Search

Comprehensive Summary Salimabromide, a unique and scarce marine tetracyclic polyketide, was synthesized in both racemic and optically active forms. A novel carboxylic acid‐directed method for tandem oxidative difunctionalization of olefins was developed, whereby the formation of bridged butyrolactone and enone moieties occurs concurrently. Density functional theory (DFT) calculations indicate that this reaction follows a [3+2] process rather than the [2+2] process. In the meantime, the distinctive benzo‐fused [4.3.1] carbon skeleton and highly hindered vicinal quaternary stereocenters were simultaneously constructed through a challenging intramolecular Giese‐Baran radical cyclization. Furthermore, deuterium kinetic isotopic effects were utilized to enhance the efficacy of this pivotal step. This represents a new illustration of the application of kinetic isotope effects in natural product synthesis. Then, the short asymmetric synthesis of (+)‐salimabromide (13 or 15 steps) was accomplished by combing this method with rhodium‐catalyzed enantioselective hydrogenation of a cycloheptenone derivative (97% ee) or conjugate addition of an aryl boronic acid with 2‐cyclohepten‐1‐one (> 99% ee). [ABSTRACT FROM AUTHOR]

The iboga alkaloids are a family of monoterpene indole alkaloids first discovered from the root of Tabernanthe iboga. The major alkaloid constituent in the root, ibogaine, has garnered interest for its anti‐addictive properties. Ibogaine has been shown to reduce opiate, amphetamine, alcohol, and nicotine self‐administration in rodents. However, ibogaine itself is less than optimal as a treatment in humans for Substance Abuse Disorder (SUD) due to its cardiotoxicity and hallucinogenic potential. Instead, ibogaine is an attractive lead for drug discovery efforts. Indeed, several notable programs have been launched to both elucidate ibogaine's mechanism of action and reduce its toxicity. While there have been over 20 total syntheses of ibogamine, ibogaine, and closely related family members, there are far fewer syntheses of recently isolated iboga alkaloids. In this targeted review, we discuss the synthetic strategies applied to the synthesis of classical and non‐classical iboga alkaloids. [ABSTRACT FROM AUTHOR]

AbstractAn efficient and concise synthesis of phomopsolidone B was accomplished in nine longest linear steps from readily available chiral template, L-arabinose and L-ethyl lactate. The synthesis features rapid access to the key chiral backbone from chiral pools and the formation of furanone skeleton employing a late-stage olefin cross-metathesis. [ABSTRACT FROM AUTHOR]

On the basis of a novel ynol‐diene cyclization developed as a rapid access to tropone unit, the first divergent strategy to 17‐nor‐cephalotane diterpenoids has been successfully established. Combining with a bioinspired stereoselective dual hydrogenation, the divergent total synthesis of (+)‐3‐deoxyfortalpinoid F, (+)‐harringtonolide, (−)‐fortalpinoids M/N/P, and analog (−)‐20‐deoxocephinoid P have been achieved in 14–17 linear longest steps starting from commercially available materials. [ABSTRACT FROM AUTHOR]

This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer–Villiger oxidation of cyclohexanone, which was developed to produce seven‐membered lactones and establish the required stereochemistry at the C14 position (92 % yield, 99 % ee, 500 mg scale). Cis‐ and trans‐tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid‐triggered, tunable acyl‐Pictet–Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl‐Pictet–Spengler cyclization cascade. By strategically using these two reactions and the late‐stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids. [ABSTRACT FROM AUTHOR]

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5‐dimethoxy‐tetrahydrofuran employing an organocatalytic domino‐aldol reaction, a Mizoroki‐Heck reaction, a Wittig reaction as well as an oxidation‐decarboxylation sequence. The (15R)‐epimer significantly reduced GABA‐induced currents through GABAA receptors while its (15S)‐epimer did not show any significant effect. These data suggest that (15R)‐PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators. [ABSTRACT FROM AUTHOR]

