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Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-06-02T18:27:27Z No. of bitstreams: 1 fabiodesouzafernandes.pdf: 7715864 bytes, checksum: acdec01f503078f8065c0a21a2cabf58 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-07-02T13:17:43Z (GMT) No. of bitstreams: 1 fabiodesouzafernandes.pdf: 7715864 bytes, checksum: acdec01f503078f8065c0a21a2cabf58 (MD5) / Made available in DSpace on 2016-07-02T13:17:43Z (GMT). No. of bitstreams: 1 fabiodesouzafernandes.pdf: 7715864 bytes, checksum: acdec01f503078f8065c0a21a2cabf58 (MD5) Previous issue date: 2012-02-27 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As aminas e aminoalcoóis são uma importante classe química que se encontra presente em um vasto grupo de substâncias de ocorrência natural e sintética. O aminoálcool S,S-etambutol é um agente quimioterapêutico antitubercular seguro de primeira escolha. Aminas e aminoalcoóis glicosilados são conhecidos pelas suas atividades antibacterianas. Este trabalho trata da síntese de derivados de aminoalcoóis acoplados a série D-arabinose e D-galactose, que resultou na obtenção de quatorze compostos inéditos. Em um primeiro momento foram preparados seis diaminas e sete aminoálcoois N-alquilados com cadeias carbônicas de diferentes tamanhos. As diaminas e aminoalcoóis obtidos foram acoplados ao intermediário 6-O-(2’,3’- epoxipropil)-1,2:3,4-di-isopropilideno- -D-galactopiranosídeo que foi preparado por meio de reações clássicas da química de carboidratos. Foram obtidos treze compostos inéditos estando todos na forma de mistura de diasteroisômeros. Obteve-se também um aminoálcool derivado da série D-arabinose. Este foi preparado pela reação de abertura do epóxido do derivado 2,3-anidro-5-Obenzil- -D-lixofuranosídeo de metila pelo aminoálcool comercial monoetanolamina. Vários aminoálcoois da série D-galactose, foram submetidos à avaliação de suas atividades antibacterianas e antituberculose e apresentaram resultados promissores. / A amines and aminoalcohols are important chemical classes that are present in a large group of synthetic and naturally occurring substances. The presence of alcohol and amine functional groups allow these substances aminoalcohol S,S-ethambutol is a reliable first-line antitubercular chemotherapeutic agent. Glycosylated amines and aminoalcohols are known for their antibacterial activities. This work describes the synthesis of aminoalcohols derived from Darabinose and D-galactose which resulted in the synthesis of fourteen novel compounds. Initially we reported the preparation of six diamines and seven Nalkylated amines with carbon chains of different lengths. The diamines and aminoalcohols thus obtained were coupled to the intermediate 6-O-(2’,3’- epoxypropyl)-1,2:3,4-di-isopropylidene- -D-galactopyranoside that was prepared by classical carbohydrate chemical reactions. Thirteen new compounds were obtained, all in the form of diastereoisomeric mixture. We also obtained an aminoalcohol derived from D-arabinose series. This was prepared by the epóxido opening reaction of methyl 2,3-anydro-5-Obenzyl- -D-lyxofuranoside from the commercial aminoalcohol monoethanolamine. Several aminoalcohols of the D-galactose series were submitted for biological assays in order to evaluate their antibacterial and antitubercular activities and showed promising results.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-06-28T19:17:55Z No. of bitstreams: 1 fabiodesouzafernandes.pdf: 7715864 bytes, checksum: acdec01f503078f8065c0a21a2cabf58 (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-07-05T14:33:16Z (GMT) No. of bitstreams: 1 fabiodesouzafernandes.pdf: 7715864 bytes, checksum: acdec01f503078f8065c0a21a2cabf58 (MD5) / Made available in DSpace on 2016-07-05T14:33:16Z (GMT). No. of bitstreams: 1 fabiodesouzafernandes.pdf: 7715864 bytes, checksum: acdec01f503078f8065c0a21a2cabf58 (MD5) Previous issue date: 2012-02-27 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As aminas e aminoalcoóis são uma importante classe química que se encontra presente em um vasto grupo de substâncias de ocorrência natural e sintética. O aminoálcool S,S-etambutol é um agente quimioterapêutico antitubercular seguro de primeira escolha. Aminas e aminoalcoóis glicosilados são conhecidos pelas suas atividades antibacterianas. Este trabalho trata da síntese de derivados de aminoalcoóis acoplados a série D-arabinose e D-galactose, que resultou na obtenção de quatorze compostos inéditos. Em um primeiro momento foram preparados seis diaminas e sete aminoálcoois N-alquilados com cadeias carbônicas de diferentes tamanhos. As diaminas e aminoalcoóis obtidos foram acoplados ao intermediário 6-O-(2’,3’- epoxipropil)-1,2:3,4-di-isopropilideno- -D-galactopiranosídeo que foi preparado por meio de reações clássicas da química de carboidratos. Foram obtidos treze compostos inéditos estando todos na forma de mistura de diasteroisômeros. Obteve-se também um aminoálcool derivado da série D-arabinose. Este foi preparado pela reação de abertura do epóxido do derivado 2,3-anidro-5-Obenzil- -D-lixofuranosídeo de metila pelo aminoálcool comercial monoetanolamina. Vários aminoálcoois da série D-galactose, foram submetidos à avaliação de suas atividades antibacterianas e antituberculose e apresentaram resultados promissores. / A amines and