Natural products as sources of novel therapeutic agents experienced a steady increase from around the turn of the twentieth century until it peaked in the 1970s and 1980s. However since this time pharmaceutical research in natural products has experienced a decline. Despite this trend the natural products industry now seems to be experiencing a revival of sorts. This thesis represents a continuation of the work on the isolation and structure elucidation of potential drug leads from terrestrial fungal sources that the natural products group at the University of Canterbury is engaged in. The known compound, pseurotin A (2.7) and two novel diastereomers, pseurotin A2 (2.8) and pseurotin A3 (2.9) were isolated from the extract of a Penicillium sp. of fungus collected from the foreshore of a beach in Vancouver, Canada. The absolute stereochemistry of pseurotin A2 and proposed absolute stereochemistry for A3 were elucidated using a combination of X-ray crystallography (A2 only), circular dichrosim, oxidative cleavage reactions, and J2-resoved 2D NMR experiments. The extract of an as yet unidentified endophytic fungus has yielded eight novel compounds related to the spirobisnaphthalene class of compounds. These eight compounds fall into to distinct groupings. The spiro-mamakones, distinguished by a structurally unprecedented oxygenated spiro-nonene skeleton, comprise five compounds, spiro-mamakones A-E (3.11, 3.15-3.18). In addition to these naturally occurring compounds, the semi-synthetic compounds, 4-oxo-spiro-mamakone A (3.12) and O-acetyl-spiro-mamakone A (3.21), were also synthesised. spiro-Mamakone A was found to be racemic, while X-ray crystallography and optical rotation revealed spiro-mamakone C (3.15) to be present as an enantiomeric mixture (4S*, 5S*, 9R*). Unfortunately the enantiomeric excess was unable to be elucidated. NOE experiments revealed spiro-mamakone B (3.16) to have the relative stereochemistry 4S*, 5S*, 9S*. The relative stereochemistry of spiro-mamakones D (3.17) (4S*, 5S*, 8S*, 9S*) and E (3.18) (4S*, 5S*, 8S*, 9R*) was proposed from comparison of coupling constant calculations from energy-minimised models with those of the experimentally determined values. The second group, comprising three novel compounds named the mamakunoic acids, mamakunoic acid A-C (3.8, 3.7, 3.10), are characterised by their acid substituted dihydro benzofuran system. The low yield obtained of these compounds, unfortunately prevented their stereochemical elucidation. In addition to structure elucidation, biosynthetic studies on spiro-mamakone A and mamakunoic acid B were also carried out. Analysis of the NMR spectra derived from spiro-mamakone A, labelled with isotopic acetate, revealed a situation complicated by the presence of isotopomers and racemisation, resulting in NMR spectra that were somewhat anomalous in appearance. These irregularities however, were resolved leading to the proposal that spiro-mamakone A was derived from a dihydroxynaphthalene (DHN) intermediate, which proceeds through to spiro-mamakone via an epoxide intermediate. Despite problems with purity and low yields of isotopically labelled mamakunoic acid B, it was proposed that like spiro-mamakone A, it proceeded via a DHN intermediate. The extract derived from a Malaysian Scleroderma sp. was found to contain a new dichlorinated pulvinic acid derivative, methyl-3',5'-dichloro-4,4'-di-O-methylatromentate (4.14), the structure of which was confirmed by X-ray crystallography. In addition three previously reported compounds, 4,4'-dimethoxyvulpinic acid (4.11), methyl-3'-chloro-4,4'-di-O-methylatromentate (4.12) and methyl-4,4'-dimethoxyvulpinate (4.13), were also isolated. The extract of another, as yet unidentified endophytic fungus was found to contain the new acetogenin, 1,5-dihydroxy-6-(2-hydroxyethyl)-3-methoxyacetophenone (5.7), differing from the known compound, 2,4-dihydroxy-6-(2-hydroxyethyl)-3-methoxyacetophenone (5.8) only by virtue of the substitution pattern. The structure of 5.7 was confirmed by X-ray crystallography. The implementation of efficient dereplication procedures is paramount for those working in the field of natural products. The recent advances that have been made in the dereplication process in the natural products group at the University of Canterbury are given using examples from this research and where necessary from other group members.

