Recent advances in the oxidative activation of the C2-C3 π bond of indoles and its applications.

The oxidative C2-C3 π bond activation strategy is the most efficient tool to synthesize oxygen-containing indoline, which frequently appears in natural products with various biological activities as structural units. Recently, the oxidation-induced cascade strategy through oxygenation activation of the indolic C2-C3 π bond of indoles has received much attention for its use in efficiently establishing complex indoline with oxygen-containing molecular architectures, and holds tremendous potential in the total synthesis of indole alkaloids. It can be carried out using potential activated indole radical cations or imine cation intermediates produced oxidative C2-C3 π bond activation of indole with various nucleophiles or ring-forming reagents by employing simple and non-decorated indoles as starting substrates.

Maltodextrin vitamin E succinate: A novel antioxidant emulsifier for formulating functional nanoemulsions.

A new multifunctional emulsifier was synthesized by coupling maltodextrin with a dextrose equivalent of 19 to vitamin E succinate. Two emulsifiers with varying degrees of vitamin E succinate substitution were prepared based on different mass ratios of vitamin E succinate to maltodextrin. The molecular structure and purity of these emulsifiers were analyzed.

Mechanochemical deprotection of -butoxycarbonyl (Boc) group using basic alumina.

A solvent-free, operationally simple, and chemoselective mechanochemical method for -butoxycarbonyl (Boc) deprotection is described. In a planetary ball mill, -Boc groups from protected heterocycles, amides, and anilines, as well as -Boc groups from carbonates, can be removed selectively, using basic alumina. This high-yielding protocol avoids tedious extraction and column chromatography.

Recent advances in oxidative dearomatization involving C-H bonds for constructing value-added oxindoles.

Exploring three-dimensional chemical space is an important research objective of organic synthetic chemistry. Oxidative dearomatization (ODA) is one of the most important and powerful tools for realizing this goal, because it changes and removes aromatic structures from aromatic compounds to increase levels of saturation and stereoisomerism by direct addition reactions between functional groups with aromatic cores under oxidative conditions. As a hot topic in indole chemistry, the synthetic value of the oxidative dearomatization of indoles has been well recognized and has witnessed rapid development recently, since it could provide convenient and unprecedented access to fabricate high-value-added three-dimensional oxindole skeletons, such as C-quaternary indolones, polycycloindolones and spiroindolones, and be widely applied to the total synthesis of these oxindole alkaloids.

Diastereoselective Access to Triazolo[1,2-]indolines via a Bio-Inspired Oxidative Cyclization of NH-Indoles.

Establishing three-dimensional chemicals by using the C-C π bond of indoles has always been a research hotspot in organic synthesis; however, employing the oxidative C-C π bond of indoles to generate imine which would lead to the N-C π bond cyclization under metal-free conditions is still rare. Here, we report a bio-inspired synthesis of triazolo[1,2-]indolines by the oxidative cyclization between -indoles and azomethine imines with 3,3-dimethyldioxirane as the sole oxidant under metal-free and mild conditions. This finding represents an elegant instance of tri-functionalization of -indoles, which provides rapid access to a broad range of triazolo[1,2-]indolines with tetrahydroisoquinolines in one single step.

Assembly of 5-dibenzo[,]cycloheptenes by a formal [5 + 2] annulation of -aryl alkynyl benzyl alcohols with arenes.

A new synthetic methodology for the synthesis of 5-dibenzo[,]cycloheptenes from -aryl alkynyl benzyl alcohols and arenes a TfO-mediated formal [5 + 2] annulation reaction has been achieved. From this transformation, structurally diverse 5-dibenzo[,]cycloheptenes were achieved in moderate to good yields. This transformation probably involves an intermolecular Friedel-Crafts-type alkylation and a subsequent intramolecular 7- cyclization in one pot, highlighting the high efficiency, regioselectivity, and step-economy of this protocol.

The synthesis of furoquinolinedione and isoxazoloquinolinedione derivatives as selective Tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.