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5‐dimethoxy‐tetrahydrofuran employing an organocatalytic domino‐aldol reaction, a Mizoroki‐Heck reaction, a Wittig reaction as well as an oxidation‐decarboxylation sequence. The (15R)‐epimer significantly reduced GABA‐induced currents through GABAA receptors while its (15S)‐epimer did not show any significant effect. These data suggest that (15R)‐PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators. [ABSTRACT FROM AUTHOR]

ABSTRACT A concise and efficient synthesis of the γ‐lactam‐fused azaphenanthrene alkaloid eupolauramine has been achieved. The key feature of the synthesis involves Au(I)‐catalyzed cycloisomerization of N‐naphthyl aminobutynamide intermediate and subsequent intramolecular Ullmann‐type coupling reaction. This study clearly demonstrated the usefulness of coinage metal‐catalyzed cycloisomerization strategy in the construction of architecturally sophisticated pyridine‐fused heterocyclic scaffolds. [ABSTRACT FROM AUTHOR]

This review outlines the synthesis of alkyl citrate natural products using cyclobutene diester precursors. The approach is efficient and stereoselective and provides the correct oxidation state of the citrate core of these compounds. The synthesis of a number of alkyl citrates along with some higher oxidised members of this family is detailed. This review outlines the synthesis of alkyl citrate natural products using cyclobutene diester precursors. This highly stereoselective approach gives the citrate core with the correct oxidation state and allows for the synthesis of a large selection of these interesting natural products. Furthermore, stepwise oxidation provides access to the higher oxidised alkyl citrates from a common intermediate. (Image credit: Nikolai Rossouw.) [ABSTRACT FROM AUTHOR]

A novel and concise synthetic method for arenastatin A, a cytotoxic cyclic depsipeptide of marine origin, was developed in this study. The convergent assembly of the four segments, including the cross-metathesis reaction, gave a cyclization precursor, and Fmoc deprotection caused simultaneous macrocyclization. The Corey–Chaykovsky reaction using a chiral sulfur ylide afforded arenastatin A with complete stereoselectivity in the longest linear sequence of seven reaction steps from the known compound. Using this synthetic method, some analogs of segment B were prepared through a late-stage diversification strategy. The simple SN2 reaction of the thiolate toward the tosylate precursor, prepared using almost the same synthetic method as described above, provided the desired sulfide analogs. [ABSTRACT FROM AUTHOR]

Salvinorin A is a powerful hallucinogen in humans, and a selective, high efficacy agonist of the kappa‐opioid receptor (κ‐OR). Salvinorin A is the first plant‐derived ligand with high selectivity for κ‐OR over other receptors, its structure is unrelated to any known opioid receptor ligands, even lacking any nitrogenous moieties. Mechanistically and pharmacologically, salvinorin A is distinct from other known hallucinogens in humans, making it the only selective κ‐OR ligand to gain wide‐spread interest outside of research. Structurally, salvinorin A bares a highly functionalized trans‐decalin core, containing two quaternary centers, and is fused to a δ‐lactone baring a furan moiety. Synthetic access of salvinorin A has been elusive due to a highly sensitive epimerizable center at carbon 8 (C8). All these features make salvinorin A a highly challenging synthetic target. With multiple synthetic efforts from around the world, only nine completed syntheses have been achieved to date. This review is intended to provide a look at the key strategies used to achieve the syntheses reported to date. We will summarize the efforts towards the syntheses of salvinorin A starting from Evans in 2007 to Barriault in 2023. [ABSTRACT FROM AUTHOR]

Various strategies for synthesis and stereroselective aldol coupling of furan‐3(2H)‐ones were evaluated that eventually enabled a highly stereroselective synthesis of the C8‐C22 fragment of tuscoron A. [ABSTRACT FROM AUTHOR]

A highly effective enantioselective monobenzoylation of 1,3‐diols has been developed for the synthesis of 1,1‐disubstituted tetrahydro‐β‐carbolines. The chemistry has been successfully applied to the asymmetric total synthesis of (+)‐alstrostine G, which also features a cascade Heck/hemiamination reaction enabling facile construction of the pivotal pentacyclic core. [ABSTRACT FROM AUTHOR]