Natural products as sources of novel therapeutic agents experienced a steady increase from around the turn of the twentieth century until it peaked in the 1970s and 1980s. However since this time pharmaceutical research in natural products has experienced a decline. Despite this trend the natural products industry now seems to be experiencing a revival of sorts. This thesis represents a continuation of the work on the isolation and structure elucidation of potential drug leads from terrestrial fungal sources that the natural products group at the University of Canterbury is engaged in. The known compound, pseurotin A (2.7) and two novel diastereomers, pseurotin A2 (2.8) and pseurotin A3 (2.9) were isolated from the extract of a Penicillium sp. of fungus collected from the foreshore of a beach in Vancouver, Canada. The absolute stereochemistry of pseurotin A2 and proposed absolute stereochemistry for A3 were elucidated using a combination of X-ray crystallography (A2 only), circular dichrosim, oxidative cleavage reactions, and J2-resoved 2D NMR experiments. The extract of an as yet unidentified endophytic fungus has yielded eight novel compounds related to the spirobisnaphthalene class of compounds. These eight compounds fall into to distinct groupings. The spiro-mamakones, distinguished by a structurally unprecedented oxygenated spiro-nonene skeleton, comprise five compounds, spiro-mamakones A-E (3.11, 3.15-3.18). In addition to these naturally occurring compounds, the semi-synthetic compounds, 4-oxo-spiro-mamakone A (3.12) and O-acetyl-spiro-mamakone A (3.21), were also synthesised. spiro-Mamakone A was found to be racemic, while X-ray crystallography and optical rotation revealed spiro-mamakone C (3.15) to be present as an enantiomeric mixture (4S*, 5S*, 9R*). Unfortunately the enantiomeric excess was unable to be elucidated. NOE experiments revealed spiro-mamakone B (3.16) to have the relative stereochemistry 4S*, 5S*, 9S*. The relative stereochemistry of spiro-mamakones D (3.17) (4S*, 5S*, 8S*, 9S*) and E (3.18) (4S*, 5S*, 8S*, 9R*) was proposed from comparison of coupling constant calculations from energy-minimised models with those of the experimentally determined values. The second group, comprising three novel compounds named the mamakunoic acids, mamakunoic acid A-C (3.8, 3.7, 3.10), are characterised by their acid substituted dihydro benzofuran system. The low yield obtained of these compounds, unfortunately prevented their stereochemical elucidation. In addition to structure elucidation, biosynthetic studies on spiro-mamakone A and mamakunoic acid B were also carried out. Analysis of the NMR spectra derived from spiro-mamakone A, labelled with isotopic acetate, revealed a situation complicated by the presence of isotopomers and racemisation, resulting in NMR spectra that were somewhat anomalous in appearance. These irregularities however, were resolved leading to the proposal that spiro-mamakone A was derived from a dihydroxynaphthalene (DHN) intermediate, which proceeds through to spiro-mamakone via an epoxide intermediate. Despite problems with purity and low yields of isotopically labelled mamakunoic acid B, it was proposed that like spiro-mamakone A, it proceeded via a DHN intermediate. The extract derived from a Malaysian Scleroderma sp. was found to contain a new dichlorinated pulvinic acid derivative, methyl-3',5'-dichloro-4,4'-di-O-methylatromentate (4.14), the structure of which was confirmed by X-ray crystallography. In addition three previously reported compounds, 4,4'-dimethoxyvulpinic acid (4.11), methyl-3'-chloro-4,4'-di-O-methylatromentate (4.12) and methyl-4,4'-dimethoxyvulpinate (4.13), were also isolated. The extract of another, as yet unidentified endophytic fungus was found to contain the new acetogenin, 1,5-dihydroxy-6-(2-hydroxyethyl)-3-methoxyacetophenone (5.7), differing from the known compound, 2,4-dihydroxy-6-(2-hydroxyethyl)-3-methoxyacetophenone (5.8) only by virtue of the substitution pattern. The structure of 5.7 was confirmed by X-ray crystallography. The implementation of efficient dereplication procedures is paramount for those working in the field of natural products. The recent advances that have been made in the dereplication process in the natural products group at the University of Canterbury are given using examples from this research and where necessary from other group members.

