Synthesis of spiroacetals using functionalised titanium carbenoids

Alkylidenation of lactones with functionalised titanium carbenoid reagents (Schrock carbenes) followed by acid-induced cyclisation of the resulting enol ethers constitutes a new method for the preparation of [4.4], [4.5] and [5.5] spiroacetals (1,6-dioxaspiro[4.4]nonanes, 1,6-dioxaspiro[4.5]decanes and 1,7-dioxaspiro[5.5]undecanes, respectively, sometimes termed 5,5-, 5,6- and 6,6-spiroketals). The titanium carbenoids are easily generated from readily available thioacetals

New methods for spiroketal synthesis

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Response of two tephritid species, Bactrocera oleae and Ceratitis capitata, to different emission levels of pheromone and parapheromone

Attractants and pheromones are commonly used in integrated pest management programs in crop systems. However, pheromone dispensers employed in monitoring traps and lure and kill devices are not usually well studied and attractants are released at uncontrolled rates leading to low treatment efficacies and misleading monitoring estimations. Fruit flies are pests of economic importance and monitoring is essential in order to program insecticidal treatments. Moreover, lure and kill techniques are being increasingly used, but the cost of these techniques depends on the number of required traps and, therefore, on the efficacy of the attractants. Ceratitis capitata and Bactrocera oleae are the two main fruit flies in Mediterranean countries, and the effect of different doses of trimedlure and spiroacetal on fly attraction has been studied. Results showed that a release rate over 1.28 mg/day of spiroacetal reduces B. oleae attraction and emission values over 2.4 mg of trimedlure per day did not increase C. capitata catches. Under the environmental conditions of our study, an optimum release rate for pheromone attraction in B. oleae was determined. Emission values over this optimum level reduced B. oleae attraction. However, when a parapheromone was used with C. capitata, a fruit fly of the same family, the optimum emission value was not found and higher quantities of parapheromone attracted the same number of flies. The saturation effect of high concentrations of pheromone and parapheromone is discussed.We wish to thank "Cartuja de Portacoeli" and Domingo de Guzman Orero for offering their orchards for this research, and Juan Bautista for field assistance. This research was supported by "Ministerio de Ciencia e Innovacion" project number AGL2006-13346-C02-02.Navarro Llopis, V.; Alfaro Cañamás, C.; Primo Millo, J.; Vacas González, S. (2011). Response of two tephritid species, Bactrocera oleae and Ceratitis capitata, to different emission levels of pheromone and parapheromone. Crop Protection. 30(7):913-918. https://doi.org/10.1016/j.cropro.2011.03.007S91391830

Synthesis and Biological Evaluation As Microtubule-Active Agents of Several Tetrahydrofuran and Spiroacetal Derivatives

The stereoselective preparation of several molecules containing structural fragments of the tetrahydrofuran and spiroacetal type is described. Their degree of cytotoxicity and their interactions with tubulin have been investigated. It has been confirmed that the tetrahydrofuran derivatives are cytotoxic but, in contrast to previous reports, it has been found that the cytoxicity is not due to interactions with the microtubule network. Furthermore, and also in contrast to a previous report on closely related compounds, the spiroacetal derivatives do show interactions with tubulin, even though the precise mechanism and the binding site still remain to be established

Polyamides based on a partially bio-based spirodiamine

In this study novel, fully and partially bio-based polyamides containing spiroacetal moieties in the backbone derived from bio-glycerol and bio-ethanol were prepared and characterized. The renewable diamine employed to obtain a series of polyamides was synthesized by means of thiolene click chemistry and therefore contains flexible thioether as well as rigid spiroacetal moieties. Two different chemical pathways for the polymerization were investigated and evaluated. The polymerization of polyamide salts proved to be the most promising method and therefore salt polymerization was applied in the synthesis of polyamides with aliphatic and aromatic di-carboxylic acids. Subsequently, the structure of the polymers was confirmed by Maldi-ToF analysis and additionally thermal and mechanical properties were investigated revealing T-g's between 24 and 80 degrees C and ductile materials with moduli between 1.0 and 1.5 GPa. Both semicrystalline and amorphous polyamides were thermally stable and therefore suitable for thermal processing. In the end, degradation studies were performed on the acetal containing polyamides which showed that the polymers were stable at pH 3 and higher

Toward Biomass-Derived Recyclable Polyesters

Fossil-based plastics have become a matter of concern due to their negative environmental impacts such as greenhouse gas emissions and threats to the health of living beings. Alternative polymers derived from sustainable biomass resources have thus become an attractive research field since the last decade. Currently, there is a strong demand in the development of new bio-based polymers with enhanced properties (e.g., thermal, mechanical, and barrier properties) and recycling possibilities. This thesis focuses on the design and synthesis of various monomers and polymers using bio-based starting molecules, particularly those derived from lignin fragments such as vanillin. Attention was paid to unravel the impacts of certain molecular structures such as spirocyclic acetals on the polymer properties and recyclability. This thesis includes five papers that describe the important findings of various bio-based polyesters. In Papers I, II, and III, diol and dicarboxylate ester monomers with spirocyclic acetal structures have been synthesized by coupling vanillin with pentaerythritol and derivation by SN2 reactions. Preliminary life cycle assessment (LCA) results indicated that the production of the diol monomer with spiroacetal structures generates low greenhouse gases (Paper I). This diol monomer was used to synthesize copolyesters together with dimethyl terephthalate and 1,6-hexanediol (Paper I) and neopentyl glycol (Paper II). The glass transition temperatures of these polyesters were significantly enhanced by the incorporation of the spiroacetal monomeric units in the backbone. Furthermore, the spiroacetal units could be selectively cleaved under mild acidic conditions, yielding telechelic polymers with aldehyde end groups (Paper II). The resulting telechelic polymers could be conveniently converted back to the original polymers by polyacetalization with pentaerythritol, which showed their potential in the development of a new energy efficient chemical recycling process. We have also demonstrated that polyesters with spiroacetal units could be effectively hydrolyzed using an enzyme Humicola insolens cutinase, which suggested its potential in enzymatic recycling or biodegradation (Paper III). The effectiveness of the same enzyme on a commercial polyester with spiroacetal units (AkestraTM, Paper IV), as well as newly synthesized methoxyhydroquinone-based polyesters without spiroacetal units (Paper V), was also demonstrated

