl could also serve as a source of the SOCF3 motif. Secondly, two synthetic pathways allowing the isolation of interesting SCF3 species were elaborated: the nucleophilic trifluoromethylthiolation of cyclic sulfamidates for the generation of chiral ω-SCF3 amines and amino acids, and the diastereoselective electrophilic trifluoromethylthiolation of oxazolidinones for the preparation of enantiopure β-SCF3 alcohols and enantioenriched α-SCF3 acids.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18814号 / 理博第4072号 / 新制||理||1586(附属図書館) / 31765 / 京都大学大学院理学研究科化学専攻 / (主査)教授 丸岡 啓二, 教授 大須賀 篤弘, 教授 時任 宣博 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19014号 / 工博第4056号 / 新制||工||1624(附属図書館) / 31965 / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 杉野目 道紀, 教授 澤本 光男, 教授 辻 康之 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第19660号 / 薬科博第48号 / 新制||薬科||6(附属図書館) / 32696 / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 川端 猛夫, 教授 高須 清誠, 教授 竹本 佳司 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20947号 / 理博第4399号 / 新制||理||1632(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 丸岡 啓二, 教授 依光 英樹, 教授 大須賀 篤弘 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

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京都大学 / 新制・課程博士 / 博士(理学) / 甲第23736号 / 理博第4826号 / 新制||理||1690(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 杉山 弘, 教授 深井 周也, 教授 秋山 芳展 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

Two organic synthetic methods for the generation of methyl bearing chiral centers have been developed using: 1) dimerization of methylketene and 2) a free radical-based addition/elimination reaction involving allyl bromides. The first method, the asymmetric dimerization of methyl ketene, followed by an asymmetric aldol reaction and the appropriate functional group manipulations enabled us to construct the (2S, 4S, 6S) trimethylnonyl subunit found in the siphonariene class of natural products. The latter method explored the stereoselective potential of a free radical-based condensation reaction by examining compounds which are known to be able to support chiral auxiliaries and chiral Lewis acids. Additionally, substituent effect on the rates of this reaction were examined closely and found to be comparable to similar, previously examined systems. The synthetic utility, magnitude and scope of this reaction are discussed. / Ph. D.