Academic literature on the topic 'Diazocan'

The sulfonamide moiety was evaluated as an activating and stabilizing functional group in the metal templated strain release-driven intramolecular nucleophilic addition of amines to cyclopropenes to generate 1,5-diazocan-2-ones.

A modular synthetic approach is described in which combinations of cyclic sulfamidate and hydroxy sulfonamide building blocks may be converted into piperazine, 1,4-diazepine and 1,5-diazocane scaffolds.

Correction for ‘Tandem Prins cyclization for the synthesis of indole fused spiro-1,4-diazocane scaffolds’ by Chandrashekhar Rapelli et al., Org. Biomol. Chem., 2020, 18, 6710–6715, DOI: 10.1039/D0OB01384F.

A novel approach for the synthesis of unsymmetrically substituted dibenzo[b,f][1,5]diazocine-6,12(5H,11H)diones has been developed. This facile three-step method uses variously substituted 1H-benzo[d][1,3]oxazine-2,4-diones (isatoic anhydrides) and 2-aminobenzoic acids as a starting materials. The obtained products were further transformed into N-alkyl-, N-acetyl- and dithio analogues. Developed procedures allowed the synthesis of unsymmetrical dibenzo[b,f][1,5]diazocine-6,12(5H,11H)diones and three novel heterocyclic scaffolds: benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)dione, pyrido[3,2-c][1,5]benzodiazocine-5,11(6H,12H)-dione and pyrazino[3,2-c][1,5]benzodiazocine-6,12(5H,11H)dione. For 11 of the compounds crystal structures were obtained. The preliminary cytotoxic effect against two cancer (HeLa, U87) and two normal lines (HEK293, EUFA30) as well as antibacterial activity were determined. The obtained dibenzo[b,f][1,5]diazocine(5H,11H)6,12-dione framework could serve as a privileged structure for the drug design and development.

A solvent-dependent chemodivergent approach was developed for the synthesis of 6,12-methanodibenzo[b,f][1,5]diazocin-13-ylmethanones and 2,3,4-trisubstituted 1,2,3,4-tetrahydroquinolines involving two distinct AB₂ and A₂B₂ multicomponent processes.

A tandem Prins strategy has been developed for the first time to produce a novel class of spiro-1,4-diazocane derivatives by the condensation of indole tethered γ-hydroxyolefin with aldehydes using BF₃·OEt₂ at −40 °C in dichloromethane.

Unsymmetrically N-substituted and N,N’-disubstituted 5,12-dihydrodibenzo [b,f][1,4]diazocine-6,11-diones were synthesized in the new protocol. The desired modifications of the dibenzodiazocine scaffold were introduced at the stages of proper selection of building blocks as well as post-cyclization modifications with alkylation or acylation agents, expanding the structural diversity and possible applications of synthesized molecules. The extension of developed method resulted in the synthesis of novel: tricyclic 5,10-dihydrobenzo[b]thieno[3,4-f][1,4]diazocine-4,11-dione scaffold and fused pentacyclic framework possessing two benzodiazocine rings within its structure. Additionally, the unprecedented rearrangement of 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-diones to 2-(2-aminophenyl)isoindoline-1,3-diones was observed under the basic conditions in the presence of sodium hydride for secondary dilactams. The structures of nine synthesized products have been established by single-crystal X-ray diffraction analysis. Detailed crystallographic analysis of the investigated tri- and pentacyclic systems has shed more light on their structural features. One cell line derived from non-cancerous cells (EUFA30—human fibroblasts) and three tumor cells (U87—human primary glioblastoma, HeLa—cervix adenocarcinoma, BICR18—laryngeal squamous cell carcinoma) were used to determine the cytotoxic effect of the newly synthesized compounds. Although these compounds showed a relatively weak cytotoxic effect, the framework obtained for 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-dione could serve as a convenient privilege structure for the design and development of novel bioactive molecules suitable for drug design, development and optimization programs.

