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Cyclohepta[b]indoles, prevalent in natural products and pharmaceuticals, are conventionally accessed via metal or Lewis acid‐mediated cycloadditions with prefunctionalized substrates. Our study introduces an innovative sequential catalytic assembly for synthesizing cyclohepta[b]indoles from readily available isatin derivatives. The process involves three catalytic sequences: ring‐closing metathesis, catalytic hydrogenation, and acid‐catalyzed ring expansion. The RCM of 2,2‐dialkene‐3‐oxindoles, formed by butenyl Grignard addition to 3‐allyl‐3‐hydroxy‐2‐oxindoles, yields versatile spirocyclohexene‐3‐oxindole derivatives. These derivatives undergo further transformations, including dibromination, dihydroxylation, epoxidation, Wacker oxidation at the double bond. Hydrogenation of spirocyclohexene‐3‐oxindole yields spirocyclohexane‐3‐oxindoles. Their subsequent acid‐catalyzed ring expansion/aromatization, dependent on the acid catalyst, results in either cyclohepta[b]indoles or cyclohepta[b]indole‐indoline conjugates, adding a unique synthetic dimension. The utility of this methodology is exemplified through the synthesis of an A‐FABP inhibitor, showcasing its potential in pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Derivatives of 2'‐O‐4'‐C‐Ethylene‐bridged Nucleic Acid (ENA) monomer, a nucleoside used in the preparation of antisense modified oligonucleotides and featuring an alkyl group in position 7', are stereoselectively produced in nine steps from commercially available 3‐O‐benzyl‐4‐(hydroxymethyl)‐1,2‐O‐isopropylidene‐alpha‐D‐ribofuranose. The synthesis relies on a sequence of reactions involving a Tebbe olefination, a key ring‐closing metathesis, and an enol ether reduction. [ABSTRACT FROM AUTHOR]

The incorporation of fluorine atoms into an organic compound can alter the chemical reactivity or biological activity of the resulting compound due to the strong electron withdrawing nature of the fluorine atom. We have synthesized many original gem‐difluorinated compounds and described the results in four sections. The first section describes the synthesis of optically active‐gem‐difluorocyclopropanes via the chemo‐enzymatic reaction; we applied these compounds to liquid crystalline molecules, then further discovered a potent DNA cleavage activity for the gem‐difluorocyclopropane derivatives. The second section describes the synthesis of selectively gem‐difluorinated compounds via a radical reaction; we synthesized fluorinated analogues of a sex pheromone of the male African sugarcane borer, Eldana saccharina, and used the compounds as proof for investigating the origin of pheromone molecule recognition on the receptor protein. The third involves the synthesis of 2,2‐difluorinated‐esters by visible light‐driven radical addition of 2,2‐difluoroacetate with alkenes or alkynes in the presence of an organic pigment. The last section describes the synthesis of gem‐difluorinated compounds via the ring‐opening of gem‐difluorocyclopropanes. We further developed a novel method of synthesizing gem‐difluorohomoallylic alcohols via the ring‐opening of gem‐difluorocyclopropane and aerobic oxidation by photo‐irradiation in the presence of an organic pigment. Since gem‐difluorinated compounds that were prepared by the present method have two olefinic moieties with a different reactivity at the terminal position, we accomplished the synthesis of four types of gem‐difluorinated cyclic alkenols via the ring‐closing‐metathesis (RCM) reaction. [ABSTRACT FROM AUTHOR]

Peptides are described as naturally occurring short chains of amino acids and offer great potential as therapeutic agents because of their target selectivity, safe, and well tolerable. Hence, there is an increased interest in peptides in pharmaceutical research and development and approximately more than 170 peptide therapeutics are currently being evaluated in clinical trials and many are being used as therapeutic drugs for various diseases including COVID‐19. The present Review article focuses on recent progress in peptide drug discovery and advancements in synthetic methodologies to enhance their stability and physiological activity of peptides and as well peptidomimetics. [ABSTRACT FROM AUTHOR]

Bicyclic β-lactams constitute an important class of fused-heterocyclic systems which have remained as an effective fighting tool against wide range of bacterial infections throughout 20th century. The importance of these molecules as versatile building blocks has grown exponentially in recent years. In this review, we shall discuss all the latest developments related to syntheses and reactions of bicyclic β-lactams in the last decade. This will provide useful and valuable information for understanding the behavior of bicyclic β-lactams for future development of synthetically/biologically relevant molecules. [Display omitted] [ABSTRACT FROM AUTHOR]