A Pro‐Gly‐typed cyclopeptide, cyclosenegalin A, was firstly isolated from Annona senegalensis and Annona scleroderma. In this study, we reported synthesis the cycloheptapeptide with a combination of solid‐ and solution‐phase synthetic methods. This study also compared the effectiveness of β‐turn inducer type I and II in cyclosenegalin A to facilitate the cyclization process. The synthesis of cyclosenegalin A were prepared using two different sequences of linear peptides for cyclization. First sequence employed β‐turn type I inducer (Ser‐Ala‐Val‐Thr) as turning point and second sequence employed β‐turn type II inducer (Thr‐Pro‐Gly‐Leu). The successful cyclization was obtained using the linear sequence of NH2‐Ala‐Val‐Thr‐Pro‐Gly‐Leu‐Ser‐OH with β‐turn type II. The final product was obtained in 8.2 % yield with PyBOP/DIEA act as coupling agent. The synthetic cyclosenegalin A were characterized with HR‐ToFMS, 1H NMR, 13C NMR, HSQC, HMBC, TOCSY, and ROESY. The synthetic product was also evaluated for its antimicrobial activity. [ABSTRACT FROM AUTHOR]

Comprehensive Summary The first total synthesis of neopetromin, featuring the highly strained Tyr C‐6‐to‐Trp N‐1’ linkage, is hereby reported. This modular synthetic strategy, employing C—H arylation and Larock macrocyclization, offers a novel approach to the synthesis of various RiPPs natural product families. [ABSTRACT FROM AUTHOR]

Licorice (Glycyrrhiza uralensis Fisch), a significant traditional Chinese herbal medicine, has been extensively utilized in China to treat various ailments. Natural bioactive coumarins, glycycoumarin, glycyrin, and 3-O-methylglycyrol, were isolated from licorice, and they exhibited various pharmacological properties. In this report, we have accomplished the total synthesis of glycycoumarin, glycyrin, and 3-O-methylglycyrol in 5–7 linear steps from commercially available 2,4,6-trihydroxybenzaldehyde with yields of 12.3–21.2%. Additionally, their anti-inflammatory activities were studied and compared. Glycycoumarin, glycyrin, and 3-O-methylglycyrol exhibited different levels of anti-inflammatory activities, with glycyrin being the most potent. Mechanistic studies indicated that glycyrin exerted its anti-inflammatory properties by inhibiting the activation of TNF-α, IL-6, and IL-1β, making it a potential anti-inflammatory lead compound for further optimization and discovery of new agents. [ABSTRACT FROM AUTHOR]

We describe the first total syntheses of tabernanthine and ibogaline. Entry to these iboga alkaloid natural products is enabled by a thermal coupling of indoles and aziridines to furnish the requisite nosyl tryptamine starting materials. This route features a Friedel‐Crafts type alkylation to form the key indole‐isoquinuclidine C−C bond. Finally, a regio‐ and diastereoselective hydroboration‐oxidation enables C−N bond formation to close the isoquinuclidine ring system and deliver tabernanthine and ibogaline in 10 and 14 % yield respectively. Both syntheses were completed in eight steps. [ABSTRACT FROM AUTHOR]

We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A. These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Pseudolaric acids are a family of diterpenoid natural products that exhibit a broad spectrum of biological activities. The main structural feature of their framework is a trans‐fused perhydroazulene bearing a bridged lactone positioned at the junction of the rings. Herein, we have developed a radical cyclization strategy that allows flexible tuning of the cyclization process through diverse silicon substitutions on the substrates. This strategy can assist in constructing a series of skeletons with structural resemblance to pseudolaric acids and expedites the construction of the bridged lactone. Finally, it facilitates the synthesis of the entire skeletal structure of the pseudolaric acid family of natural products, excluding the B‐ring functionalization. [ABSTRACT FROM AUTHOR]

In this Account, we summarize the development of a new strategy for streamlined synthesis of tetrahydropyran-embedded macrolactones and its successful implementation to a 13-step synthesis of (–)-exiguolide and an 11-step synthesis of (+)-neopeltolide. 1 Introduction 2 Development of Macrocyclization/Transannular Pyran Cyclization Strategy 3 Total Synthesis of (–)-Exiguolide 4 Total Synthesis of (+)-Neopeltolide 5 Conclusions [ABSTRACT FROM AUTHOR]