Asymmetric Brønsted Acid Catalysis: Acetals & Confined Catalysts

The developments of Brønsted acid catalyzed asymmetric syntheses of acetals and a novel class of confined Brønsted acid catalysts are described. The first highly enantioselective intramolecular transacetalization reaction catalyzed by the chiral BINOL-derived phosphoric acid TRIP was developed to access chiral acetals with the acetal carbon as the only stereogenic center. The practical utility of the catalytic asymmetric transacetalization reaction was demonstrated in a kinetic resolution of homoaldol acetals. Both secondary and tertiary homoaldols were resolved with high enantioselectivity using phosphoric acid STRIP based on a 1,1′-spirobiindane backbone. The first catalytic asymmetric spiroacetalization reaction was developed, enabling access to small unfunctionalized spiroacetal compounds, including the natural product olean, which possesses a spiroacetal center as the only source of chirality. In addition, the catalyst controlled access to thermodynamic and nonthermodynamic spiroacetals was achieved offering a solution to this long standing issue in synthesis of spiroacetal natural products. Most significantly, to enable the spiroacetalization reaction a novel class of chiral Brønsted acids, termed confined Brønsted acids was designed and developed. Confined Brønsted acids based on a C2-symmetric imidodiphosphate anion feature an extremely sterically demanding chiral microenvironment with a single catalytically relevant and geometrically constrained bifunctional active site. This catalyst design is expected to find wide utility in various asymmetric reactions involving small and functionally unbiased substrates

Linoleic Acid Promotes Emission of Bark Beetle Semiochemicals by Fungal Symbionts

Tree-killing bark beetles in conifer forests vector symbiotic fungi that are thought to help the beetles kill trees. Fungal symbionts emit diverse volatile blends that include bark beetle semiochemicals involved in mating and host localization. In this study, all 12 tested fungal isolates emitted beetle semiochemicals when growing in medium amended with linoleic acid. These semiochemicals included the spiroacetals chalcogran, trans-conophthorin and exo-brevicomin, as well as 2-methyl-3-buten-1-ol, the main aggregation pheromone component of the spruce bark beetle Ips typographus. The emission of these compounds was affected by the type of fatty acid present (linoleic vs. oleic acid). Accumulating evidence shows that the fatty acid composition in conifer bark can facilitate colonization by bark beetles and symbiotic fungi, whereas the fatty acid composition of non-host trees can be detrimental for beetle larvae or fungi. We hypothesize that beetles probe the fatty acid composition of potential host trees to test their suitability for beetle development and release of semiochemicals by symbiotic fungi.publishedVersio

Marine heterocyclic compounds that modulate intracellular calcium signals: Chemistry and synthesis approaches

Producción CientíficaIntracellular Ca2+ plays a pivotal role in the control of a large series of cell functions in all types of cells, from neurotransmitter release and muscle contraction to gene expression, cell proliferation and cell death. Ca2+ is transported through specific channels and transporters in the plasma membrane and subcellular organelles such as the endoplasmic reticulum and mitochondria. Therefore, dysregulation of intracellular Ca2+ homeostasis may lead to cell dysfunction and disease. Accordingly, chemical compounds from natural origin and/or synthesis targeting directly or indirectly these channels and proteins may be of interest for the treatment of cell dysfunction and disease. In this review, we show an overview of a group of marine drugs that, from the structural point of view, contain one or various heterocyclic units in their core structure, and from the biological side, they have a direct influence on the transport of calcium in the cell. The marine compounds covered in this review are divided into three groups, which correspond with their direct biological activity, such as compounds with a direct influence in the calcium channel, compounds with a direct effect on the cytoskeleton and drugs with an effect on cancer cell proliferation. For each target, we describe its bioactive properties and synthetic approaches. The wide variety of chemical structures compiled in this review and their significant medical properties may attract the attention of many different researchers.Ministerio de Ciencia e Innovación - (grant RTI2018-099298-B-100)Junta de Castilla y León - (grant VA294-P18

Studies on the Natural Products (±)-Lingzhiol and Gulmirecin B

This thesis contains several independent projects, covering two aspects of organic chemistry: natural product synthesis and investigation of new synthetic methodology. The first chapter contains the total synthesis of (±)-Lingzhiol, derivatives and their biological evaluation. The second chapter describes efforts towards the total synthesis of Gulmirecin B. The third chapter is about Spiroacetal formation by photocatalysis