Improved Access to Chiral Tetranaphthoazepinium-Based Organocatalysts Using Aqueous Ammonia as Nitrogen Source.

The class of 3,3'-diaryl substituted tetranaphthobisazepinium bromides has found wide application as highly efficient C2-symmetrical phase-transfer catalysts (PTCs, Maruoka type catalysts). Unfortunately, the synthesis requires a large number of steps and hampers the build-up of catalyst libraries which are often desired for screening experiments. Here, we present a more economic strategy using dinaphthoazepine 7 as the common key intermediate. Only at this stage various aryl substituents are introduced, and only two individual steps are required to access target structures. This protocol was applied to synthesize ten tetranaphthobisazepinium compounds 1a-1j. Their efficiency as PTCs was tested in the asymmetric substitution of tert-butyl 2-((diphenylmethylene)amino)acetate. Enantioselectivities up to 92% have been observed with new catalysts.

Economy of Catalyst Synthesis-Convenient Access to Libraries of Di- and Tetranaphtho Azepinium Compounds.

Efficient optimization procedures in chiral catalysis are usually linked to a straightforward strategy to access groups of structurally similar catalysts required for fine-tuning. The ease of building up such ligand libraries can be increased when the structure-modifying step (introduction of a substituent) is done at a later stage of the synthesis. This is demonstrated for the extended family of di- and tetranaphtho azepinium compounds, widely used as chiral phase transfer catalysts (PTC). Using 2,6-diiodo-4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]azepine and 4,8-diiodo-6,7-dihydro-5H-dibenzo[c,e]azepine, respectively, as key intermediates, 18 spiro-azepinium compounds were synthesized in a total yield of 25-42% over 6-7 steps from 1,1'-binaphthyl-2,2'-dicarboxylic acid or diphenic acid, respectively. The replacement of iodo groups with aryl substituents was performed as the last or the penultimate step of the synthesis.

Fluorescent molecular rotors as versatile in situ sensors for protein quantitation.

Accurate protein quantitation is essential for many cellular mechanistic studies. Existing technology relies on extrinsic sample evaluation that requires significant volumes of sample as well as addition of assay-specific reagents and importantly, is a terminal analysis. This study exploits the unique chemical features of a fluorescent molecular rotor that fluctuates between twisted-to-untwisted states, with a subsequent intensity increase in fluorescence depending on environmental conditions (e.g., viscosity). Here we report the development of a rapid, sensitive in situ protein quantitation method using ARCAM-1, a representative fluorescent molecular rotor that can be employed in both non-terminal and terminal assays.

Insecticidal and growth inhibitory effects of some thymol derivatives on the beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae) and their impact on detoxification enzymes.

BACKGROUND: Thymol is a known natural product with insecticidal activity against several insect species. A recent study on structural modifications of thymol to thymyl esters and their efficacy against Spodoptera litura suggested that such an approach could develop generalized novel insecticides/insect growth inhibitors and requires further studies to establish the efficacy against lepidopterans. RESULTS: Thymol and structurally modified eight esters were evaluated against beet armyworm, Spodoptera exigua using the topical application. Thymyl butanoate was the most toxic compound with a median lethal dose (LD50 ) of 2.33 and 1.62 µg/larva after 24 and 48 h posttreatment, respectively. All thymyl esters were potentially better than the parent compound thymol, except thymyl dibromoacetate, in their efficacy against Spodoptera exigua. Essentially, there were three levels of activity vis-à-vis the compounds used, that is, with the LD50 range of 1.5 to 5.0, 7.0 to 15.0, and > 20 µg/larva, respectively. Ovicidal activity and reduction in larval growth were also determined by treating third instars at sub-lethal doses, that is, LD50 doses of second instars. Thymyl butanoate treated larvae inhibited glutathione S-transferase, carboxylesterase, and acetylcholinesterase activities, whereas the other thymyl esters induced these enzymes. CONCLUSION: Thymyl butanoate exhibited higher toxicity against Spodoptera exigua and is the first to report about > 15.5× more toxicity than thymol and > 6.5× than thymyl cinnamate, which suggests that the efficacy was species-specific versus the chemical structural variation of the esters. © 2021 Society of Chemical Industry.

Synthesis of thymyl esters and their insecticidal activity against Spodoptera litura (Lepidoptera: Noctuidae).

BACKGROUND: Thymol, a natural phenolic monoterpene originating from Thymus vulgaris, is recognized as a safe and potent botanical insecticide to many insects. The structural modification of thymol into thymyl esters is a potential approach for the development of novel insecticides, which showed more toxicity than thymol. However, there are no reports on the insecticidal activity of thymyl esters to control Spodoptera litura. RESULTS: Thymol was structurally modified into ten thymyl esters by esterification using a new reagent, PPh3 /Br3 CSO2 Ph. The insecticidal activity of these compounds was examined against the second instars of Spodoptera litura using a topical application. Among the ten thymyl esters evaluated, thymyl cinnamate was the most toxic with LD50  = 0.41 and 0.34 µg/larva after 24 and 48 h posttreatment, respectively. In addition, thymyl cinnamate-treated larvae showed increasing carboxylesterase and acetylcholinesterase activities in vivo experiment, whereas glutathione S-transferase activity showed no significant difference. CONCLUSION: Thymyl cinnamate were first reported to exhibit toxicity against S. litura 2.41-2.46 fold more efficient than thymol. However, the detailed biochemical interactions are necessary for further development of novel insecticides. © 2019 Society of Chemical Industry.