Ecklonialactones, Eiseniachlorides, and Egregiachlorides are synthesized in living organisms via the lipoxygenase‐mediated oxidation of polyunsaturated fatty acids. Originally isolated and identified from brown seaweed (Ecklonia stolonifera, Eisenia bicyclis, and Egregia menziesii), and later replicated on milligram scale through chemical synthesis, the full biological activities of these compounds remain to be elucidated. To bridge this gap in knowledge, we propose a unified methodology to synthesize the 14‐membered macrocyclic structures of Ecklonialactones, Eiseniachlorides and analogs using a versatile and convergent approach. This study delineates the synthesis of Ecklonialactone A, B, C, D, and Eiseniachlorides A and B, as well as ent‐Ecklonialactone B, 16‐epi‐Ecklonialactone B and 12,13‐diepi‐Ecklonialactone B. [ABSTRACT FROM AUTHOR]

Herein, we report a concise and efficient formal synthesis of (+)-hannokinol. Key to this new strategy is the use of a chiral Horner–Wittig reagent, readily available from 2-deoxy-D-ribose, to introduce the chiral 1,3-diol motif. [ABSTRACT FROM AUTHOR]

In this overview, naturally occurring resorcylic lactones biosynthetically derived from alternariol and almost exclusively produced by fungi, are discussed with view on their isolation, structure, biological activities, biosynthesis, and total syntheses. This class of compounds consists until now of 127 naturally occurring compounds, with very divers structural motifs. Although only a handful of these toxins (i.e., alternariol and its 9-O-methyl ether, altenusin, dehydroaltenusin, altertenuol, and altenuene) were frequently found and isolated as fungal contaminants in food and feed and have been investigated in significant detail, further metabolites, which were much more rarely found as natural products, similarly show interesting biological activities.

Tropane alkaloids are an important class of biologically active small molecules characterized by their 8-azabicyclo[3.2.1]octane core. Because of their numerous medicinal applications, microbial biosynthesis and a variety of chemical syntheses have been designed for individual family members. However, current approaches are not amenable to late-stage structural diversification at N8, C3, C6, or C7, positions that are critical for modulating the biological properties of these molecules. Here, we describe a general approach to the synthesis of tropane alkaloids and their analogues that relies on the construction of the 8-azabicyclo[3.2.1]octane core through aziridination of a cycloheptadiene intermediate, followed by vinyl aziridine rearrangement. Using this strategy, we synthesized six tropane alkaloids and several analogues in only 5-7 steps. Given that the tropane alkaloid scopolamine has been reported to promote structural neuroplasticity and produce antidepressant effects, we tested five tropane-containing compounds for their ability to promote dendritic spine growth in cultured cortical neurons. We found that the orientation of the C3 substituent may play a role in the psychoplastogenic effects of tropane alkaloids. Our work provides a robust platform for producing tropane analogs for future structure-activity relationship studies.

A steadily increasing number of reports have been published on chemo-enzymatic synthesis methods that integrate biosynthetic enzymatic transformations with chemical conversions. This review focuses on the total synthesis of natural products and classifies the enzymatic reactions into three categories. The total synthesis of five natural products: cotylenol, trichodimerol, chalcomoracin, tylactone, and saframycin A, as well as their analogs, is outlined with an emphasis on comparing these chemo-enzymatic syntheses with the corresponding natural biosynthetic pathways.