Οι κυκλινοεξαρτώμενες κινάσες (Cdks) είναι μια κατηγορία των πρωτεϊνικών κινασών, οι οποίες ενεργοποιούνται μέσω σύνδεσης με την κατάλληλη κυκλίνη και εμπλέκονται στη ρύθμιση του κυτταρικού κύκλου. Η ενεργοποίηση συγκεκριμένων συμπλόκων Cdks-κυκλινών επιτρέπει την ομαλή μετάβαση από την μία στην επόμενη φάση του κύκλου. Ωστόσο, η υπερλειτουργία των Cdks οδηγεί σε ανεξέλεγκτο κυτταρικό πολλαπλασιασμό, με αποτέλεσμα την εμφάνιση διαφόρων ασθενειών, όπως είναι ο καρκίνος, η νόσος του Alzheimer και ο διαβήτης. Λόγω αυτού, οι Cdks αποτελούν υποψήφιους μοριακούς στόχους για την θεραπευτική αντιμετώπιση αυτών των ασθενειών. Πολλά μικρά χημικά μόρια έχουν αποδειχθεί αναστολείς των CDKs. Κάποιοι από αυτούς έχουν προχωρήσει σε κλινικές δοκιμές φάσης Ι και ΙΙ, ωστόσο κανένας δεν έχει λάβει έγκριση για κυκλοφορία. Πρόσφατα, ο Cdk αναστολέας Dinaciclib εισήλθε σε κλινικές δοκιμές φάσης ΙΙΙ. Τα θαλάσσια σφουγγάρια αποτελούν πλούσια πηγή φυσικών προϊόντων με ανασταλτική δράση έναντι πλήθους κινασών. Η Hymenialdisine (HMD) είναι ένα φυσικό προϊόν, το οποίο έχει απομονωθεί από διάφορα είδη θαλάσσιων σφουγγαριών και εμφανίζει ανασταλτική δράση έναντι πολλών πρωτεϊνικών κινασών, μεταξύ των οποίων και οι CDKs. Στα πλαίσια της παρούσας μελέτης σχεδιάσθηκαν και συντέθηκαν νέα σπειρανικά ανάλογα της HMD με σκοπό να εμφανίσουν ισχυρότερη και εκλεκτικότερη ανασταλτική δράση από αυτήν έναντι πρωτεϊνικών κινασών. Οι νέες ενώσεις φέρουν δομικά χαρακτηριστικά της HMD, όπως έναν πυρρολο[2,3-c]αζεπινονικό δακτύλιο που έχει αποδειχθεί κρίσιμος για την ανάπτυξη δεσμών υδρογόνου με τη θέση πρόσδεσης του ATP. Ωστόσο, ο γλυκοκυαμιδινικός δακτύλιος της HMD έχει αντικατασταθεί στα νέα ανάλογα από έναν εξαμελή λακταμικό σπειρανικό δακτύλιο. Η συνθετική προσέγγιση που ακολουθήθηκε για την σύνθεση των νέων ενώσεων περιελάμβανε αρχικά την ανοικοδόμηση του πυρρολο[2,3-c]αζεπινο-4,8-διονικού δακτυλίου και στην συνέχεια την μετατροπή της 4-κετο-ομάδας αυτού σε ένα αμινο-υποκατεστημένο στερεογονικό κέντρο. Για τον σκοπό αυτό, χρησιμοποιήθηκε μια κλασσική μεθοδολογία, η οποία περιελάμβανε συμπύκνωση του παραπάνω δακτυλίου με χειρόμορφα t-βουτυλοσουλφινυλαμίδια και νουκλεόφιλη προσβολή των ενδιάμεσων σουλφινυλιμινών που προέκυψαν με οργανομεταλλικά αντιδραστήρια Grignard. Η συνθετική προσέγγιση που ακολουθήθηκε επέτρεψε την σύνθεση εναντιομερών σπειρανικών αναλόγων της HMD. Η αποτίμηση της βιολογικής δράσης των νέων ενώσεων αναμένεται σύντομα. / Cyclin-dependent kinases (Cdks) are protein kinases and their enzymatic activity requires the binding of a regulatory cyclin subunit. Cdks are implicated in the regulation of the cell cycle. The activation of different Cdks-cyclin complexes drives the transition of cell through the distinct phases of the cell cycle. However, overactivation of Cdks results in uncontrolled cell proliferation and hence, in many diseases such as cancer, Alzheimer’s disease and diabetes. Cdks represent candidate molecular targets for the treatment of these diseases. Many small molecules have been proved potent Cdks inhibitors. Many of them, are in phase I or II of clinical trials. Recently, Dinaciclib became the first Cdk inhibitor which entered in phase III of clinical trials. The sea sponges are a rich source of natural products which present inhibitory activities against protein kinases. Hymenialdisine (HMD) is a natural product, which has been isolated from many sea sponges and inhibits many kinases, such as Cdks. In this research work, new spiro analogues of HMD were designed and synthesized, aimining at the discovery of new compounds with enhanced inhibitory activity and selectivity against to protein kinases. These new compounds bear structural characteristics of HMD, like a pyrrolo[2,3-c]azepinone ring, which is crucial for the binding of HMD to the ATP-binding site of the enzyme. The glycocyamidine ring of the HMD has been replaced by a six-membered lactam spiro-ring. The synthetis of new compounds involves the formation of the pyrrolo[2,3-c]azepino-4,8-dione and subsequently the introduction of a new amino-substituted stereogenic center. Key-step to this approach is the substitution of the intermediate chiral t-butanesulfinylimines by organometallic reagents. The synthetic approach provides access to different stereoisomers. The biological evaluation of the new compound is in progress.