Pyrroles are found in various natural products and in the chemical composition of certain drugs because of their interesting biological properties. Lipitor, Tolmetin and Amtolmetin are examples of drugs with 1,2,5-substituted pyrroles in their composition, in which biological activities have been certified. Moreover, pyrroles are used as precursors of semiconductor polymers, oligomers and dendrimers useful for the synthesis of electroluminescent materials used in devices, such as organic light-emitting diodes, field-effect transistors, solar and organic photovoltaic cells. We are interested in conjugated polymers based on pyrrole due to their optical properties, electrochemical and the conductivity produced by electron delocalization along their carbon chains. The overall objective of the work presented in this thesis is the synthesis of new molecules based on pyrrole for studying their electronic and electrochemical properties as well for the synthesis of conjugated polymers. Initially, we performed the synthesis of 1,3,5-tri-(1-alkyl-5-methylpyrrol-2-yl)benzenes, which may serve as precursors for the synthesis of conjugated dendrimers. Their synthesis was made in three steps starting from trimethyl 1,3,5-benzene-tricarboxylate which was converted to 1,3,5-tri-(pent-4-enoyl)benzene using vinylmagnesium bromide in a Grignard reaction catalyzed by copper cyanide. The olefins of 1,3,5-tri-(pent-4-enoyl)benzene were oxidized to produce 1,3,5-tri-(4-oxopentanoyl)benzene using a modified protocol of the Tsuji-Wacker reaction. Subsequent, Paal-Knorr condensation reactions on 1,3,5-tri-(4-oxopentanoyl)benzene with different amines were used to synthesize 1,3,5-tri-(1-alkyl-5-methylpyrrol-2-yl)benzenes with different N-substituents in yields between 44 and 60%. Incomplete reaction of vinylmagnesium bromide with trimethyl 1,3,5-benzenetricarboxylate gave the methyl-3,5-di(pent-4-enoyl)benzoate, which was converted to methyl-3,5-dipyrrolylbenzoate following the reaction of Tsuji- Wacker and Paal-Knorr with yields between 30 and 60%. The photochemical and electrochemical properties of the 1,3,5-tri-(1-alkyl-5-methylpyrrol-2-yl)benzenes and methyl-3,5-dipyrrolylbenzoates were studied in collaboration with the research group of professor William Skene. The results have shown that both types of pyrrole have potential for the synthesis of conjugated polymers and dendrimers used in the manufacture of electroluminescent materials. Following these encouraging results, we performed the synthesis of 6,12-dimethyl-1,5-dipyrrolediazocane. Methyl N-(Boc)-β-alaninate was converted to its corresponding homoallylic ketone, which was oxidized to N-(Boc)aminoheptan-3,6-dione. The Paal-Knorr condensation between N-(Boc)aminoheptan-3,6-dione and aminoheptan-3,6-dione hydrochloride gave 6,12-dimethyl-1,5-dipyrrolediazocane in 17% yield. In sum, we have synthesized and characterized seven new molecules, six of them having photochemical and electrochemical properties interesting for the synthesis of conjugated polymers and dendrimers. The latter offering potential as precursor for the conception of compounds of therapeutic interest.
Les pyrroles sont une classe de molécules que l'on trouve dans divers produits naturels ainsi que dans la composition chimique de certains médicaments en raison de leurs propriétés biologiques intéressantes. Le Lipitor, la Tolmetin et l'Amtolmetin sont des exemples de médicaments à base de pyrroles 1,2,5 substitués dont les activités biologiques ont été certifiées. Les pyrroles sont aussi utilisés comme précurseurs de polymères, oligomères et dendrimères semi-conducteurs nécessaires à la synthèse de certains matériaux électroluminescents, tels que les diodes organiques électroluminescentes, les transistors à effets de champ et les cellules organiques photovoltaïques. Nous nous sommes intéressés à ces polymères conjugués à base de pyrroles en raison de leurs qualités de bons conducteurs, de leurs propriétés optiques et électrochimiques que leur confère la délocalisation des électrons le long de leurs chaines carbonées. L'objectif général des travaux présentés dans ce mémoire est de synthétiser de nouvelles molécules à base de pyrroles pouvant éventuellement servir de précurseurs à la synthèse de dendrimères conjugués ainsi qu'à la synthèse de molécules thérapeutiques. Une étude de leurs propriétés électroniques et électrochimiques sera effectuée afin de déterminer leur potentiel pour la fabrication de matériaux électroluminescents. Dans un premier temps, la synthèse des analogues du 1,3,5-benzènetripyrrole a été faite en trois étapes à partir du 1,3,5-benzènetricarboxylate de triméthyle. Celui-ci a été converti en premier lieu en 1,3,5-benzènetricétone-γ,δ-insaturée lors d'une réaction de Grignard catalysée par le cyanure de cuivre. Ce dernier composé fut oxydé lors de la seconde étape en 1,3,5-tri-(4-oxopentanoyl)benzène selon un protocole modifié de la réaction de Tsuji-Wacker. Enfin, la réaction de condensation de Paal-Knorr du 1,3,5-tri-(4-oxopentanoyl)benzène de l'étape précédente mène au 1,3,5-benzènetripyrrole N-substitué selon l'amine utilisée pour la condensation, avec des rendements entre 44 et 60%. La réaction incomplète du bromure de vinylmagnésium avec le 1,3,5-benzènetricarboxylate de triméthyle mène au méthyl-3,5-di-(pent-4-énoyl)benzoate, qui a été converti en méthyl-3,5-dipyrrolylbenzoate suite à la réaction de Tsuji-Wacker et de Paal-Knorr avec des rendements entre 30 et 60%. L'étude des propriétés photochimiques et électrochimiques des tripyrroles et des bipyrroles a été faite en collaboration avec le groupe de recherche du professeur William Skene. Les résultats obtenus démontrèrent que ces pyrroles auraient un potentiel pour la synthèse de dendrimères conjugués servant à la fabrication de matériaux électroluminescents. Suite à ces résultats encourageants, la synthèse du 6,12-diméthyle-1,5-dipyrrolediazocane a aussi été réalisée. Celui-ci a été synthétisé à partir de l’ester méthylique de l’acide 3-tert-butoxycarbonylaminopropionique qui a été converti en sa cétone homoallylique correspondante, puis oxydée en N-Boc-3,6-dioxoheptylcarbamate. La condensation de Paal-Knorr de ce dernier composé avec le sel d'hydrochlorure 7-aminoheptane-2,5-dione mène au 6,12-diméthyle-1,5-dipyrrolediazocane avec un rendement de 17%. En somme, la recherche effectuée a permis la synthèse et la caractérisation de six nouvelles molécules ayant des propriétés photochimiques et électrochimiques intéressantes pour la synthèse de polymères et dendrimères conjugués. Ainsi que la synthèse d'un diazacycle, qui de part sa structure pourrait servir de précurseur à la synthèse de molécules thérapeutiques.