Abstract Cyclobutanes are distributed widely in a large class of natural products featuring diverse pharmaceutical activities and intricate structural frameworks. The [2 + 2] cycloaddition is unequivocally the primary and most commonly used method for synthesizing cyclobutanes. In this review, we have summarized the application of the [2 + 2] cycloaddition with different reaction mechanisms in the chemical synthesis of selected cyclobutane-containing natural products over the past decade. Graphical Abstract

Aberrant changes in the gut microbiota are implicated in many diseases, including inflammatory bowel disease (IBD). Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity, indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD. Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies, novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed. Herein, we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone (an enantiomer) as a potent agent against experimental colitis that acts by modulating the gut microbiota. 5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids (SCFAs); thus, it regulates the intestinal immune system by reducing proinflammatory immune cell numbers, and maintains intestinal mucosal integrity by modulating tight junctions (TJs). Moreover, 5S-heudelotinone (2) ameliorates colitis-associated colorectal cancer (CAC) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced in situ carcinoma model. Together, these findings reveal the potential of a novel natural product, namely, 5S-heudelotinone, to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.

This account summarizes the author's endeavors in target-oriented synthesis at Seoul National University since 2011. A collection of the most celebrated molecules in total synthesis are revisited and the author's solutions to these historical challenges are presented. In particular, the unique perception of their molecular frameworks and unprecedented bond-forming sequences form the basis of the newly developed strategies. Together with a 'personal touch' on these selected stories, the author hopes that this account will offer new insights and fresh perspectives for all levels of enthusiasts of target-oriented total synthesis. 1 Introduction 2.1 Synthesis of Strychnine 2.2 Synthesis of Actinophyllic Acid 2.3 Synthesis of Dendrobine 2.4 Synthesis of Communesin 2.5 Synthesis of Morphinans 2.6 Synthesis of Reserpine 2.7 Synthesis of Quinine and Quinidine 2.8 Synthesis of Haouamine 2.9 Future Work 3 Summary and Outlook 4 Abbreviations [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Treponema is a Gram‐negative anaerobic bacterium, among which the pathogenic Treponema can cause various diseases, such as venereal syphilis (Treponema pallidum), yaws (Treponema carateum), and oral diseases (Treponema denticola and Treponema medium). Although different from conventional lipopolysaccharides, the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine development. Hence, we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L‐ornithine (L‐Orn) and D‐aspartic acid (D‐Asp) derivatives. The efficiency of non‐reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and acceptors. Our [3+1] glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group, thereby improving the efficiency of synthesizing the target tetrasaccharide. The L‐Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency. Therefore, the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional‐group modifications have provided valuable insights for synthesizing other complex bacterial glycans. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Collective syntheses of A. baumannii CPS K43, K47 and K88 repeating units have been accomplished via a new α‐glycosylation method with GlcN3 as donors, which features: 1) mild reaction conditions, 2) good to high yields, 3) excellent stereoselectivities. The synthetic route also highlights an orthogonal one‐pot coupling strategy on the basis of glycosyl ortho‐(1‐phenylvinyl)benzoates for stereoselective constructions of both 1,2‐trans and 1,2‐cis glycosidic bonds, precluding the issues of aglycone transfer. [ABSTRACT FROM AUTHOR]

Acremolactone B is a pyridine‐containing azaphilone‐type polyketide. The first total synthesis of this molecule was achieved on a gram scale, based on an aza‐6π electrocyclization–aromatization strategy for construction of the tetra‐substituted pyridine ring. A bicyclic intermediate was expeditiously prepared by using [2+2] photocycloaddition and chemoselective Baeyer–Villiger oxidation, which was further elaborated to a densely substituted aza‐triene. An electrocyclization–aromatization cascade was utilized to forge the tetracyclic core of this natural product, and the side chain was introduced through diastereoselective acylation and reduction. [ABSTRACT FROM AUTHOR]