The Lewis superacid bis(perchlorocatecholato)silane catalyzes C−O bond metathesis of alkyl ethers with an efficiency outperforming all earlier reported systems. Chemoselective ring contractions of macrocyclic crown ethers enable substrate‐specific transformations, and an unprecedented ring‐closing metathesis of polyethylene glycols allows polymer‐selective degradation. Quantum chemical computations scrutinize a high Lewis acidity paired with a simultaneous low propensity for polydentate substrate binding as critical for successful catalysis. Based on these mechanistic insights, a second‐generation class of silicon Lewis superacid with enhanced efficacy is identified and demonstrated. [ABSTRACT FROM AUTHOR]

An efficient gold [Au]‐catalyzed one‐pot synthesis has been developed for the construction of biologically interesting mono‐ and bipyridines by utilizing the commercially available cyclic ketones and propargylamine in a sealed tube. The formation of bipyridine derivative 21 a indicates that annulation followed by retro‐Diels–Alder reaction is occurring with norbornene system. However, keto‐derivatives containing bicyclo[2.2.2]octene system 25 indicate that retro‐Diels–Alder reaction is not facile. Compounds 32 a and 33 a were subjected to ring opening cross‐ metathesis to generate diversity and further functionalization of pyridine derivatives. [ABSTRACT FROM AUTHOR]

Asymmetric synthesis of fully functionalized E -cyclodecene core of naturally occurring cyclopropane containing sesquiterpenoid hypocoprins A-C was accomplished. Intramolecular HWE olefination and NHK-coupling reaction failed to provide the desired E -cyclodecene core. Finally, late stage ring closing metathesis (RCM) reaction enables the construction of fully functionalized E -cyclodecene-core of the natural products. Substrate-directed cyclopropanation and Noyori's asymmetric transfer hydrogenation are the key reactions employed to access the RCM precursor. [Display omitted] • Asymmetric synthesis of fully functionalized E -cyclodecene core of naturally occurring cyclopropane containing sesquiterpenoid hypocoprins A-C was accomplished. [ABSTRACT FROM AUTHOR]

Novel spiro chromanone sandwiched 15,16,18 membered (Z)-1,7-dioxo cycloalkenes by Ring Closing Metathesis (RCM) and homodimers of 8-allyl-7-((6-bromo alkyl)oxy) spirochroman-4-ones by Cross Metathesis (CM) were synthesized from simple starting materials 2,4 dihydroxy acetophenone, allyl bromide, and dibromo alkanes. Spiro chromanone is chosen as the core moiety to be incorporated owing to its medicinal and pharmacophoric properties. The concept of molecular hybridization was adopted for the synthesis of compounds 18–26 using Ring Closing Metathesis as a key step. Intermediates 6,7,8 were alkylated with dibromo alkanes to obtain the substrates for RCM and CM, respectively. The dimer dienes 9–17 were made to undergo RCM and the bromo alkyl intermediates 27–34 were made to undergo CM to get homodimers 35–42. [ABSTRACT FROM AUTHOR]

The first total synthesis of the recently isolated natural product thiocladospolide A, along with its C2-epimer, is achieved in nine straightforward linear steps and 12% overall yield. The key feature of the synthesis is the construction of the macrocyclic ring via a late-stage ring-closing metathesis reaction followed by alkene reduction. [ABSTRACT FROM AUTHOR]

Over the last few decades many carbohydrate embedded macrocycles have drawn the attention of synthetic organic chemists because of their interesting chemical and biological properties. Suitably placed chiral 3- and 5-hydroxyl groups of 1,2-O-(1-methylethylidene)-a-D-xylofuranose, derived from inexpensive D-glucose, have been judiciously exploited to generate different non-natural C2-symmetric carbohydrate embedded macrocycles. Different symmetric aromatic and aliphatic hydrophobic spacers have been introduced between highly functionalized cluster of carbohydrate chiral centres through different intra- and intermolecular nucleophilic substitution and ring closing metathesis (RCM) for synthesis of 17 to 24 membered C2-symmetric macrocycles. [ABSTRACT FROM AUTHOR]