In this thesis, I was paid to the preparation of enantiomerically and diastereomerically pure spiro compounds using asymmetric organocatalysis.

The rapid development in perovskite solar cells (PSC) has generated a tremendous interest in the photovoltaic community. The power conversion efficiency (PCE) of these devices has increased from 3.8% in 2009 to a recent certified efficiency of over 20% which is mainly the product of the remarkable properties of the perovskite absorber material. One of the most important advances occurred with the replacement of the liquid electrolyte with a solid state hole conductor which enhanced PCE values and improved the device stability. Spiro-OMeTAD (2,2',7,7'-tetrakis(N,N'-di-p-methoxyphenylamine)- 9,9'-spirobifluorene) is the most common hole transport material in perovskite solar cells. Nevertheless, the poor conductivity, low charge transport and expensive synthetic procedure and purification have limited its commercialisation. Triphenylamines (TPA) like Spiro-OMeTAD are commonly employed due to the easy oxidation of the nitrogen centre and good charge transport. Other triarylamines have similar properties to Spiro-OMeTAD but are easier to synthesise. The aim of this doctoral thesis is to investigate different types of hole transport materials in perovskite solar cells. Three different series of triphenylamine-based HTM were designed, synthesised, characterised and studied their function in perovskite solar cells. A series of five diacetylide-triphenylamine (DATPA) derivatives (Chapter 3) with different alkyl chain length in the para position was successfully synthesised through a five step synthesis procedure. A range of characterisation techniques was carried out on the molecules including; optical, electrochemical, thermal and computational methods. The results show that the new HTMs have desirable optical and electrochemical properties, with absorption in the UV, a reversible redox property and a suitable highest occupied molecular orbital (HOMO) energy level for hole transport. Perovskite solar cell device performances were studied and discussed in detail. This project studied the effect of varying the alkyl chain length on structurally similar triarylamine-based hole transport materials on their thermal, optical, electrochemical and charge transport properties as well as their molecular packing and solar cell parameters, thus providing insightful information on the design of hole transport materials in the future. The methoxy derivative showed the best semiconductive properties with the highest charge mobility, better interfacial charge transfer properties and highest PCE value (5.63%). The use of p-type semiconducting polymers are advantageous over small molecules because of their simple deposition, low cost and reproducibility. Styrenic triarylamines (Chapter 4) were prepared by the Hartwig-Buchwald coupling followed by their radical polymerization. All monomers and polymers were fully characterised through electrochemical, spectroscopic and computational techniques showing suitable HOMO energy levels and desirable optoelectrochemical properties. The properties and performance of these monomers and polymers as HTMs in perovskite solar cells were compared in terms of their structure. Despite the lower efficiencies, the polymers showed superior reproducibility on each of the device parameters in comparison with the monomers and spiro-OMeTAD. Finally, star-shaped structures combine the advantages of both small molecules, like well-defined structures and physical properties, and polymers such as good thermal stability. Two star-shaped triarylamine-based molecules (Chapter 5) were synthesised, fully characterised and their function as hole-transport materials in perovskite solar cells studied. These materials afford a PCE of 13.63% and high reproducibility and device stability. In total this work provided three series of triarylamine-based hole transport materials for perovskite solar cells application and enabled a comparison of the pros and cons of different design structures: small-molecule, polymeric and star-shaped.

No description available.

No description available.