The cluster of four skipped exo‐methylene substituents on the "northern" wing of limaol renders this dinoflagellate‐derived marine natural product unique in structural terms. This arguably non‐thermodynamic array gains kinetic stability by virtue of populating local conformations which impede isomerization to a partly or fully conjugated polyene. This analysis suggested that the difficulties encountered during the late stages of our first total synthesis of this polyketide had not been caused by an overly fragile character of this unusual substructure; rather, an unfavorable steric microenvironment about the spirotricyclic core was identified as the likely cause. To remedy the issue, the protecting groups on this central fragment were changed; in effect, this amendment allowed all strategic and practical problems to be addressed. As a result, the overall yield over the longest linear sequence was multiplied by a factor of almost five and the material throughput increased more than eighty‐fold per run. Key‐to‐success was a gold‐catalyzed spirocyclization reaction; the reasons why a Brønsted acid cocatalyst is needed and the origin of the excellent levels of selectivity were delineated. The change of the protecting groups also allowed for much improved fragment coupling processes; most notably, the sequence of a substrate‐controlled carbonyl addition reaction followed by Mitsunobu inversion that had originally been necessary to affix the southern tail to the core could be replaced by a reagent controlled asymmetric allylation. Finally, a much‐improved route to the "northern" sector was established by leveraging the power of asymmetric hydrogenation of a 2‐pyrone derivative. Limaol was found to combine appreciable antiparasitic activity with very modest cytotoxicity. [ABSTRACT FROM AUTHOR]

The given text is a scientific research article that provides detailed information about the synthesis and characterization of various chemical compounds. It includes measurements, physical properties, spectroscopic data, and reaction conditions for the compounds synthesized. The article is technical and specific to the field of chemistry, and may be useful for researchers studying organic chemistry and chemical synthesis. [Extracted from the article]

Comprehensive Summary: Collective syntheses of A. baumannii CPS K43, K47 and K88 repeating units have been accomplished via a new α‐glycosylation method with GlcN3 as donors, which features: 1) mild reaction conditions, 2) good to high yields, 3) excellent stereoselectivities. The synthetic route also highlights an orthogonal one‐pot coupling strategy on the basis of glycosyl ortho‐(1‐phenylvinyl)benzoates for stereoselective constructions of both 1,2‐trans and 1,2‐cis glycosidic bonds, precluding the issues of aglycone transfer. [ABSTRACT FROM AUTHOR]

The Daphniphyllum alkaloids represent a particularly diverse class of complex diterpene alkaloids, which are characterized by their enormous structural diversity. The daphnicyclidins, a subgroup of these alkaloids, stand out due to their unique pentafulvene structural motif. This review article gives an overview of the compounds that have been isolated so far and can be assigned to this subgroup. Furthermore, all synthesis approaches and total syntheses published to date are presented. [ABSTRACT FROM AUTHOR]

Angucyclines and angucyclinones represent a class of natural compounds that belong to the group of aromatic polyketides. They exhibit a wide array of biological properties, such as antimicrobial, antiviral, and cytotoxic. Their considerable therapeutic potential and diverse scaffolds have attracted many synthetic chemists to devise novel strategies to construct their intricate molecular architecture. Over 300 class members have been isolated from natural sources, mainly from bacterial strains of Streptomyces species. This review highlights recent advancements in their synthesis, such as oxidative cyclization, photooxidation, and metal‐catalyzed [4+2]‐cycloaddition, which has facilitated the efficient and practical total syntheses of various angucycline and angucyclinone natural products. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The first total synthesis of talaroconvolutin A (1.1 g obtained) and talarofuranone has been achieved using accessible materials (12 steps, 7.5% and 8.2% yields, respectively). Convergent routes involved intramolecular Diels−Alder reactions in two approaches for creating the decalin moiety. Additionally, an unprecedented DMP‐mediated domino reaction resulted in the deoxy‐tetramic acid system. These syntheses not only establish the absolute configuration of talaroconvolutin A but also enable further collaborative studies of this type of ferroptosis inducers. [ABSTRACT FROM AUTHOR]

This article discusses a study on a new method for a visible-light-induced three-component radical coupling. The researchers tested the reaction of selenocarbonates and selenocarbamates and found that increasing the stability of the acyl radical facilitated the reaction. They also explored the reaction under thermal and photochemical conditions and provided detailed experimental data. The research has potential applications in natural-products synthesis and provides insights into the mechanism of the reaction and its potential applications in organic synthesis. [Extracted from the article]

This article discusses the synthesis of 7a-substituted pyrrolizidine derivatives through stereocontrolled anionic cyclization. The derivatives have potential therapeutic applications and the authors describe a new route for their synthesis using proline derivatives and epichlorohydrin. The compounds were successfully synthesized with controlled stereochemistry and characterized using spectroscopic techniques. The text provides detailed information on the reactions, yields, physical properties, and spectroscopic data of the compounds, making it a valuable resource for researchers studying organic chemistry and chemical synthesis. [Extracted from the article]