aminoalcohols are important chemical classes that are present in a large group of synthetic and naturally occurring substances. The presence of alcohol and amine functional groups allow these substances aminoalcohol S,S-ethambutol is a reliable first-line antitubercular chemotherapeutic agent. Glycosylated amines and aminoalcohols are known for their antibacterial activities. This work describes the synthesis of aminoalcohols derived from Darabinose and D-galactose which resulted in the synthesis of fourteen novel compounds. Initially we reported the preparation of six diamines and seven Nalkylated amines with carbon chains of different lengths. The diamines and aminoalcohols thus obtained were coupled to the intermediate 6-O-(2’,3’- epoxypropyl)-1,2:3,4-di-isopropylidene- -D-galactopyranoside that was prepared by classical carbohydrate chemical reactions. Thirteen new compounds were obtained, all in the form of diastereoisomeric mixture. We also obtained an aminoalcohol derived from D-arabinose series. This was prepared by the epóxido opening reaction of methyl 2,3-anydro-5-Obenzyl- -D-lyxofuranoside from the commercial aminoalcohol monoethanolamine. Several aminoalcohols of the D-galactose series were submitted for biological assays in order to evaluate their antibacterial and antitubercular activities and showed promising results.

Quando o tetrafluoroborato de N-(α-carbometoximetil)-2,4,6-trifenilpiridínio (Ia) foi tratado com hidróxido de potássio em etanol, resultou uma betaína que, ao ser aquecida na presença de benzaldeído ou p-clorobenzaldeído, não produziu a esperada oxazolidina IIa. Em lugar desta 1,2-di-hidropiridina, formou-se um sal cujo cátion correspondia à estrutura de um N-metil-2,4,6-trifenilpiridínio (III). Este composto resultaria da protonação da ilida intermediária, formada pela descarboxilação da betaína. Porém, quando o mesmo tipo de reação foi efetuada com o derivado α-metilado Ib, o espectro de RMN de H do produto bruto indicou a formação da di-hidropiridina (IIb), na forma de 4 estereoisômeros. A oxazolidina IIa, como um isômero largamente majoritário, pôde ser obtida pela reação do tetrafluoroborato de N-metil-2,4,6-trifenilpiridínio (III) com p-clorobenzaldeído, na presença de uma solução diluída de álcali. Esta oxazolidina era bastante instável e não pode ser purificada, sendo submetida na forma bruta à reação de Diels-Alder com a N-metil-maleimida. Esta reação conduziu a dois adutos isoméricos (IV e V). Embora o aduto majoritário (V) fosse estável em solução de deutero-clorofórmio, o aduto minoritário (IV), na presença desse solvente e à temperatura ambiente, isomerizava-se após algumas horas. A estrutura dos três adutos foi determinada por experimentos de RMN de H (NOESY e NOE 1D seletivo). A adição de um pequeno volume de solução diluída de ácido clorídrico aos compostos IV e V, dissolvidos em acetonitrila e à temperatura ambiente, resultou na isomerização catalítica desses adutos. Porém, quando esta reação de protonação foi efetuada sob refluxo de acetonitrila, formaram-se dois produtos (VI e VII), cuja estrutura era compatível com ocorrência de uma reação de retro-aza Diels-Alder. Finalmente, foi estudado o equilíbrio conformacional de dois novos sais de 2,4,6-trifenil- piridínio, e os resultados foram comparados com aqueles obtidos para os sais análogos 2,4,6-trimetil-substituídos. / When the tetrafluoroborate of N-(α-carbomethoxymethyl)-2,4,6-triphenylpridinium (Ia) was submitted to alkaline hydrolysis followed by decarboxylation upon heating, the resulting betaine failed to undergo the aldol addition reaction with aromatic aldehydes leading, in lieu of the expected oxazolidine (IIa),a salt bearing the cation N-methyl-2,4,6-triphenylpyridinium (III), as a result of the easy protonation of the intermediate ylide. However, for the corresponding a-methylated salt (Ib), the formation of four stereoisomeric 1,2- dihydropiridines was confirmed by inspection of the H NMR of the crude product. As an alternative to this method for obtaining IIa, a mixture of III and p-chlorobenzaldehyde was stirred at room temperature for several hours, in the presence of a diluted aqueous alkali. The resulting 1,2-dihidropyridine (IIa) was rather unstable precluding its isolation from the crude product mixture, and was submitted, without further purification, to the Diels-Alder reaction with Nmethylmaleimide, leading to two diastereomeric isoquinuclidines (IV) and (V). Although the major isomer showed to be stable in a deuterochloroform solution, the minor isomer (IV) underwent a spontaneous isomerization, upon standing in such solvent at room temperature. The stereochemical features of these three aducts could be accessed by NOESY and 1D NOE selective H NMR experiments. By treating a solution of adducts IV and V in acetonitrile with a small volume of aqueous HCl, at room temperature, an acid catalyzed isomerization took place. However, when the protonation reaction of the major diastereoisomer (V) was performed in acetonitrile at the reflux temperature, two products (VI and VII) were isolated, highlighting the occurrence of a retro-aza Diels Alder reaction. Finally, the conformation equilibria for two new 2,4,6-triphenyl- pyridinium salts was investigated. Results were correlated with previous ones referring to analogous 2,4,6-trimethyl- salts.