Based on our previous study on the development of the furoquinolinedione and isoxazoloquinolinedione TDP2 inhibitors, the further structure-activity relationship (SAR) was studied in this work. A series of furoquinolinedione and isoxazoloquinolinedione derivatives were synthesized and tested for enzyme inhibitions. Enzyme-based assays indicated that isoxazoloquinolinedione derivatives selectively showed high TDP2 inhibitory activity at sub-micromolar range, as well as furoquinolinedione derivatives at low micromolar range.

Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation.

Inhibitors and nucleic acid based techniques were two main approaches to interfere with protein signaling and respective cascade in the past. Until recently, a new class of small molecules named proteolysis-targeting chimeras (PROTACs) have emerged. Each contains a target warhead, a linker and an E3 ligand.

CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors.

Cyclin-dependent kinases 8 (CDK8) regulates transcriptional process via associating with the mediator complex or phosphorylating transcription factors (TF). Overexpression of CDK8 has been observed in various cancers. It mediates aberrant activation of Wnt/β-catenin signaling pathway, which is initially recognized and best studied in colorectal cancer (CRC).

Synthesis, cytotoxicity and structure-activity relationship of indolizinoquinolinedione derivatives as DNA topoisomerase IB catalytic inhibitors.

Our previous studies reveal that indolizinoquinolinedione scaffold is a base to develop novel DNA topoisomerase IB (TOP1) catalytic inhibitors. In this work, twenty-three novel indolizinoquinolinedione derivatives were synthesized. TOP1-mediated relaxation, nicking and unwinding assays revealed that three fluorinated derivatives 26, 28 and 29, and one N,N-trans derivative 46 act as TOP1 catalytic inhibitors with higher TOP1 inhibition (++++) than camptothecin (+++) and without TOP1-mediated unwinding effect.

Synthesis and structure-activity relationship of furoquinolinediones as inhibitors of Tyrosyl-DNA phosphodiesterase 2 (TDP2).

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a recently discovered enzyme specifically repairing topoisomerase II (TOP2)-mediated DNA damage. It has been shown that inhibition of TDP2 synergize with TOP2 inhibitors. Herein, we report the discovery of the furoquinolinedione chemotype as a suitable skeleton for the development of selective TDP2 inhibitors.

Highly diastereoselective oxa-[3+3] cyclization with C,N-cyclic azomethine imines via the copper-catalyzed aerobic oxygenated C[double bond, length as m-dash]C bond of indoles.

Herein, a copper-catalyzed highly diastereoselective aerobic oxygenated [3+3] cyclization of 3-substituted indoles with C,N-cyclic azomethine imines using oxygen as the sole oxidant under mild conditions has been developed. This protocol provides a simple and convenient approach for constructing [2,3]-fused indoline O-heterocycles bearing two pharmaceutically intriguing parts, tetrahydroisoquinoline and indoline. Good yields and excellent diastereoselectivity under mild reaction conditions were observed.

Syntheses and antibacterial activity of soluble 9-bromo substituted indolizinoquinoline-5,12-dione derivatives.

In our previous research, 9-bromo indolizinoquinoline-5,12-dione 1 has been found to be a good anti-MRSA agent. However, it had very low bioavailability in vivo possibly due to its low solubility in water. In order to obtain the derivatives with higher anti-MRSA activity and good water solubility, twenty eight bromo-substituted indolizinoquinoline-5,12-dione derivatives were synthesized in the present study.

Synthesis and biological evaluation of 6-substituted indolizinoquinolinediones as catalytic DNA topoisomerase I inhibitors.

In our previous work, indolizinoquinolinedione derivative 1 was identified as a Top1 catalytic inhibitor. Herein, a series of 6-substituted indolizinoquinolinedione derivatives were synthesized through modification of the parent compound 1. Top1 cleavage and relaxation assays indicate that none of these novel compounds act as classical Top1 poison, and that the compounds with alkylamino terminus at C-6 side chain, including 8, 11-16, 18-21, 25, 26 and 28-30, are the most potent Top1 catalytic inhibitors.