The total synthesis of two new marine natural products, (±)-marinoaziridine B 7 and (±)-N-methyl marinoaziridine A 8, was accomplished. The (±)-marinoaziridine 7 was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy were the preparation of the chiral epoxide (±)-5 using the Johnson Corey Chaykovsky reaction, followed by the ring-opening reaction and the Staudinger reaction. The N,N-dimethylation of compound (±)-7 gives (±)-N-methyl marinoaziridine A 8. The NMR spectra of synthetized (±)-marinoaziridine B 7 and isolated natural product did not match. The compounds are biologically characterized using relevant in silico, in vitro and in vivo methods. In silico ADMET and bioactivity profiling predicted toxic and neuromodulatory effects. In vitro screening by MTT assay on three cell lines (MCF-7, H-460, HEK293T) showed that both compounds exhibited moderate to strong antiproliferative and cytotoxic effects. Antimicrobial tests on bacterial cultures of Escherichia coli and Staphylococcus aureus demonstrated the dose-dependent inhibition of the growth of both bacteria. In vivo toxicological tests were performed on zebrafish Danio rerio and showed a significant reduction of zebrafish mortality due to N-methylation in (±)-8. [ABSTRACT FROM AUTHOR]

In our continuing search for biologically active new chemical entities from marine organisms, we have isolated a new cyclic depsipeptide, PM170453 (1), from a cyanobacterium of the genus Lyngbya sp., collected in the Indo-Pacific Ocean. Structure elucidation of the isolated compound was determined by spectroscopic methods including MS, 1H, 13C and 2D-NMR. To solve the supply problem for 1 and progress pharmaceutical development, the total synthesis of 1 that involves a total of 20 chemical steps in a convergent process was carried out. Its in vitro cytotoxic activity against four human tumor cell lines, as well as the inhibition of the interaction between the programmed cell death protein 1 PD-1 and its ligand PD-L1 were also evaluated. [ABSTRACT FROM AUTHOR]

A de novo asymmetric strategy for the synthesis of d‐bradyrhizose diastereomers from an achiral ketoenolester precursor is described. Key transformations used in the stereodivergent approach include two Noyori asymmetric reductions, an Achmatowicz rearrangement, diastereoselective alkene oxidations, and the first example of a palladium(0)‐catalyzed glycosylation of a vinylogous pyranone. The isomeric composition of the bicyclic reducing sugars obtained was analyzed and their behaviour was compared to the natural product, revealing key stereocentres that impact the overall distribution. [ABSTRACT FROM AUTHOR]

Herein, we describe a simple and efficient pathway for the total synthesis of pyranicin and 4‐epi‐pyranicin by utilizing carbohydrates as chiral raw materials for the first time. The general synthetic strategy involves the formation of two main fragments: Fragment 1 is the central tetrahydropyran core, which was constructed in a total of 10 steps from 2,3,4,6‐tetra‐O‐acetyl D‐glucal via Ferrier‐type rearrangement and oxidative cyclization as the key steps. Fragment 2 is the butenolide fragment, which was obtained in a gram scale with a total of 14 steps from diacetyl‐L‐rhamnal involving a ring contraction strategy. [ABSTRACT FROM AUTHOR]

A unified approach to access the naturally occurring cyclic tetrapeptide JM‐47 and some of its structural variants from a common macrocyclic scaffold has been developed. The key reactions involved a difficult macrocyclization to access the scaffold, and its late‐stage diversification by cross‐metathesis to access the natural product as well as analogues. The synthesis proceeded in good overall yield and high stereochemical integrity. It also confirms the structure and configuration assigned to JM‐47. [ABSTRACT FROM AUTHOR]

