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The Minisci reaction constitutes a straightforward and convenient strategy to achieve the direct C–H functionalization of heterocyclic molecules. This radical-based reaction platform has received increasing attention due to the predictability of its outcome according to the nature of the radicals and heterocycles involved. Considering the importance of these heterocyclic scaffolds in the development and production of drug molecules, it is inevitable that scaling up this reaction manifold is of utmost importance. This review will present recent strategies to achieve the goal, which mostly involve implementing the reaction conditions under continuous flow. [ABSTRACT FROM AUTHOR]

Heterocycles are important compounds existed in diverse advanced chemicals, functional materials, bioactive molecules and natural products. Different strategies through transition metal‐catalyzed alkyne cyclization have been developed to synthesize various heterocycles. The merger of alkyne cyclization and metal nanoparticle catalysis has emerged as an important approach to diverse heterocycles. By using different kinds of metal nanoparticle catalysts, such as gold, silver, copper and palladium nanoparticles, a number of heterocycles are prepared with high yield and selectivity in a green, sustainable and highly efficient manner. This review summarizes and discusses recent achievements in metal nanoparticle‐catalyzed alkyne cyclization for the synthesis of heterocycles. [ABSTRACT FROM AUTHOR]

Camptothecin and its analogues show important antitumor activity and have been used in clinical studies. However, hydrolysis of lactone in the E ring seriously attenuates the antitumor activity. To change this situation, aromathecin alkaloids are investigated in order to replace camptothecins. Potential antitumor activity has obtained more and more attention from organic and pharmaceutical chemists. As a member of the aromathecin alkaloids, rosettacin has been synthesized via different methods. This review summarizes recent advances in the synthesis of rosettacin. [ABSTRACT FROM AUTHOR]

Peptidomimetics have been extensively explored in many area due to their ability to improve pharmacological qualities and interesting biological activities. Cycles could be incorporated in peptides to reduce their flexibility, often enhancing the affinity for a certain receptor. Many efforts have been made to synthesize various peptidomimetics. Among them, the Ugi reaction is a popular way for the synthesis of peptidomimetics because it provides peptide‐like products. The Ugi reaction consists of the condensation of an aldehyde or ketone, a carboxylic acid, an amine, and an isocyanide usually giving a linear peptidomimetic. In order to obtain other linear, cyclic or polycyclic peptidomimetics, the acyclic products have to undergo additional transformations or cyclizations. This review covers the years from 2018–2023, regarding the synthesis of linear, cyclic and polycyclic peptidomimetics, employing Ugi reactions eventually followed by post‐Ugi transformations. Organo‐catalyzed reactions, base‐promoted reactions, and metal‐free reactions toward peptidomimetics are highlighted. [ABSTRACT FROM AUTHOR]

In the realm of flow chemistry, Do-It-Yourself (DIY) flow setups represent a versatile and cost-effective alternative to expensive commercially available reactors. Not only they are budget friendly, but also unlock a world of possibilities for researchers to explore and create customized setups tailored to their specific needs. This minireview serves as a short compendium of DIY flow systems to assist flow researchers in the challenging task of finding a suitable setup for their experiments and facilitate the transition from batch to flow chemistry. Our goal is to demonstrate that flow chemistry can be affordable, easy-to-build, and reproducible at the same time. Therefore, herein we review and describe selected illustrative examples of easily assembled/constructed DIY flow setups, with a particular emphasis on how to select the most suitable one based on the specific chemistry of interest, ranging from simple homogeneous monophasic reactions to more complex systems for photo-, electrochemistry, and so on. In addition, we briefly comment on the significance of DIY approach on education, particularly its integration into the standard undergraduate curriculum as a key educational tool for young chemists. Ultimately, we hope this mini review will help and encourage the reader to go with the flow and get started with the fine art of flow chemistry. [ABSTRACT FROM AUTHOR]

(1) Background Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. (2) Methods This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants escitalopram and sertraline or antipsychotics risperidone and aripiprazole according to the latest state-of-the-art international dosing recommendations for CYP2C19 and CYP2D6 metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. (3) Conclusions This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines. [ABSTRACT FROM AUTHOR]

Under microwave (MW) irradiation at 150 °C in toluene and in the presence of nucleophiles (DMAP, triphenylphosphine and tetrahydrothiophene) 1‐substituted 1‐ethynyl‐2‐vinyldi‐ and tetrahydroisoquinolines undergo [3,3]‐sigmatropic rearrangement providing pyrrolo[2,1‐b][3]benzazepines in good yields. The replacement of toluene with acetonitrile directs the rearrangement towards the formation of 7,11b‐dihydro‐6H‐pyrido[2,1‐a]isoquinolines. [ABSTRACT FROM AUTHOR]

The use of visible light and photoredox catalysis emerged as a powerful and sustainable tool for organic synthesis, showing high value for distinctly different ways of bond creation. Halogenated compounds are the cornerstone of contemporary organic synthesis: it is almost impossible to develop a route towards a pharmaceutical reagent, agrochemical, natural product, etc. without the involvement of halogen-containing intermediates. Moreover, the halogenated derivatives as final products became indispensable for drug discovery and materials science. The idea of this review is to understand and summarise the impact of visible light-promoted chemistry on halogenation and halofunctionalisation reactions. [ABSTRACT FROM AUTHOR]