La conception des engrenages spiro-coniques reste encore très complexe de nos jours car la géométrie des dentures, et donc les performances cinématiques, découle du mode de fabrication de ce type d'engrenage. Le taillage est lié à deux constructeurs principaux : Gleason et Klingelnberg. De nombreux paramètres de réglage des machines influencent directement les surfaces de denture, leur optimisation n'est donc pas intuitive. Avec les progrès réalisés cette dernière décennie par les machines d'usinage à commande numérique et la FAO (Fabrication Assistée par Ordinateur), il devient possible de fabriquer des engrenages spiro-coniques de bonne qualité sur une machine 5 axes. Un modèle numérique a été développé pour générer une géométrie simplifiée de type Gleason, usinée par la suite avec une machine 5 axes. Une étude de métrologie, permettant de comparer les dents usinées avec les modèles CAO, a ensuite été réalisée pour prouver que l'usinage par une machine 5 axes peut être une alternative aux méthodes de taillage classiques. De nouveaux types de géométrie peuvent donc être proposés, qui ne pouvaient pas être envisagés par les moyens de fabrication classiques. Une géométrie basée sur la théorie des développantes sphériques, combinée à une spirale logarithmique a été développée, puis usinée. De plus, des corrections de bombé ou de profil peuvent être définies afin d'éviter les contacts en bords de denture. Ce type de géométrie analytique offre des possibilités plus simples d'optimisation de l'engrènement. L'optimisation des surfaces peut être réalisée à l'aide du modèle d'engrènement quasi-statique sous charge développé dans le cadre de cette thèse. L'environnement de l'engrenage est pris en compte dans la simulation : déformation des arbres, des dentures et de leurs supports (jantes et voiles) ainsi que les déformations locales de contact. La méthode des coefficients d'influence est utilisée pour résoudre le partage des charges entre toutes les dents instantanément en contact. Une méthode originale, utilisant sur un seul calcul élément finis et la définition de bases de fonctions, permet de calculer rapidement les flexions de denture dans leur environnement. Les déformations de contacts sont, quant à elles, obtenues par une méthode analytique, basée sur les théories de Boussinesq. De plus, des défauts d'assemblage peuvent être intégrés entre le pignon et la roue spiro-conique. Afin de valider les modèles numériques développés, un banc d'essai a été mis en place, permettant la mesure de l'erreur de transmission et la visualisation des portées. Le banc d'essai est intégré dans une fraiseuse numérique 3 axes : le pignon est monté dans la broche de la fraiseuse, le reste du banc étant bridé sur son plateau. Ainsi, des défauts de montage peuvent être appliqués facilement et précisément.

Energy from the sun can be converted to low cost electricity using dye-sensitized solar cells (DSCs). Dye molecules adsorbed to the surface of mesoporous TiO2 absorb light and inject electrons into the semiconductor. They are then regenerated by the reduced redox species from an electrolyte, typically consisting of the iodide/tri-iodide redox couple in an organic solvent. In a solid state version of the DSC, the liquid electrolyte is replaced by an organic hole conductor. Solid state DSCs using 2,2'7,7'-tetrakis-(N,N-di-p-methoxyphenyl-amine)-9,9'-spirobifluorene (spiro-MeOTAD) have reached conversion efficiencies of up to 6 %, which is about half of the efficiency of the best iodide/tri-iodide cells.   Measurement techniques, such as spectroelectrochemistry and photo-induced absorption spectroscopy (PIA), were developed and applied to study the working mechanism of organic dyes in solid state DSCs under solar cell operating conditions. The energy alignment of the different solar cell components was studied by spectroelectrochemistry and the results were compared to photoelectron spectroscopy. PIA was used to study the injection and regeneration processes. For the first time, it was shown here that the results of PIA are influenced by an electric field due to the electrons injected into the TiO2. This electric field causes a shift in the absorption spectrum of dye molecules adsorbed to the TiO2 surface due to the Stark effect.   