Fonctionnalisation directe de liaisons C-H et couplages croisés pour la formation de liaisons C-C et C-N (synthèse de purines 6,8,9-trisubstituées)

La grande variété de propriétés biologiques associées au noyau purine en fait une structure privilégiée pour la conception et la synthèse de nouvelles molécules à visée thérapeutique. Cette spécificité est étroitement liée à la grande diversité de substituants pouvant être introduits sur les différentes positions du noyau purine et en particulier sur C2, C6, C8 et N9. Par conséquent, le développement de méthodes de fonctionnalisation rapides de cette famille de composés est d un grand intérêt synthétique. Nous nous sommes focalisés sur la formation de liaisons C-C et C-N sur les positions 6 et 8 du noyau purine pour pouvoir présenter de nouveaux outils de synthèse permettant d introduire une plus grande diversité fonctionnelle. D une part, nous avons étudié la fonctionnalisation directe de liaisons C-H de purines, sujet encore peu exploré. En effet, de nos jours, le traditionnel couplage croisé (Negishi, Suzuki-Miyaura), utilisé pour la création de liaisons C-C, se voit de plus en plus concurrencé par ces réactions puisqu elles ne nécessitent pas la préparation d un partenaire organométallique. Ce sont des réactions dites à économie d atomes. En nous basant sur l expérience du laboratoire dans le domaine de la fonctionnalisation directe de liaisons C-H, nous avons envisagé l alcénylation et l alcynylation directes en position 8 de la purine, les motifs alcényle et alcynyle étant présents dans certaines purines d intérêt biologique. D autre part, nous nous sommes intéressés à deux méthodes de couplage croisé pallado-catalysé permettant la formation de liaisons C-N et C-C : le couplage de Buchwald Hartwig entre une 8-iodopurine et des amides ou des amines aromatiques, et le couplage de Liebeskind Srogl entre une 6-thioétherpurine et divers acides boroniques.Purine is the most widely distributed N-heterocycle scaffold in the nature and its derivatives are well known for their biological and fluorescent properties. These characteristics are linked to the diversity of substituents that can be introduced, especially on the C-2, C-6, C-8 and N-9 positions. Therefore, the development of methods for rapid functionalization of this family of compounds represent a valuable asset. We focused on the formation of C-C and C-N bonds at positions 6 and 8 of the purine ring in order to provide new synthesis tools allowing the introduction of functional diversity. On the one hand, we studied the direct functionalization of C-H bonds of purines, subject still little explored. Indeed, nowadays, traditional cross-coupling reactions (Negishi, Suzuki-Miyaura), used for the creation of C-C bonds, are increasingly challenged by these reactions since they do not require the preparation of an organometallic partner. Their advantage lies in step and atom economy. Based on previous experience in our laboratory in the field of direct functionalization of C-H bonds, we envisioned direct alkenylation and alkynylation at position 8 of the purine, knowing that alkenyl and alkynyl patterns are found in purines of biological interest. On the other hand, we were interested in two pallado-catalyzed cross-coupling methods for the formation of C-N and C-C bonds : Buchwald Hartwig coupling between 8-iodopurine and aromatic amines or amides, and Liebeskind Srogl coupling between 6-thioétherpurine and a range of boronic acids.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Oxazole Dyes With Potential For Photoluminescence Bioprobes: A Two-Photon Absorption Study

In this work, six π-conjugated oxazole compounds dissolved in dichloromethane were characterized with linear and nonlinear optical measurements. Z-scan with femtosecond laser pulses was employed to determine the two-photon absorption (TPA) spectra. Other photophysical parameters, such as absorbance, solvatochromism, lifetime fluorescence, and fluorescence anisotropy, were evaluated with linear optical techniques. The experimental TPA cross section spectra were adjusted by the sum-over-states (SOS) model, by which important parameters such as transition dipole moments and broadening parameters were determined. To better understand the TPA spectra of the oxazole compounds, quantum-chemical calculations using the response function formalism and the density functional theory level of theory were performed. Using the results provided by the quantum-chemical calculations and the broadening parameters estimated through the application of the SOS model, the TPA spectra were simulated by the superposition (summation) of individual homogeneous Lorentzian absorption profiles

Arylation, alcénylation et alcynylation directes d'azoles et conception et synthèse d'inhibiteurs de la polymérase du virus de la dengue

ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Direct Alkynylation of 3<i>H</i>‑Imidazo[4,5‑<i>b</i>]pyridines Using <i>gem</i>-Dibromoalkenes as Alkynes Source

C2 direct alkynylation of 3<i>H</i>-imidazo­[4,5-<i>b</i>]­pyridine derivatives is explored for the first time. Stable and readily available 1,1-dibromo-1-alkenes, electrophilic alkyne precursors, are used as coupling partners. The simple reaction conditions include an inexpensive copper catalyst (CuBr·SMe₂ or Cu­(OAc)₂), a phosphine ligand (DPEphos) and a base (LiO<i>t</i>Bu) in 1,4-dioxane at 120 °C. This C–H alkynylation method revealed to be compatible with a variety of substitutions on both coupling partners: heteroarenes and <i>gem</i>-dibromoalkenes. This protocol allows the straightforward synthesis of various 2-alkynyl-3<i>H</i>-imidazo­[4,5-<i>b</i>]­pyridines, a valuable scaffold in drug design

Three-component C-H bond sulfonylation of imidazoheterocycles via visible-light organophotoredox catalysis

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Photoactivatable Small‐Molecule Inhibitors for Light‐Controlled TAM Kinase Activity

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Microwave-Assisted Pd/Cu-Catalyzed C-8 Direct Alkenylation of Purines and Related Azoles: An Alternative Access to 6,8,9-Trisubstituted Purines

An efficient microwave-assisted palladium/copper comediated C-8 direct alkenylation of purines with styryl bromides has been developed. The method is regioselective, functional group tolerant, rapid, and compatible with other related azoles. Combined with subsequent nucleophilic substitution, it provides an easy access to new 6,8,9-trisubstituted purines

New aminopyrimidine derivatives as inhibitors of the TAM family

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