A de novo asymmetric strategy for the synthesis of d‐bradyrhizose diastereomers from an achiral ketoenolester precursor is described. Key transformations used in the stereodivergent approach include two Noyori asymmetric reductions, an Achmatowicz rearrangement, diastereoselective alkene oxidations, and the first example of a palladium(0)‐catalyzed glycosylation of a vinylogous pyranone. The isomeric composition of the bicyclic reducing sugars obtained was analyzed and their behaviour was compared to the natural product, revealing key stereocentres that impact the overall distribution. [ABSTRACT FROM AUTHOR]

Cyclobutanes are distributed widely in a large class of natural products featuring diverse pharmaceutical activities and intricate structural frameworks. The [2 + 2] cycloaddition is unequivocally the primary and most commonly used method for synthesizing cyclobutanes. In this review, we have summarized the application of the [2 + 2] cycloaddition with different reaction mechanisms in the chemical synthesis of selected cyclobutane-containing natural products over the past decade. [ABSTRACT FROM AUTHOR]

The cosmopolitan marine Roseobacter clade is of global biogeochemical importance. Members of this clade produce sulfur‐containing amino lipids (SALs) involved in biofilm formation and marine surface colonization processes. Despite their physiological relevance and abundance, SALs have only been explored through genomic mining approaches and lipidomic studies based on mass spectrometry, which left the relative and absolute structures of SALs unresolved, hindering progress in biochemical and functional investigations. Herein, we report the structural revision of a new group of SALs, which we named cysteinolides, using a combination of analytical techniques, isolation and degradation experiments and total synthetic efforts. Contrary to the previously proposed homotaurine‐based structures, cysteinolides are composed of an N,O‐acylated cysteinolic acid‐containing head group carrying various different (α‐hydroxy)carboxylic acids. We also performed the first validated targeted‐network based analysis, which allowed us to map the distribution and structural diversity of cysteinolides across bacterial lineages. Beyond offering structural insight, our research provides SAL standards and validated analytical data. This information holds significance for forthcoming investigations into bacterial sulfonolipid metabolism and biogeochemical nutrient cycling within marine environments. [ABSTRACT FROM AUTHOR]

This document describes a concise total synthesis of (±)-stepharine and (±)-pronuciferine, two bioactive natural products. The synthesis involves several key steps, including a Catellani reaction and an Au-catalyzed cyclization, to assemble the 1-methylene-THIQ scaffold. An oxidative dearomatization reaction is then used to construct the spiro-cyclohexadienone scaffold. The overall yield of (±)-stepharine is 21% and (±)-pronuciferine is 19%. The NMR spectra of the synthesized compounds are consistent with those previously reported. The document provides a detailed account of the chemical synthesis process and the techniques used to purify and characterize the compounds. [Extracted from the article]

Comprehensive Summary: As one of the most common structural motifs in natural products, cyclopentenones usually can be fabricated by Nazarov cyclization using divinyl ketones or functionalized tertiary divinyl carbinols (TDCs) as substrates. However, straightforward method for transforming unfunctionalized TDCs to their corresponding cyclopentenones is currently lacking. Herein, we wish to report the total syntheses of four structurally distinct terpenoids, namely laurane‐type marine sesquiterpenoids isolaurene, debromoaplysin and aplysin, and guaiane sesquiterpenoid guaiadienone A, all using a novel synthetic method, named oxidative Nazarov cyclization, as the key step. This work demonstrated our robust method is suitable for synthesizing various highly substituted cyclopentenones. [ABSTRACT FROM AUTHOR]

Ent‐kaurane diterpenes are a large group of natural products, with more than 1,000 compounds since their discovery. Due to their excellent biological activities and complex polycyclic structures, these compounds have attracted organic synthesis chemists around the world to be devoted to achieve their total synthesis. At present, the isolated C‐20‐oxygenated ent‐kaurane diterpenes are the most abundant of these natural products, reaching more than 350 in number. However, only total syntheses of 3,20‐epoxy, 7,20‐epoxy and 19,20‐lactone ent‐kaurane diterpenes have been reported. In this review, we elaborate the synthesis of these three types of C‐20 oxygenated ent‐kaurane natural products, discuss these synthetic strategies in detail, and provide good guidance and reference for the synthesis of other C‐20 oxygenated compounds. [ABSTRACT FROM AUTHOR]