博士
國立交通大學
應用化學系碩博士班
106
This dissertation describes the development of new synthetic organic transformations by using metal free catalyst and with metal catalyst. Transition metal free catalyst transformations such as Pictet-Spengler reaction and with transition metal-catalyst transformation such as [5+2] annulation are described in this dissertation. For sake of convenience and better understanding, the thesis is divided into four chapters. The first chapter deals with the synthesis of structurally diverse indole-fused diazocine and diazepine derivatives. A substrate-based diversification approach of methyl-3- aminoindole/ indoline benzoates coupled with the Pictet−Spengler reaction and three different reaction cascades furnished indolodiazepine and indoloquinoxalines. The formation of indolodiazocines proceeds through an initial condensation followed by intramolecular alkylation. In the second chapter describes an efficient and regioselective Pd(II)-catalyzed [5+2] annulation of unprotected o-indolo anilines with internal alkynes under microwave irradiation. The diverse imine-containing 1,2-fused indole [1,7-a] diazepines are constructed in moderate to excellent yields. The mechanistic pathway shows pivalic acid and molecular oxygen to play crucial roles for the regeneration of highly active electrophilic Pd-species in the catalytic cycle. The third chapter emphasized the efficient and regioselective synthesis of novel 1,2,3- triazole-fused-1,5-benzoxazocinones through intramolecular cyclization of substituted ethynyl triazoyl benzoic acids. A crucial precursor 5-iodo-1,2,3-triazole benzoate was obtained from substituted 2-azido benzoic acid esters in a single step through a Copper- Catalyzed Azide−Alkyne Cycloaddition (CuAAC) reaction using a CuI/NBS catalytic system. A carbon−carbon triple bond was installed through a Sonogashira coupling reaction by various terminal alkynes. Finally, the 1,4,5-substituted ethynyl triazoyl benzoic acids were cyclized by a AgOTf mediated intramolecular cyclization to afford 8-endo-dig 1,2,3-triazolefused- 1,5-benzoxazocinones exclusively. The fourth chapter deals with a facile and efficient synthesis of novel oxo, thio and selenohydantoin fused tetrahydroazepino [4, 5-b]indoles. Naturally occurring iboga class alkaloid inspired seven-member azepino[4,5-b]indole ring was synthesized as a new scaffold through Pictet-Spengler reaction followed by skeletal rearrangement of aziridine ring. To improve the efficiency of the synthetic route, the double bond of the rearranged olefinic product was reduced and privileged hydantoin moiety was constructed on the core system through urea formation using variety of isocyanates, isothiocyanates and isoselenocyanates followed by intramolecular cyclization to incorporate elements of diversity. The regeneration of the double bond afforded hydantoin-fused tetrahydroazepino [4, 5-b]indoles.