An efficient approach for the synthesis of monosubstituted aromatic compounds relying on a ring‐closing metathesis followed by spontaneous 1,2‐elimination is presented. The efficiency for late‐stage functionalization is highlighted in various solvents (up to 920 TON). This approach is compatible with strained cycles and other multiple bonds in the substrate. [ABSTRACT FROM AUTHOR]

An enantioselective synthesis of macrocyclic core of (+)‐callyspongiolide is described, constituting a formal synthesis of this natural product. The synthetic strategy constructs the 14‐membered macrocyclic domain via Yamaguchi esterification followed by a challenging ring‐closing metathesis (RCM) to effect the final formation of the macrolactone. [ABSTRACT FROM AUTHOR]

A short and straight-forward enantioselective synthesis of (R)-(+)-goniothalamin oxide 2 has been achieved with an overall yield of 39% and 99% ee. The synthetic approach involves L-prolinol catalyzed asymmetric epoxidation of cinnamaldehyde followed by Lewis acid-mediated diastereoselective allylation of epoxy aldehyde as the key chiral-inducing steps. [ABSTRACT FROM AUTHOR]

Erythrina alkaloids were identified at the end of the 19th century and today, more than 100 members of the erythrinane family have been isolated. They are characterized by a unique tetracyclic, α-tertiary spiroamine scaffold. Herein we detail our efforts towards the development of a divergent enantioselective synthesis of (+)-dihydro-β-erythroidine (DHβE) – one of the most prominent members of this intriguing family of natural products. 1 Introduction 2 Synthetic Strategy 2.1 First Generation 2.2 Second Generation 2.3 Third Generation 2.3.1 Radical Endgame 2.3.2 Completion of the Total Synthesis 3 Conclusion [ABSTRACT FROM AUTHOR]

The first total synthesis of recently isolated 5(S)-hydroxyrecifeiolide has been described in ten straight forward linear steps with 14% of overall yield. The key reaction involves Jacobsen's hydrolytic kinetic resolution, Copper catalysed Grignard reaction, Steglich esterification and ring closing metathesis reaction using Grubb's 2nd generation catalyst making the synthesis very elegant and simple. The stereogenic center at C5 was generated via Jacobsen's HKR which was confirmed by the Mandelate ester strategy as well as HPLC purity. [ABSTRACT FROM AUTHOR]

A linear synthesis of o‐terphenyl derivatives has been delineated using ring closing metathesis (RCM) as the key step. In this approach, benzil derivatives upon allyl Grignard addition provides diphenyl‐1,2‐diallyl dihydroxy derivatives which undergo ring closing metathesis to afford tetrahydro terphenyl derivatives. Aromatization‐driven dehydration then leads to a diverse set of electron rich and electron deficient o‐terphenyls. Furthermore, oxidative coupling of electron rich o‐terphenyls provides the corresponding triphenylene derivatives. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ring‐closing metathesis (RCM) for the synthesis of macrocycles has been used more and more often over recent years, including some interesting applications on industrial scale. However, like all macrocyclization strategies RCM is plagued by the traditional issue of low volume efficiency. To‐date this is typically addressed in a molecule specific manner with varying degrees of success. Here we report a process intensification method of metathesis macrocyclization that reduces the solvent load required for the reaction significantly. RESULTS: Metathesis macrocylizations were successfully carried out in a solvent volume of upto 82% lower than an equivalent batch reaction, with only minimal impact upon the reaction outcome. A switch of reaction solvent to ethyl acetate renders the process more benign and applicable to large scale. CONCLUSION: A membrane‐assisted processing method that relies upon organic solvent nanofiltration permitting an internal solvent recycling and concumittent in situ product removal. The method is also designed to be applicable to a wide range of metathesis cyclizations. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

ABT-450 (8), a potent hepatitis C (HCV) NS3/4A protease inhibitor, was approved as part of AbbVie's first generation HCV treatment for the United States in December 2014. A series of process optimizations were developed over six years to support the program starting with recycling of a previous protease inhibitor candidate through route development and final process. This discussion will focus on optimization of the final six steps starting from dipeptide 12 and amino acid 13 and highlights the use of a large scale ring closing metathesis (RCM), reactive crystallizations for isolation of intermediates, and detailed process understanding of the final sulfonamide coupling. The process provides ABT-450 (8) in 72% overall yield for the final 6 steps. Image 1 [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • First total synthesis of haploscleridamine. • Elaboration of histidine and use in RCM. • Application of Buchwald-modification of classical Fischer indole synthesis. Abstract Asymmetric total synthesis of the imidazole containing β-carboline natural product, haploscleridamine, from histidine is described. Key to the successful assembly of this alkaloid is a ring-closing metathesis reaction of an imidazole derived allylic alcohol to construct a 3-piperidinone. Application of the Buchwald-modification of the classical Fischer indolization and deprotection of the N -tosyl moiety delivered haploscleridamine. [ABSTRACT FROM AUTHOR]

