Photocatalytic Carbamoyl Radical Transfer to Alkenyl Azaarenes

1-Phenyl-3-azaarenyl-propan-1-amine structural moieties have been widely incorporated in pharmaceuticals and biologically active compounds; however, current synthetic methods to access these compounds need multiple steps and proceed with low efficiency. Herein, we reported an efficient photocatalytic carbamoyl radical transfer approach that allows the preparation of these compounds in high yields (up to 88%). The reaction easily runs on a gram-scale and was applied for the preparation of pheniramine in two steps with 72% total yield.

Chemical Synthesis and Antitumor Evaluation of Chikusetsusaponin IVa Butyl Ester and Its Analogues

Chikusetsusaponin IVa butyl ester (CS-IVa-Be) is a triterpene saponin that acts as a novel IL6R antagonist for inducing breast cancer cell apoptosis. However, the structure–activity relationship for this class of saponins remains unclear. Here, we report a gram-scale synthesis of CS-IVa-Be and the efficient preparation of eight of its analogues. CS-IVa-Be was demonstrated to have significant antitumor activities against MDA-MB-231, HepG2, and A549 cells. When one of the sugar residues at either the 3-OH or 28-COOH position of CS-IVa-Be was cleaved, or the length of the alkyl chain on the d-glucuronic acid residue of CS-IVa-Be was changed, these analogues showed varied inhibitory activities against the cancer cell lines. Notably, the carboxylic acid form of CS-IVa-Be exhibited a stronger antitumor activity against MDA-MB-231 cells. Furthermore, the carboxylic acid form of CS-IVa-Be inhibited MDA-MB-231 cell proliferation in a dose-dependent manner by arresting the cell cycle at the G2/M phase.

Adventures in Coumarin Chemistry

The cyclization of various nucleophiles, such as 1,3-dicarbonyl compounds, 1,3-bis(silyloxy)-1,3-butadienes, hydrazones, hydroxylamine, amidines, thioglycolic esters, heterocyclic enamines and others, with 4-chlorocoumarins, containing an electron-withdrawing group at position 3, allows for a convenient synthesis of a great variety of benzo[c]coumarins and related fused coumarins. Suzuki–Miyaura reactions of coumarin-derived bis(triflates) result in formation of arylated coumarins with excellent regioselectivity that is controlled by electronic and steric features of the substrate. The combination of Suzuki–Miyaura with lactonization reactions of carba- and heterocyclic substrates allows for the synthesis of benzo[c]coumarins and of other fused coumarins. Domino Michael–retro-Michael–lactonization reactions of 1,3-bis(silyloxy)-1,3-butadienes with chromones provide a convenient access to hydroxylated benzo[c]coumarins. In a related approach, fused coumarins were prepared by domino reactions of heterocyclic enamines with chromone-3-carboxylic acids.1 Introduction2 Reactions of 3-Acceptor-4-chlorocoumarins3 Reactions of Coumarin Triflates4 Synthesis of Fused Coumarins5 Conclusions

Regioselective Aldehyde Decarbonylation through Palladium-Catalyzed Nitrile Boronic Acid Cross-Coupling

Aldehyde decarbonylation is a vital chemical transformation in the synthesis of natural products. Nature accomplishes this process through a family of decarbonylase enzymes, while in the laboratory, harsh transition metals and elevated temperatures are required. Herein, we report a mild aldehyde decarbonylation reaction that exhibits exclusive selectivity for ortho-aldehydes during a tandem nitrile boronic acid cross-coupling reaction. A wide substrate scope is displayed that includes regioselective removal of the ortho-aldehyde from phenyl boronic acids in the presence of meta- or para-aldehydes. A mechanistic investigation of the observed regioselectivity for ortho-aldehydes by density functional theory (DFT) calculations shows that the CO ligand extrusion is energetically more favorable for the ortho position as compared to the para position.

Synthesis and α-Functionalisation of Cyclic Imines

α-Functionalisation of cyclic imines is explored. The cyclic imine substrates are synthesised from their respective halonitrile precursors using a nucleophilic addition/cyclisation sequence. Selective monohalogenation of the cyclic imines yields α-haloimines, which serve as a platform to obtain various α-hydroxyimine derivatives. In addition, an unusual tautomerisation and oxidation sequence is observed in the attempted preparation of α-hydroxyimines.