Quando o tetrafluoroborato de N-(α-carbometoximetil)-2,4,6-trifenilpiridínio (Ia) foi tratado com hidróxido de potássio em etanol, resultou uma betaína que, ao ser aquecida na presença de benzaldeído ou p-clorobenzaldeído, não produziu a esperada oxazolidina IIa. Em lugar desta 1,2-di-hidropiridina, formou-se um sal cujo cátion correspondia à estrutura de um N-metil-2,4,6-trifenilpiridínio (III). Este composto resultaria da protonação da ilida intermediária, formada pela descarboxilação da betaína. Porém, quando o mesmo tipo de reação foi efetuada com o derivado α-metilado Ib, o espectro de RMN de H do produto bruto indicou a formação da di-hidropiridina (IIb), na forma de 4 estereoisômeros. A oxazolidina IIa, como um isômero largamente majoritário, pôde ser obtida pela reação do tetrafluoroborato de N-metil-2,4,6-trifenilpiridínio (III) com p-clorobenzaldeído, na presença de uma solução diluída de álcali. Esta oxazolidina era bastante instável e não pode ser purificada, sendo submetida na forma bruta à reação de Diels-Alder com a N-metil-maleimida. Esta reação conduziu a dois adutos isoméricos (IV e V). Embora o aduto majoritário (V) fosse estável em solução de deutero-clorofórmio, o aduto minoritário (IV), na presença desse solvente e à temperatura ambiente, isomerizava-se após algumas horas. A estrutura dos três adutos foi determinada por experimentos de RMN de H (NOESY e NOE 1D seletivo). A adição de um pequeno volume de solução diluída de ácido clorídrico aos compostos IV e V, dissolvidos em acetonitrila e à temperatura ambiente, resultou na isomerização catalítica desses adutos. Porém, quando esta reação de protonação foi efetuada sob refluxo de acetonitrila, formaram-se dois produtos (VI e VII), cuja estrutura era compatível com ocorrência de uma reação de retro-aza Diels-Alder. Finalmente, foi estudado o equilíbrio conformacional de dois novos sais de 2,4,6-trifenil- piridínio, e os resultados foram comparados com aqueles obtidos para os sais análogos 2,4,6-trimetil-substituídos. / When the tetrafluoroborate of N-(α-carbomethoxymethyl)-2,4,6-triphenylpridinium (Ia) was submitted to alkaline hydrolysis followed by decarboxylation upon heating, the resulting betaine failed to undergo the aldol addition reaction with aromatic aldehydes leading, in lieu of the expected oxazolidine (IIa),a salt bearing the cation N-methyl-2,4,6-triphenylpyridinium (III), as a result of the easy protonation of the intermediate ylide. However, for the corresponding a-methylated salt (Ib), the formation of four stereoisomeric 1,2- dihydropiridines was confirmed by inspection of the H NMR of the crude product. As an alternative to this method for obtaining IIa, a mixture of III and p-chlorobenzaldehyde was stirred at room temperature for several hours, in the presence of a diluted aqueous alkali. The resulting 1,2-dihidropyridine (IIa) was rather unstable precluding its isolation from the crude product mixture, and was submitted, without further purification, to the Diels-Alder reaction with Nmethylmaleimide, leading to two diastereomeric isoquinuclidines (IV) and (V). Although the major isomer showed to be stable in a deuterochloroform solution, the minor isomer (IV) underwent a spontaneous isomerization, upon standing in such solvent at room temperature. The stereochemical features of these three aducts could be accessed by NOESY and 1D NOE selective H NMR experiments. By treating a solution of adducts IV and V in acetonitrile with a small volume of aqueous HCl, at room temperature, an acid catalyzed isomerization took place. However, when the protonation reaction of the major diastereoisomer (V) was performed in acetonitrile at the reflux temperature, two products (VI and VII) were isolated, highlighting the occurrence of a retro-aza Diels Alder reaction. Finally, the conformation equilibria for two new 2,4,6-triphenyl- pyridinium salts was investigated. Results were correlated with previous ones referring to analogous 2,4,6-trimethyl- salts.