Beilstein Journal of Organic Chemistry最新文献

Organic five-membered rings have shown significant applications in the fields of organic synthesis, natural products, organic materials and pharmaceuticals for their unique characteristics. Electrochemical construction of five-membered rings from alkynes attracted increasing attention due to the notable advantages of electrochemical transformations and facile access of alkynes. Indole skeletons were constructed successfully through electrochemical intramolecular coupling of ethynyl-involved ureas, annulation of o-arylalkynylanilines, cyclization of 2-ethynylanilines, selenocyclization of diselenides with 2-ethynylanilines as well as C-H indolization of 2-alkynylanilines with 3-functionalized indoles. Isoindolones were synthesized successfully by electrochemical annulation of benzamides with terminal alkynes, 5-exo-dig aza-cyclization of 2-alkynylbenzamides as well as reductive cascade annulation of o-alkynylbenzamides. Pyrroles and imidazoles were formed efficiently via electrochemical annulation of alkynes with enamides and tandem Michael addition/azidation/cyclization of alkynes, amines and azides, respectively. Imidazopyridines could be obtained by electrochemical [3 + 2] cyclization of heteroarylamines. The electrochemical oxidative [3 + 2] cycloaddition of secondary propargyl alcohols was a simple and efficient access towards 1,2,3-triazoles. In this review, electrochemical cyclizations of alkynes to construct five-membered rings are highlighted. Firstly, the property and application of five-membered rings are simply introduced. After presenting the usefulness of alkynes and the general progress of electrochemical transformations, electrochemical cyclization reactions of alkynes towards five-membered rings are classified and presented in detail. Based on different types of five-membered rings, electrochemical construction of indoles, isoindolinones, indolizines, oxazoles, imidazoles, pyrroles, imidazoles and 1,2,3-triazoles are summarized and the possible reaction mechanisms are disclosed if available.

The carbonyl group is central in organic synthesis, thanks to its ability to undergo a vast range of different chemical transformations on its carbon center or at the neighboring positions. Due to the high level of oxygen content in biomass, small molecules arising from biomass often possess a carbonyl group. This is why biobased platform molecules possessing a carbonyl group, either under the form of an aldehyde, a ketone, an acid or an ester, play a dominant role in biobased chemistry. This review aims at illustrating how the chemistry of biobased carbonyl platform molecules with backbones from C₂ to C₆ offers opportunities to reach all kinds of chemical architectures, sometimes even complex ones benefiting from the ability of the carbonyl group to be involved in multicomponent reactions.

The desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds is a powerful tool for the construction of ring systems bearing multiple stereocenters including all-carbon quaternary stereocenters, which are widely useful chiral building blocks for the total synthesis of structurally complex natural products. On the other hand, terpenoids and alkaloids, with their intricate and diverse skeletal frameworks as well as the broad range of biological activities, have long been a major focus for synthetic chemists. Over the past fifteen years, significant progress has been made in the total synthesis of complex terpenoid and alkaloid natural products by strategically applying desymmetric enantioselective reduction. Advance before 2016 in this area has been overviewed in an elegant review article. Since then, a series of more challenging terpenoid and alkaloid natural products have been synthesized utilizing a desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds as a key transformation. This review will summarize the application of this strategy in the total synthesis of terpenoid and alkaloid natural products from the year 2016 to 2025. We first focus on the synthesis of several terpenoids and alkaloids through the desymmetric enantioselective reduction of five-membered cyclic 1,3-dicarbonyl compounds. Subsequently, the utilization of six-membered cyclic 1,3-dicarbonyl compounds for the synthesis of some terpenoids natural products is described.