Palladium-Catalyzed Carbothiolation by Using Thioesters with Formation of a Quaternary Carbon

A Pd-catalyzed carbothiolation using thioesters, with the formation of a quaternary carbon, is described. Carbothiolation using thioesters was problematic due to a direct-coupling side reaction that produced a sulfide, but this side reaction was successfully suppressed by an appropriate selection of the thioester and the reaction conditions. In the preparation of chroman or coumaran derivatives by this method, the reaction using S-phenyl 4-methoxybenzenecarbothioate Pd(PPh3)4, and Cs2CO3 at 100 °C in toluene afforded the desired products in good yields (77–92%). The carbothiolation reaction also proceeded with esters of alkanethiols in higher yields (56–93%) than those obtained from the previously reported carbothiolation using triisopropylsilyl (TIPS) thioethers (12–63%). The developed Pd-catalyzed carbothiolation is applicable in the preparation of a wide range of products, including a tetralin derivative and an indoline derivative. The Pd-catalyzed carbothiolation using thioesters was found to be comparable with a previously reported carbothiolation using TIPS thioethers in terms of the yield and substrate scope, and to be a superior alternative owing to the stability and lower cost of thioesters.

Polydiacetylene Micelles in Nanomedicine and Beyond

In this account article, we give an overview of our contribution to the development of stable micellar carriers obtained by self-assembly and photo-polymerization of diacetylenic amphiphiles. The stabilized micelles can be loaded with active substances and used for diagnostic and therapeutic applications, or loaded with a metal catalyst to promote some synthetic transformations in fully aqueous medium.Table of content1 Introduction2 Polydiacetylene Micelles Applied to Nanomedicine2.1 From Amphiphilic Units to Micelles2.2 In vivo Behavior of Micelles2.3 Passive Targeting of Tumors with Micelles2.4 Drug Delivery with Micelles2.5 Towards Improved Delivery of Micelles to Tumors Using Sonoporation2.6 Active Targeting with Micelles2.7 Behavior of Micelles at the Cellular Level and Potential Cytotoxicity2.8 Micelles for siRNA Transfection3 Polydiacetylene Micelles Applied to Catalysis3.1 Copper Nanoparticles in Micelles3.2 Copper Salts in Micelles4 Conclusion

Aromatic Amine Catalysts for the O2-Mediated Cross-Dehydrogenative Phenothiazination Reaction?

Metal-free aromatic amines have been utilized recently as redox-active catalysts in various oxidative coupling reactions. In this study, we investigated a series of aromatic amines and their potential redox catalytic activity, in particular compared to our previously reported amino-Te(II) catalysts. The O2-mediated cross-dehydrogenative phenothiazination of phenols was utilized as a benchmark test reaction, as well as the O2-mediated cross-dehydrogenative coupling of indoles. We thus identified a proton sponge as an effective aromatic amine redox catalyst. It was moreover found that although the proton sponge displays clear catalytic activity, it is generally less active than previously reported phenotellurazine catalysts. The insights provided by this study should guide future research efforts for the development of innovative redox-catalyzed cross-dehydrogenative coupling reactions.

Synthesis of a New Heterocyclic System: Pyrimidine Structural Analogues of Natural Integrastatins A, B

In this paper for the first time, we report a simple one-step synthesis of 5-methyl-11,12-dihydro-5H-5,11-epoxybenzo[7,8]oxocino[4,3-d]pyrimidine derivatives by acid-catalyzed cyclization reaction of various 4-methyl-5-acetyl pyrimidine derivatives with salicylic aldehyde. It was shown that 2-substituted 4-methyl-5-acetylpyrimidines successfully react to form a cyclization product. At the same time, 4-methyl-5-acetylpyrimidines with a substituent in the 6th position do not enter into the cyclization reaction. This may be caused by the negative effect of substituents in the 6th position, which hinder the free rotation of the acetyl group and prevent the formation of a stable pre-reaction complex. The structures of the obtained 5-methyl-11,12-dihydro-5H-5,11-epoxybenzo[7,8]oxocino[4,3-d]pyrimidine derivatives were confirmed using 1H NMR and 13C NMR spectroscopy, mass spectrometry, and X-ray diffraction analysis.