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-11-01T13:49:43Z No. of bitstreams: 1 elainedefreitascastroreis.pdf: 3548670 bytes, checksum: 46c9a924e7e08aa3c3e9f25546e3d941 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-12-15T13:24:30Z (GMT) No. of bitstreams: 1 elainedefreitascastroreis.pdf: 3548670 bytes, checksum: 46c9a924e7e08aa3c3e9f25546e3d941 (MD5) / Made available in DSpace on 2016-12-15T13:24:30Z (GMT). No. of bitstreams: 1 elainedefreitascastroreis.pdf: 3548670 bytes, checksum: 46c9a924e7e08aa3c3e9f25546e3d941 (MD5) Previous issue date: 2008-09-22 / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Os fármacos imunossupressores se apresentam como as principais substâncias que afetam a resposta imune, diminuindo tanto a imunidade inata quanto a imunidade adquirida. As drogas imunossupressoras são geralmente utilizadas no tratamento de várias doenças auto-imunes, algumas alergias, e prevenção e/ ou tratamento da rejeição de transplantes. O objetivo do presente trabalho foi sintetizar, caracterizar e avaliar a atividade biológica de novos aminoálcoois lipofílicos. Para síntese destes compostos foi realizada a reação de um diol comercial (1,2-tetradecanodiol) com cloreto de mesila em piridina para formação do 1-o-monomesilato correspondente. Este, por sua vez, foi tratado com duas diaminas (1,2- etanodiamina e 1,3- propanodiamina), formando assim as diaminas monoalquiladas correspondentes. O referido monomesilato foi também tratado com quatro aminoálcoois para fornecer os correspondentes derivados N-alquilados. Após a purificação, foi feita a caracterização dos produtos por espectroscopia no infravermelho e ressonância magnética nuclear de 1H e de 13C. A avaliação “in vitro” da atividade biológica das substâncias obtidas foi realizada utilizando-se a linhagem de macrófagos J774, estimulada com BCG e IFN-g. Avaliou-se a produção de óxido nítrico (NO) através do Método de Griess, a viabilidade celular e a citotoxicidade pelo Método do MTT. Os compostos 10 na concentração 0,05 mg/ mL; os compostos 11, 12, 16, 19 nas concentrações 0,5 mg/ mL e 0,05 mg/ mL, e o composto 14 nas concentrações 0,5 mg/ mL e 0,005 mg/ mL se destacaram por diminuírem a produção de NO, sem interfirirem na proliferação celular e sem serem citotóxicos, com resultados sugestivos de atividade imunossupressora. A avaliação “in vivo” dos compostos 12 e 19, foi realizada utilizando o modelo de Reação de Hipersensibilidade Tardia (RHT) para a proteína ovalbumina. Ambos os compostos apresentaram atividade imunossupressora. / Immunosuppressant drugs are the main drugs that can affect the immune response, reducing the activation of the innate and acquired immunities. The immunosuppresive drugs are used in the treatment of several autoimmune diseases, some allergies, and in the prevention and/or treatment of the rejection of transplanted organs and tissues. The objective of the present work is the synthesis, characterization and evaluation of the biological activity of new lipophilic aminoalcohols. For synthesis of the desired compounds, a commercial diol (1,2-tetradecanediol) was treated with mesyl chloride leading to the corresponding monomesylate. The late compound was treated with a diamine (1,2-ethanediamine or 1,3-propanediamine), to furnish the corresponding Nmonoalkylated diamines. The monomesylate was also treated with four aminoalcohols, leading to the correspondings N–alkylated derivatives. After purification, the compounds were characterized by IR and 1H NMR and 13C NMR spectroscopy. The in vitro evaluation of the biological activity of the compounds was carried out using the lineage cell J774.1, stimulated with BCG and IFN-g. The Griess Method was used for determining the production of nitric oxide (NO), and the cytotoxicity of the compounds was evaluated by the MTT Method. Compound 10 at the concentration of 0.05 mg/ mL; compounds 11, 12, 16, 19 at the concentrations of 0.5 mg/ mL and 0.05 mg/ mL, and compound 14 at the concentrations of 0.5 mg/ mL and 0.005 mg/ mL decreased significantly the production of NO, but did not decrease the cell proliferation and were not cytotoxic. These results suggest an immunosuppressive activity. The in vivo evaluation of compounds 12 and 19 was realized using the delayed-type hypersensitivity (DTH) reaction against ovalbumin (OA), where both compounds showed immunosuppressive activity.