The regioselective lithiation of dithienothiazines followed by electrophilic trapping in a one-pot fashion is an efficient route to 2-mono-and 2,6-difunctionalized dithienothiazines. A pseudo five-component dilithiation-diformylation-double-Wittig olefination sequence gives a dithienothiazine symmetrically functionalized with α,β-unsaturated ester side chains in excellent yield.In recent years, interest in electroactive organic molecules has increased enormously because of their important technological applications, ranging from organic light-emitting diodes 1 through organic photovoltaic devices 2 to organic field-effect transistors. 3 The main advantages of using organic materials are their low production costs; their favorable properties, such as flexibility, transparency, and light weight; and their good processability.We recently described dithienothiazines as a new class of electron-rich heterocycles. 4 As a consequence of their unique electronic properties, which show two reversible oxidations with Nernstian behavior at low oxidation potentials, dithienothiazines are well suited, in principle, for use as hole conductors or as donor components in donoracceptor compounds. Functionalization of the heterocyclic core of dithienothiazines represents a key step to achieving potential applications of these compounds, and is a major challenge. Most interestingly, annelation of thiophene offers an easy entry to typical thiophene transformations, such as lithiation in the α-position with respect to the sulfur atom; 5 furthermore, it is also amenable to sequential one-pot processing. 6 Here, we report a practical scale-up of the synthesis of three selected N-substituted dithienothiazines, together with the functionalization of this new class of electron-rich heterocycles through dilithiation and electrophilic trapping.We examined the scale-up of the intermolecular/intramolecular Buchwald-Hartwig synthesis of 4-phenyl-4H-dithieno[2,3-b:3′,2′-e][1,4]thiazine (3a) from bis(3-bromo-2-thienyl) sulfide (1) and aniline (2a). Linear scale-up from 0.5 to 3 mmol was uneventful (Scheme 1). Furthermore, we were able to reduce the catalyst loading to 5 mol% and the ligand loading to 10 mol% without any decrease in yield. Besides aniline (2a), hexan-1-amine (2b) was successfully used as an amine component, albeit with a lower yield of the corresponding dithienothiazine 3b. Nevertheless, the introduction of a solubilizing hexyl group is very attractive. Therefore, by combining a hexyl substituent with the higher yield of aniline derivatives, we successfully introduced a 4-hexylphenyl substituent in the dithienothiazine 3c.Scheme 1 Synthesis of selected dithienothiazines 3 by twofold Buchwald-Hartwig coupling Next we tested several methods for functionalizing dithienothiazines by exploiting the inherent reactivity of thiophenes. However, attempted bromination with bromine or N-bromosuccinimide as brominating reagent 5a to give 2,6-dibromodithienothiazines failed in a range of solvents and at various reaction temperatures. As a last r...
The DNA damage response (DDR) is a complex set of downstream pathways triggered in response to DNA damage to maintain genomic stability. Many tumours exhibit mutations which inactivate components of the DDR, making them prone to the accumulation of DNA defects. These can both facilitate the development of tumours and provide potential targets for novel therapeutic interventions. The inhibition of the DDR has been shown to induce radiosensitivity in certain cancers, rendering them susceptible to treatment with radiotherapy and improving the therapeutic window. Moreover, DDR defects are a strong predictor of patient response to immune checkpoint inhibition (ICI). The ability to target the DDR selectively has the potential to expand the tumour neoantigen repertoire, thus increasing tumour immunogenicity and facilitating a CD8+ T and NK cell response against cancer cells. Combinatorial approaches, which seek to integrate DDR inhibition with radiotherapy and immunotherapy, have shown promise in early trials. Further studies are necessary to understand these synergies and establish reliable biomarkers.
Bioactivity-guided fractionation was used to isolate two compounds, tomentosenol A (1) and torellianone A (2), from a cerumen extract from Tetragonula carbonaria. The anti-fibrotic activity of these compounds was examined using human cultured neonatal foreskin fibroblasts (NFF) and immortalised keratinocytes (HaCaTs). Tomentosenol A (1), inhibited NFF and HaCaT cell proliferation and prevented NFF and HaCaT scratch wound repopulation at 12.5–25 µM concentrations. These inhibitory effects were associated with reduced cell viability, determined by tetrazolium dye (MTT) and sulforhodamine B (SRB) assays. Compound 1 further inhibited transforming growth factor-β1 (TGF-β1)-stimulated, NFF-myofibroblast differentiation and soluble collagen production; and was an effective scavenger of the model oxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH·), with an EC50 value of 44.7 ± 3.1 µM. These findings reveal significant anti-fibrotic potential for cerumen-derived tomentosenol A (1).
Four bis(dioxane) adducts of mixed‐metal trifluoroacetates, M[M′(O2CCF3)4(C4H8O2)2] (M = Na, K, Cs, M′ = In and M = Cs, M′ = Ga) were synthesized by reaction of alkali metal trifluoroacetate and group 13 element trifluoroacetate in 1,4‐dioxane and completely characterized including X‐ray structure determination. Geometric parameters, empirical bond valences and frequencies of the symmetric C=O stretching vibrations show that the moisture sensitive solids are composed of dimeric structural moieties with site symmetry 1, containing alkali metal ions and bis(dioxane)tetrakis(trifluoroacetato)indate or ‐gallate ions. The dimeric units are further connected by weaker “intermolecular” dioxane interactions to neighboring alkali metal ions. Closer inspection of space group symmetry, unit cell parameters and atom sites allows to rationalize the compounds as members of two isotypic pairs that are further closely related due to the group‐subgroup relation of their monoclinc space groups to a common orthorhombic supergroup.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.