We report herein the fourth generation of our synthetic strategy to chaetominine-type alkaloids featuring two modifications of the last step of our 4 to 6-step approach. Firstly, by employing EDCI/HOBt as the coupling system for the last step of the one-pot O-debenzylation-lactamization reaction, the overall yield of our previous total synthesis of (-)-isochaetominine A was increased from 25.4% to 30.8% over five steps. Secondly, a new protocol featuring the use of an aged solution of K₂CO₃/MeOH to quench the DMDO epoxidation-triggered cascade reaction was developed, which allowed the in situ selective mono- or double epimerization at C11/C14 as shown by the diastereodivergent synthesis of a pair of diastereomers of versiquinazoline H from its tripeptide precursor. This double epimerization at the last-step allowed the enantiodivergent synthesis of two enantiomers in either racemate form or two pure enantiomers from the same precursor. The former was demonstrated by the synthesis of alkaloid 14-epi-isochaetominine C that was used to determine the enantiomeric excess of the synthesized natural product (98.7% ee), while the latter was illustrated by the synthesis of both enantiomers of the alkaloid isochaetominine. Additionally, the reported structures of alkaloids aspera chaetominines A and B have been synthesized. Moreover, the four-step synthesis of the reported structure of aspera chaetominine B generated another diastereomer that was converted in one-pot to (-)-isochaetominine C, which turned out to be the revised structure of aspera chaetominine B.

Indolo[1,2-c]quinazoline derivatives have emerged as promising chemotype in drug discovery due to their versatile biological activities, including antimicrobial and antiviral properties. In this study, we report the design, synthesis, and biological evaluation of novel indolo[1,2-c]quinazoline derivatives, with a particular focus on their antiproliferative potential against human cancer cells. We introduced structural modifications at positions 5, 6, and 12 of the indolo[1,2-c]quinazoline core to explore the structure-activity relationships and enhance cytotoxicity. Our results highlight that 12-aminomethyl derivatives exhibited notable cytotoxicity against tumor cell lines, with the highest activity observed for compound 9c, which showed significant selectivity toward tumor cells. In contrast, while the compounds demonstrated planar polycyclic structures, DNA was not the primary target for their antiproliferative effects, as confirmed by FID assay and fluorescence titration studies. This study represents the first comprehensive evaluation of indolo[1,2-c]quinazolines as potential scaffold for the development of antitumor agents, offering valuable insights into their SAR and paving the way for a future evaluation of these compounds as anticancer therapeutics.

Bioinspired total synthesis represents an important concept to guide the designing of powerful synthetic strategies. Our group has a long-time interest and experience in designing synthetic strategies through analyzing the biosynthetic pathway of natural products. Recently, we have achieved an array of bioinspired total syntheses, which showed the great power of this approach in natural product synthesis. Documented herein is a review of these achievements which include the detailed process of how we develop these strategies. Specifically, bioinspired total synthesis of three types of natural products, namely diterpenoids (chabranol, and monocerin), alkaloids (indole, hydroquinoline, and monoterpenoid-indolidinoid hybrid), and gymnothelignans are discussed. Based on these achievements on bioinspired total synthesis, we provide some information on how to use this important strategy in natural product synthesis.

Azobenzene-based solar thermal fuels have undergone significant advancements over the past four decades, emerging as a promising technology for light-to-thermal energy conversion. While these materials exhibit considerable development potential, critical challenges remain that hinder their practical implementation. In this perspective, we systematically analyze four representative azobenzene-based solar thermal fuel systems including nanocarbon-hybrid, conjugated polymer, linear polymer, and small-molecule derivative formulations to trace their developmental trajectories and identify key limitations. Through this comparative analysis, we aim to clarify the current state of azobenzene-based solar thermal fuels, while mapping strategic pathways for future technological advancements in this rapidly evolving research field.

Switchable multicomponent reactions involving 3-substituted-5-amino-1,2,4-triazoles, pyruvic acid, and salicylaldehydes were studied under different conditions. Upon conventional heating, benzotriazolooxadiazocine-5-carboxylic acids were formed in the three-component reactions as single reaction products. Upon ultrasonic activation or mechanical stirring at room temperature, the multicomponent reaction of the same starting materials led to the formation of only tetrahydrotriazolopyrimidine derivatives.

A small library of bis- and tetraamides was synthesized by the Ugi reaction with α-ketoglutaric acid, tert-butyl isocyanide, aromatic aldehydes, and aromatic amines. When o-azidoanilines were used, azidated peptidomimetics were obtained, the post-cyclization of which by the aza-Wittig reaction yielded a series of substituted 3-(3-oxo-3,4-dihydroquinoxalin-2-yl)propanoic acids containing a pharmacophore quinoxalinone moiety. The tandem Ugi/aza-Wittig combination was also carried out in a one-pot procedure without isolation of the intermediate.