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-05-09T20:30:54Z No. of bitstreams: 1 camilaguimaraesdealmeida.pdf: 3524589 bytes, checksum: 729e2c75b5b9d13a5afa527ed90143ff (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-17T14:36:03Z (GMT) No. of bitstreams: 1 camilaguimaraesdealmeida.pdf: 3524589 bytes, checksum: 729e2c75b5b9d13a5afa527ed90143ff (MD5) / Made available in DSpace on 2017-05-17T14:36:03Z (GMT). No. of bitstreams: 1 camilaguimaraesdealmeida.pdf: 3524589 bytes, checksum: 729e2c75b5b9d13a5afa527ed90143ff (MD5) Previous issue date: 2010-07-30 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Os aminoálcoois constituem uma importante classe de compostos orgânicos, devido a sua ocorrência comum na natureza, além de serem versáteis blocos construtores para a síntese orgânica. Isto pode ser confirmado pelo grande número de moléculas sintetizadas a cada ano contendo esse grupamento, dando destaque aos compostos com atividade imunossupressora ou antimicrobiana. Neste trabalho são descritas as sínteses de aminoálcoois e aminas derivados de heterociclos aromáticos tais como o furano e o tiofeno, usando o FTY720 como composto protótipo. Uma primeira série de compostos foi obtida por aminação redutiva do furfuraldeído, do 5-bromo-furfuraldeído e do tiofenocarboxialdeído com aminoálcoois ou octilamina. A segunda série de compostos foi obtida em duas etapas por reação dos alcoóis 2-furfurílico, 5-bromo-furfurílico e 2-tiofenílico com a epicloridrina, seguida pelo tratamento dos éteres glicídicos obtidos com aminoálcoois ou octilamina, fornecendo os aminoalcoóis correspondentes. Após purificação e caracterização dos compostos através dos métodos espectroscópicos usuais (RMN 1H e 13C, infravermelho) suas propriedades biológicas foram avaliadas in vitro. A atividade antiinflamatória foi estudada através da capacidade dos compostos em inibir a produção de óxido nítrico por macrófagos ativados. Foram também avaliados a citotoxicidade, pelo método do MTT, e o potencial antimicrobiano contra bactérias Gram-positivas, Gram-negativas e contra M. Tuberculosis. Os resultados mostraram que a atividade depende da lipofilicidade das moléculas, já que os compostos mais ativos possuem a cadeia octilamina. / Amino alcohols are an important class of organic compounds due to their common occurrence in nature, and they are versatile building blocks for organic synthesis. This can be confirmed by the large number of molecules synthesized each year containing this group, emphasizing compounds with immunosuppressive or antimicrobial activity. This work describes the synthesis of aminoalcohols and amines derivatives of aromatic heterocycles such as furan and thiophene, using FTY720 as a prototype compound. A first series of compounds was obtained by reductive amination of furfural, 5-bromo-furfural and thiophene-2-aldehyde with aminoalcohols or octylamine. The second series of compounds was obtained in two steps by reaction of 2-furfuryl, 5-bromo-furfuryl and 2-thiophen methyl alcohols with epichlorohydrin, followed by the treatment of the obtained glycidic ethers with amino alcohols or octylamine, furnishing the corresponding amino alcohols. After purification and characterization of the compounds through the usual spectroscopic methods (1H and 13C NMR, infrared), their biological properties were evaluated in vitro. The antiinflammatory activity was studied through the ability of the compounds to inhibit the production of nitric oxide by activated macrophages. We also evaluated the cytotoxicity by the MTT method and the antimicrobial potential against M. tuberculosis, Gram-positive and Gram-negative bacteria. The results showed that the activity depends on the lipophilicity of the molecules, since the most active compounds carry the octylamine chain.

