Catalytic Cage Formation via Controlled Dimerization of Norbornadienes: An Entry to Functionalized HCTDs (Heptacyclo­[6.6.0.0^2,6.0^3,13.0^4,11.0^5,9.0^10,14]­tetradecanes)

A general and practical catalytic method has been developed for the rapid synthesis of HCTD (heptacyclo­[6.6.0.0^2,6.0^3,13.0^4,11.0^5,9.0^10,14]­tetradecanes) and various new 7,12-disubstituted HCTDs from norbornadienes. Compared to the known approaches, this new protocol avoids stoichiometric metals, utilizes commercially available reagents as catalysts, and affords higher yields and significantly improved selectivity. In addition, quadracyclane was discovered for the first time to undergo a similar <i>endo</i>,<i>cis</i>,<i>endo</i> cycloaddition to give HCTD in a good yield. Derivatization of HCTDs led to efficient preparation of a range of novel homo- and heterobifunctional scaffolds that hold potentials for biological and material applications

Methyl Pyruvate Oxime as a Carbonyl Synthon: Synthesis of Ureas, Carbamates, Thiocarbamates, and Anilides

A new strategy for the synthesis of unsymmetrical ureas, carbamates, thiocarbamates, and anilides was developed with methyl pyruvate oxime as the carbonyl synthon. The intrinsic reactivity of the reagent enabled consecutive disubstitution involving direct amidation and one-pot deoximative substitution with various nucleophiles. The utility of the method was demonstrated with the synthesis of bioactive molecules

Intermolecular Radical Cation Diels–Alder (RCDA) Reaction of Bicyclooctadienes: Biomimetic Formal Total Synthesis of Kingianin A and Total Syntheses of Kingianins D, F, H, and J

Three endo bicyclooctadienol dimers corresponding to kingianins A and H, D, and F and J were obtained by the intermolecular radical cation Diels–Alder (RCDA) reaction. Each isomer was cleanly isolated without the aid of preparative HPLC. Kingianins D, F, H, and J were prepared by way of these intermediates from commercially available materials in 10, 13, 9, and 17 steps, respectively. Kingianin A has already been prepared from one of these compounds. Completion of the synthesis of kingianin H relied on Manchand’s one-step, three-carbon homologation

Total Synthesis of Kingianin A

A 12-step synthesis of kingianin A, an inhibitor of the antiapoptotic protein Bcl-xL, is based on a radical cation Diels–Alder reaction (RCDA). This approach is thought to be biomimetic. The use of a tether in the key RCDA step controls the regiochemistry of the cycloaddition, leading to the desired core structure and a separable diastereomer

Total Synthesis of Kingianin A

A 12-step synthesis of kingianin A, an inhibitor of the antiapoptotic protein Bcl-xL, is based on a radical cation Diels–Alder reaction (RCDA). This approach is thought to be biomimetic. The use of a tether in the key RCDA step controls the regiochemistry of the cycloaddition, leading to the desired core structure and a separable diastereomer

Etude de ressources végétales tropicales pour un usage anthelminthique en élevage de ruminants

Gastrointestinal parasitism (GI) is a major health and welfare problem of farmed ruminants. It affects animal health and has a negative impact on overall productivity of herds. Since the 1960s, chemotherapy is the principal means of nematode control. However, the emergence of resistance of strongyles to chemical anthelmintics has become a widespread phenomenon in the world. These factors led the search to consider alternative solutions to fight against GI parasites of ruminants. This thesis is part of the scientific program of the INRA - URZ unit on multicriteria evaluation of plant resources and integrated management against GI parasites of ruminants. Integrated management combines several control methods including herbal medicines. The objective of this thesis is to investigate the nematicidal activity of some plant resources against the Haemonchus contortus digestive strongyles, and secondly to characterize the chemical class responsible for the activity and then to explain the mode of action. In a first part , a literature survey of plant resources available in the Antilles - Guyane for health use has been made. This has shown that these regions have a veritable arsenal of plants for a wide range of pathologies. A screening for in vitro egg hatching and larval development with the model H. contortus was then performed on 14 plants, all showed anthelmintic effect on at least one stage. The efficie ncy varies between 20% and 55% on the hatching of eggs, and 26% to 98% for larval development. In a second part , the 4 plants: Cucurbita moschata, Tabernaemontana citrifolia, Musa x paradisiaca and Manihot esculenta, were selected in relation to diversity in secondary metabolites of interest that they contain: condensed tannins, flavonoids, lkaloids, amino compounds, terpenoids, to carry out in vitro tests. The in vitro targeting the 4 key developmental stages: egg hatching, development of L1 to L2, L3 lar val migration and motility of adult worms. These plants have all shown a nematicidal action with variations depending on the stage, highlighting the specificity of the molecules with respect to parasitic stages. Thus, indole alkaloids act on the 4 stages, flavonoids and terpenoids affect the adult stage, while condensed tannins, amino compounds, flavonoids and terpenoids have an impact on the larval development. In a third part , both models banana (Musa x paradisiaca ) and cassava leaves ( Manihot esculenta) were evaluated in vivo . In addition to their potential nutritional and nematicidal effects, these two resources have the interest to allow recovery of co-products from agricultural crops. The involvement of condensed tannins from cassava was confirmed by the use of PEG as a specific inhibitor. Effects on the installation of infective larvae (only for cassava), on the fertility of female worms and on the larval development were observed (both plants). In conclusion, these studies show first, that plant resources are a real alternative to synthetic anthelmintics, and secondly, the interest to combine phytochemical knowledge with zootechnical knowledge, particularly in order to develop the concept of nutriceuticals. The solution for the control of GI strongyles by limiting the use of anthelminthic chemicals seems to be integrated management, with a multi-criteria approach in which the herbal take a share. For this it is necessary to standardize research on antiparasitic plants (in vitro methods, threshold values for the active antinutrutional factors). A comprehensive approach taking into account not only the antiparasitc potential, the immunomodulator potential and nutrition but also the economic criterion, would incorporate the best plant resources in livestock production systems in order to improve the level of production while reducing agricultural inputs

C–C Bond Cleavage-Induced C- to N‑Acyl Transfer for Synthesis of Amides

A new approach for the preparation of amides was developed using C–C bond cleavage that initiates C- to N-acyl transfer, employing activated ketones as acylation reagents and amine nucleophiles. The reaction was operational under the coupling reagent system that is commonly utilized for peptide bond formations. The method enables practical preparation of amides using linear and cyclic ketone substrates under mild conditions