The highly efficient construction of complicated heterocyclic frameworks in an atom‐ and step‐economic manner is still one of the cores of synthetic chemistry. Dearomatization reactions show the unique advantage for the construction of functionalized heterocycles and have attracted widespread attention over the past two decades. The metal‐free approach has proved to be a green and sustainable paradigm for the synthesis of spirocyclic, polycyclic and heterocyclic scaffolds, which are widely present in natural products and bioactive molecules. In this review, the advances in the recent six years (2017–2023) in metal‐free dearomatization reactions are highlighted. Emphasis is placed on developments in the field of organo‐catalyzed dearomatization reactions, oxidative dearomatization reactions, Brønsted acid‐ or base‐promoted dearomatization reactions, photoredox‐catalyzed dearomatization reactions, and electrochemical oxidation dearomatization reactions. [ABSTRACT FROM AUTHOR]

The Ugi reaction has become one of the highly explored reactions for the formation of multifunctional adducts, due to the mild reaction conditions, wide scope and high variability. By carefully selecting the starting four components, Ugi‐adducts could undergo different kinds of post‐transformations for the synthesis of bioactive heterocycles, natural products and macrocycles. Considering the significance of polycycles, diverse post‐Ugi transformations have been developed over the years for constructing structurally novel polycycles. In this account, we summarize important efforts for the synthesis of polycyclic N‐heterocycles via post‐Ugi cyclizations from the Van der Eycken laboratory onwards 2016. With the aid of transition metal catalysis from gold, rhodium, silver and palladium, as well as metal‐free strategies, versatile polyheterocycles are prepared with high efficiency and step‐economy. [ABSTRACT FROM AUTHOR]

This paper provides a review on various methodologies developed for the synthesis of different indolizine derivatives and an overview of their application. These include thienoindolizine and indolizino[8,7‐b]indole derivatives. The indolizine nucleus occurs as privileged scaffold of many natural and synthetic molecules with significant biological activity. Fused‐indolizines such as thienoindolizines and indolizinoindole derivatives are of great interest, due to their antitumor, antimicrobial and enzyme inhibitor activity. Because of their widespread use in chemical, medicinal, biological, and materials science research, indolizines and their fused derivatives are attractive synthetic targets in the search for efficient methods for their construction. [ABSTRACT FROM AUTHOR]

A novel method of transition metal‐free N−S bond cleavage and subsequent C−N bond activation of Ugi‐adducts was developed. Diverse primary amides and α‐ketoamides were prepared in a rapid, step‐economical and highly efficient manner in two steps. This strategy features excellent chemoselectivity, high yield and functional‐group tolerance. Primary amides derived from the pharmaceuticals probenecid and febuxostat were prepared. This method opens a new pathway for the simultaneous synthesis of primary amides and α‐ketoamides in an environmentally friendly manner. [ABSTRACT FROM AUTHOR]

Copper-catalyzed enantioselective coupling has been widely investigated, which allows rapid construction of various chiral molecules. Despite important advances via polar and radical mechanisms, exploring general and practical strategies for the regio-, enantio- and diastereoselective assembly of stereogenic centers is of significant value but remains highly problematic. The integration of photocatalysis with asymmetric copper catalysis could provide appealing access to the development of new reaction pathways and structurally diverse chiral compounds, and extend the boundaries of radical chemistry. This review summarizes recent advances in photoinduced copper-catalyzed enantioselective coupling reactions, and discusses the mechanistic aspects. [ABSTRACT FROM AUTHOR]

The isoindolo[2,1‐b]isoquinolin‐5(7H)‐one scaffold is widely present in lots of bioactive natural products. Diverse types of strategies have been developed to construct this scaffold. Recently, transition metal‐catalyzed C−H activation/annulation is emerging as a powerful and straightforward method to construct diverse polyheterocycles with high atom‐ and step‐economy. It also has been employed for the synthesis of the isoindolo[2,1‐b]isoquinolin‐5(7H)‐one scaffold. This review provides an introduction to recent advances for the preparation of isoindolo[2,1‐b]isoquinolin‐5(7H)‐ones by using transition metal‐catalyzed C−H activation/annulation. It will help researchers to find hidden opportunities and accelerate the discovery of novel transformations based on C−H activation/annulation. [ABSTRACT FROM AUTHOR]

1,3‐Dipolar cycloadditions are the preferred method to generate five‐membered heterocyclic rings. Surprisingly, cycloadditions based on acyl‐isocyanide ylides have remained underexplored by the chemical community. Acyl‐isocyanide ylides readily react with dipolarophiles, such as substituted alkenes, to yield Δ1‐pyrroline derivatives. As an explanation for the observed reactivity of this reaction is lacking, extensive density functional theory calculations were performed to scrutinize the mechanistic features of the transformation. Herein we explain the experimental outcome of the reaction using a variety of reactivity theories and predict opposed regioselectivity for electron‐poor and electron‐rich dipolarophiles. With the insights obtained, we hope to incentivize the design of new cycloaddition reactions based on the acyl‐isocyanide ylides motif. [ABSTRACT FROM AUTHOR]