Orientador: Ronaldo Aloise Pilli / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-04T07:43:02Z (GMT). No. of bitstreams: 1 Lapis_AlexandreAugustoMoreira_D.pdf: 8284160 bytes, checksum: ba07d6bcefdd0d627c338d01a09fa12e (MD5) Previous issue date: 2005 / Doutorado / Quimica Organica / Doutor em Quimica

Aminoalcohols are very important compounds used in various asymmetric transformations as chiral ligands or chiral auxiliaries. In this thesis, four novel heterocyclic amine substituted chiral 1,4-aminoalcohols were synthesized. In the synthetic strategy, amide esters were synthesized from (2S, 3R)-3-methoxycarbonylbicyclo[2.2.1]hept-5-ene-2-carboxylic acid by DCC coupling method. Subsequent reduction of these amide esters lead to target 1,4-aminoalcohols. The activities of these novel chiral 1,4-aminoalcohols were tested in enantioselective diethylzinc addition, Mukaiyama aldol and Diels-Alder reactions. The enantioselectivities were measured by HPLC. All the products were identified by H NMR and C NMR spectroscopy

(FOR FIGURES REFER THE MAIN PDF FILE) Supramoleculr chemistry, aptly termed by Lehn as the study of molecular sociology, is the chemistry of the intermolecular bond, focusing on the structures and functions of “supermolecules” –chemical system formed by the association between two or more molecular components. While interrelated, this discipline forges beyond the domain of traditional molecular chemistry, which seeks to master the manipulation of the covalent bond between atoms and uncover the principle that governs the structures and properties of molecular species. Supramolecular chemistry assayas to blend the comprehensive resources of molecular chemistry with designed control of the intermolecular interactions to engineers supramolecular with features as well defined as those of the constituent molecular themselves. Not surprisingly, it has been stated that supramoleculars are to molecules and the intermolecular bond what molecules are to atoms and the covalent bond. In the realm of molecular crystals, the focus of supramolecular chemistry and indeed, the scope of the present thesis coverings with that of a rather recent, but rapidly emerging scientific discipline, namely crystal engineering. Coined nearly four decades ago in connection with photodimerization reaction in crystalline cinnamic acids, the term” crystal engineering” has since then broadened its expanse considerably and is, at present, most appropriately defined as“the understanding of intermolecular interactions in the context of crystal packing and the utilization of such understanding in the design of new solids with desired physical and chemical properties”. It would be befitting to remark that it is very pursuit (and more often than not, the elusive target) of being able to make functional solids by design that has allowed crystal engineering to evolve from an object of mere Scientific curiosity to a subject of tremendous utilization value. No proof for this assertion might be greater than that which lies in the fervent efforts put forth by pharmaceutical companies in understanding and controlling drug polymorphism, especially in the wake of the contemporary legal implications attendant with observing such a phenomenon. Polymorphism in molecular crystals results from the possibility of at least two different arrangements of the molecular of a given compound in the solid state and has therefore often been regarded as the” dark side” of crystal engineering. On one hand, polymorphism presents itself as an important probe in the study of structure-property relationship and allows elucidation of the varied macroscopic properties of the same molecule self-assembled in different crystalline environments. On the other hand, the phenomenon poses an implicit complication when predicating the product of a crystallization process forms the goal of a crystal engineering project. This is particularly true in case of crystal structure prediction (CSP) from the molecular structure of a given compound, where the experimentally obtained polymorphic modification may be a kinetic form and therefore, need not correspond to the one ranked lowest in energy from the computational studies. Indeed, this dichotomy between a thermodynamically and a kinetically controlled crystallization process reflects the underlying uncertainty associated with judging the outcome of a crystallization event. In this concept of a supramolecular synthon has been postulated to assimilate both thermodynamic and kinetic alternative, and therefore provide a working model for heuristic crystal design. By analogy with corey’s definition of a molecular synthon, a supramolecular synhon has been described” a structural unit within a supramolecule which can be formed and/or assembled by known or conceivable synthetic operations involving intermolecular interactions”. Being entirely probabilistic in nature, the robutness and thus, the transferability of a particular synthon to a designed crystal is assessed from a systermatic evolution of its recurrence in crystal structures of representative molecules. The Cambridge Structural Database (CSD), which announced the inclusion of the 500000th crystal structures in its archives last year, provides an invaluable cache of experimentally determined structures and the foundation for crystal design in this regard. The practically of the supramolecular synthon approach, now almost synthymous with crystal engineering, has been demonstrated not only in the successful design of a number of functional solids, but also in its possible