Taking the Stark effect into consideration during the data analysis, mechanistic differences between solid state and conventional DSCs were found. A perylene dye, ID176, was only able to efficiently inject electrons into the TiO2 in presence of lithium ions and in absence of a solvent. As a result, the sensitiser worked surprisingly well in solid state DSCs but not in liquid electrolyte ones. Regeneration of oxidised dye molecules by spiro-MeOTAD was found to be fast and efficient and spiro-MeOTAD could even reduce excited dye molecules.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work describes firstly an efficient and regioselective method for the synthesis of a new series of 2,2,2-trifluoro-1-[4-methoxy-spiro(2H-chromen-2,1 -cycloalkan)-3-yl]ethanones from the Kabbe adducts (spiro[chroman-2,1 -cycloalkan]-4-ones). Yields of 38 % to 61 % were obtained when trifluoroacetylation reactions of mixtures of enolethers and/or acetals derived from four spiro ketones (Kabbe adducts) were performed at a temperature of 45 oC and employing anhydrous chloroform as the solvent. Subsequently, when the respective trifluoroacetylated Kabbe adducts reacted with phenylhydrazine and methylhydrazine at a 1:1 molar ratio in refluxing ethanol for 24 hours, a new series of seven examples of a novel spiro-condensed heterocyclic system, namely 1(2)-methyl(phenyl)-3-(trifluoromethyl)-1,4(2,4)-dihydro-spiro(chromen[4,3-c]pyrazole-4,n -cycloalkanes) where cycloalkanes are cyclopentane, cyclohexane and cycloheptane (n = 1) and tetrahydro-2H-pyran (n = 2) were isolated at yields of between 35 % and 51 %. NMR and X-ray diffraction techniques demonstrated clearly that reactions from methylhydrazine and phenylhydrazine were regioselective and allowed to isolate separately the 1,3- and 2,3-trifluoromethylated isomers, respectively. Subsequently, two examples of new 3-hydroxy-3-(trifluoromethyl)-3,3a-dihydro-4H-spiro(chromen[4,3-c]isoxazole-4,1 -cycloalkanes), derivated from cyclopentanone and cyclopentanone, were obtained from the reaction of 2,2,2-trifluoro-1-[4-methoxy-spiro(2H-chromen-2,1 -cycloalkan)-3-yl]ethanones with hydroxylamine hydrochloride in yields of 42% and 58%, respectively. Finally, the structures of new spiro heterocycles were determined with the aid and simultaneous application of 1H-, 13C{1H}- and 19F-NMR, X-ray monocrystal diffraction, Mass Spectrometry and DFT calculation techniques and their purity were proved by elemental analysis or High Resolution Mass Spectrometry (HRMS). / O presente trabalho descreve inicialmente um método eficiente e regiosseletivo para a síntese de uma nova série de 2,2,2-triflúor-1-[4-metóxi-espiro(2H-cromen-2,1 -cicloalcan)-3-il]etanonas a partir de adutos de Kabbe (espiro[croman-2,1 -cicloalcan]-4-onas). Rendimentos de 38% a 61% foram obtidos quando reações de trifluoracetilação de misturas de enoléteres e/ou acetais derivados de quatro espiro cetonas (adutos de Kabbe) foram realizadas a 45 ºC usando clorofórmio anidro como solvente. Subsequentemente, quando os respectivos adutos de Kabbe trifluoracetilados foram reagidos com fenilhidrazina ou metilhidrazina, em relação molar de 1:1, sob refluxo de etanol por 24 horas, uma série de sete exemplares de um novo sistema heterocíclico espiro-condensado, denominado 1(2)-metil(fenil)-3-(trifluormetil)-1,4(2,4)-diidro-espiro(chromen[4,3-c]pirazol-4,n -cicloalcanos) onde os cicloalcanos são ciclopentano, ciclohexano e cicloheptano (n = 1) e tetraidro-2H-pirano (n = 2), foi isolada em rendimentos entre 35 % e 51 %. Técnicas de RMN e de difração de raios-X demonstraram claramente que as reações a partir da metilhidrazina e da fenilhidrazina foram regiosseletivas e permitiram isolar separadamente os isômeros trifluormetilados 1,3 e 2,3, respectivamente. Em sequência, dois exemplares de novas 3-hidróxi-3-(trifluormetil)-3,3a-diidro-4H-espiro(cromen[4,3-c]isoxazol-4,1 -cicloalcanos), derivados da ciclopentanona e ciclohexanona, foram obtidos a partir da reação de 2,2,2-triflúor-1-[4-metóxi-espiro(2H-cromen-2,1 -cicloalcan)-3-il]etanonas com cloridrato de hidroxilamina em rendimentos de 42% e 58%, respectivamente. Finalmente, as estruturas dos novos espiro heterociclos foram determinadas com o auxílio e aplicação simultânea de experimentos de RMN de 1H, 13C{1H}, 19F, difração de raios-X em monocristais, Espectrometria de Massas e cálculos DFT e, a sua pureza comprovada por Análise Elementar ou por Espectrometria de Massas de Alta Resolução (HRMS).