application in CSP as a knowledge-based alternative. Irrespective of the approach, a basic paradigm can however be constructed from any crystal engineering strategy, viz. construct the molecular building blocks and assemble these, with a prior knowledge of the possible non-covalent interactions, in a manner that leads to the desired crystal structure. This premise will form the central theme of the present thesis, entitled “From molecular to supramolecular: Probing solid state self –assemblies of conformatonally locked polycyclitos and structural siblings”. The dissertation will deal with the nuances of the self-assemblies of four classes of structurally related crystalline polycyclie compounds, all fashioned from a prototypical rigid trans-decalin backbone derived from commonly available aromatic precursors like naphthalene and anthracene. The thesis will be presented in four chapters, each based on one of the four functional make-ups present in the molecular under study. • Chapter 1.Relating intramolecular O-H…Ohydrogen bondigs to conformational locking: Design and self-assemblies of crystalline polyclitols. • Chapter 2.Preferences of supramolecular assemblies towards competing inter- and intramolecular O-H…O hydrogen bonds: A case study in crystalline acyldervaeives of conformarionally locked polyclitols. •Chapter 3.Synthesis of novel polyhydroxylated flustrates: Probing fluorine interactions in a conformatonally constructed environment. • Chapter 4. Strength vs.accessiblity: Universe the patterns of self-recognition in designer conformationally locked aminoacohols. A brief overview of each chapter is presented below. The first chapter of the thesis investigates the supramolecular chemistry of an O-H…O Hydrogen Bond formed between hydroxyl groups that have been constrained to occupy spatiality invariant position in the crystal structure of a polycyclitol (a portmanteau word derived from polycyclic cyclitol). Having been constructed on a grid trans-decalin carbocyclic backbone, the polycyclitols under study 1-6 are conformatonally locked and destined to exhibit an axial rich disposition of the hydroxyl groups, so that the OH functionalities in 1,3-relationship are automatically brought into a favorable geometry for the formation of intramolecular O-H…O hydrogen bonds. Working within this paradigm, which was formulated both logically and on the basis of the observed H-bonding patterns in the crystal structures of several conformationally locked polyols, we were able to demonstrate that intramolecular H-bonding between 1,3-syndisxial OH groups can be used as a tool to preordain the position of the intermolecular O-H…O-bond donors and accepts in the specially crafted polycyclitols 1-3. this observation not only simplified a qualitative visualization of the various packing patterns in 1-3, but also allowed us to propose, based on previously reported CSD analysis, the packing motifs mostlikely to converge with the experimental results. Despite its qualitative nature, the O-H…O hydrogen bonding patters, proposed for 1-3 were found to conform well with those observed experimentally for the tetrols 1 and 3, and even for the two polymorphic modifications of the hexol 2[Figure 1] The determination role played by intramolecular O-H…O bonding in the supramolecular assembly of 2, a novel bicycle C2h symmetric hexol having an all axial disposition of the six hydroxyl functionalities, prompted us to study the crystal packing of the three diastereomeric perhydro-2,3,4q,6,6,8a-naphthalenehexols 4-6. the end-to-end co-operative intramolecular O-H…O-H hydrogen bonding chain on both faces of the molecule, as observed in case of 2, through an axial-equatorial. Figure 1. (left) one of the packing modes proposed for the hexol 2. Note that the H-bonding pattern involves all donor/acceptor oxygen and incorporates infinite chains of O-H…O bonds of O-H….O bonds; (right) Molecular packing observed experimentally in the polymorph of the hexol 2 Transposition of one or more of the peripheral yhdroyl groups. With increased freedom now allowed to the OH groups in the choice of their H-bonding partners, as a compared to 2 crystal packing in the polycyclitols 4-6 evolved from the simplistic model of hydrogen bonding proposed and observed for 2,to ivoke more complex patterns of self assembly mediated through O-H…O-bonds In the second chapter, the crystal structures of four conformationally locked esters, namely tetraaccetate 7/tetrabenzoate 8 of hexol 2 and the diacetate9/dibenzoate 10 of tetrol1,have been analyzed in order to examine the preference of their supramolecular assemblies towards competing inter and intramolecular O-H…O hydrogen bonds. To this end, all the four esters under study were specially crafted on a trans-decalin backbone with the objective of relegating the O-H…O H-bond donors( in form of the 30 OH groups) to the molecular interior and having the peripheral H-bond accepters (in form of the 20 acyl groups) in 1,3-syndiaxial relationship. It was anticipated that this common design element would allow the supramolecular assembly of the easters to evolve along two possible pathway, namely one which employs intermoleculars O-H…O H-bonds (pathway 1) and the other that sacrifises those for intramolecular O-H…O H-bonds and settles for a crystal packing dictated by weak intermolecular interactions alone (pathway 2) A pure sample of 7 crystallized along pathway 1 in two enantiotropic modifications, one obtained at room temperature (form) and the other at 20 C0 (form) [Figure 2]. Behaving much like a temperature guided molecular switch, the tetraacetate 7 could be shifted reversibly between the forms response to changes in the ambient temperature. Thus, the form converted at -4 OC to the denser form, which displayed an unusual kinetic stability till 67 OC and transformed back to the form beyond this temperature. Subsequently, the close similarity between the self-assemble of the two dimonrphs of 7 and the diastereomer 11 was exploited in order to stimulated 7 to fallow the pathway 2 through preferential inhibition of pathway 1[Figure 3]. Interstingly, the nucleation inhibition 11 was obtained serendipitously a route 7 via an apparent breakdownof furst-platter rule. Unlike the tetraceatate 7, crystal packing in the tetrabenzoate 8 preferred to fallow exclusively pathway 2. The individualistic nature of the self-assemblies of 7 and 8 found to be in contrast commonalities noted in the mode of molecular assembly in 9 and 10 both of which conformed to a combination of pathway 1 and 2. A rationale for the preferred crystallization pathway of the four estes 7-10 as well as probable mechanism for the observed reversible transformation between the forms the tetracetate 7 will be put forth in this chapter. Figure 2. (Model for pathway 1) Molecular packing in the forms of the tetraacetate 7. The non-interacting hydrogen atoms have been omitted for clarity. Figure 3. (Model for pathway 2) The nucleation inhibitor 11 and form of the tetraacetate 7. The non-interacting hydrogen atoms have been omitted in the molecular packing diagram for clarity. In light of the wide ranging application of organofluorine compounds and the ambiguity that resides over the disposition of fluorine as a H-bond accepter, the third chapter utilizes three specially designed fluorinated polycyclitols 12-14 investigate the role of covalently bonded flurine in crystal structures of lesser studied aliphatic fluorous substracts and probe its capacity to engage itself in C(sp3)-F…H-X(sp3)(X=O and/or C) H-bounding, in presence of its isostere, the hydrozyl group. Conformatonality locked with well defined spatial disposition of functional groups, all the fluorinated polycyclitols 12-14 bear a fluorohydrin moiety, embedded in a rigid trans-decalin framework. In 12 and 14, it was conceived that the presence of a hydroxyl donor in a favorable 1, 3-syndiaxial relationship to a fluoro group on one side and a hydroxyl group on the other would allow an unambiguous comparison between the two isoteric functionalities (C-OH and C-F) to serve as acceptors for intramolecular hydrogen bonds (O-H…O and purported O-H…F respectively) The difluorodiol 13 was sought to serve as a control to assess the change in the C-F…H-X interactions (if any) which might be observed upon incorporating the peripheral secondary hydroxyl groups in 14. The result presented in this chapter will revel, in particular, that C(sp3) –F…H-C(sp3) hydrogen bonds, though weak and lesser investigated, can indeed be observed and supramolecular recognition motifs, involving such interactions, can be conserved even in crystal structures laden with stronger O-H…O hydrogen bonds [Figure 4}. Figure 4. (Left) Molecular packing in the difluorodiol 13, showing how four intermolecular C-H…F hydrogen bonds forms a part of a R22 H-bonding motif (encircled). This centrosymmentic supramolecular recognition unit is observed even in the molecular packing in the difluorohexol 14 (right). Non-interacting H atoms have been omitted in both diagrams for the sake of clarity. The forth chapter details an in-depth study carried out on the self-assembly of a conformationally locked aminoalchohol 15, in which the amino protons serve as mere spectators, the molecular packing in the crystal being realized through the co-operativity between O-H…N H-bonds and weak π-π stacking interaction (Figure 5b). The crystal structure of 15 was quite intriguing on three sailent grounds (a) previous studies on the supramolecular assemblies in the aminols have shown that both amino and hydroxyl protons participate in H-bonding in the crystal structures of such compounds; (b) the fact that the hydrogen atoms of the NH2 group Figure 5. (Left) Laplacian distribution map in the planes defined by (a) the double bonds, (c) O-H…N-H-bond, and (d) π-π stacking interactions in the aminoalclhol 15. Contours havse been drawn at logarithmic intervals in ▼2 ρb, eÅ-5. Solid lines indicate positive contours and dotted lines negative contours. (b) Molecular packing in 15. Non-interacting H atoms have been omitted for the sake of clarity.remain as mere bystanders in anomalous if one were to abide by the Etter’s rule; (c) the rather well-difined π-π stacking interactions in crystal structure of the aminoalcohol occurs between isolated olefinic bonds-a rarely encountered form of non-covalent interaction. Charge destiny analysis was carried out on the aminoalcoholf 15 not only to catheterize the non-covalent interactions existing in the supramolecular assembly in terms of topological features of electrol destiny at their bond critical points, but also to confirm the non-involvement of the amino H-atoms in any form of either intra- or intermoalecular hydrogen bonds beyond the criteria of mere geometry (Figure a,c,d). The maverick nature of the self-assembly of 15 was elucidated as resulting from the preference of the molecules to assemble with O-H…N H-bonds. This automatically relegated the hydrogen atoms of the tertiary amine to the interior of the conformationally locked cabocycclic scaffold, thereby making them far less accessible than the peripheral C=C bonds.