A convergent and highly stereoselctive synthesis of macrolide framework of aldgamycin – M is described. The salient features of the synthesis are the utilization of enzymatic desymmetrization, Crimmin's non‐Evans syn aldol reaction, Wittig olefination, Yamaguchi esterification and Ring closing metathesis reaction (RCM). A convergent and highly stereoselctive synthesis of macrolide frame work of antibiotic aldgamycin – M is described. The salient features of the synthesis are the utilization of ezymatic desymmetrization, Crimmin's non‐Evans syn aldol, Yamaguchi esterification and RCM. [ABSTRACT FROM AUTHOR]

Abstract Attempts to the construction of B/C ring and E ring in melotenine A are described. Based on para -dienone chemistry, a tactical application of tandem aminolysis/aza-Michael addition reaction was made to access highly functionalized building blocks with the pyrrolo[2,3- d ]carbazole tetracyclic unit (A/B/C/D ring). Albeit negative results for assembling the dihydroazepine unit (E ring) by using the proposed fragmentation reaction of gem -dihalocyclopropanes, an alternative strategy based on ring closing metathesis was evolved to forge the E ring possessing a twisted 1,3-diene unit embedded in the rigid skeleton of melotenine A. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Keywords: gem-Difluorocyclopropane; gem-Difluoromethylene; Radical reaction; Visible light; Ring-opening; Ring closing metathesis EN gem-Difluorocyclopropane; gem-Difluoromethylene Radical reaction Visible light Ring-opening Ring closing metathesis 1 1 1 09/12/23 20230901 NES 230901 The cover picture shows that various types of I gem i -difluorinated molecules have been synthesized I via i the visible light driven reaction, the radical cyclization, and the chemo-enzymatic reaction. Cover Feature: Synthesis of Selectively gem-Difluorinated Molecules; Chiral gem-Difluorocyclopropanes via Chemo-Enzymatic Reaction and gem-Difluorinated Compounds via Radical Reaction (Chem. Rec. 9/2023) Gem-Difluorocyclopropane; gem-Difluoromethylene, Radical reaction, Visible light, Ring-opening, Ring closing metathesis. [Extracted from the article]

Herein we report on a 96-well plate assay based on the fluorescence resulting from the ring-closing metathesis of two profluorophoric substrates. To demonstrate the validity of the approach, four commercially available ruthenium-metathesis catalysts were evaluated in six different solvents. The results from the fluorescent assay agree well with HPLC conversions, validating the usefulness of the approach.

Two ruthenium olefin metathesis initiators featuring electronically modified quinoline-based chelating carbene ligands are introduced. Their reactivity in RCM and ROMP reactions was tested and the results were compared to those obtained with the parent unsubstituted compound. The studied complexes are very stable at high temperatures up to 140 °C. The placement of an electron-withdrawing functionality translates into an enhanced activity in RCM. While electronically modified precatalysts, which exist predominantly in the trans-dichloro configuration, gave mostly the RCM and a minor amount of the cycloisomerization product, the unmodified congener, which preferentially exists as its cis-dichloro isomer, shows a switched reactivity. The position of the equilibrium between the cis- and the trans-dichloro species was found to be the crucial factor governing the reactivity of the complexes.

Abstract: Total synthesis of (–)–6–epi–hygrophorones B14 and (–)–4–epi–hygrophorone D14 was achieved using stereoselective Grignard reaction, Bernet–Vasella protocol and Ring closing metathesis, starting from D–mannose. [ABSTRACT FROM AUTHOR]

Abstract: Total synthesis of (–)–6–epi–hygrophorones B14 and (–)–4–epi–hygrophorone D14 was achieved using stereoselective Grignard reaction, Bernet–Vasella protocol and Ring closing metathesis, starting from D–mannose. [ABSTRACT FROM AUTHOR]

Total synthesis of THP tethered pyrone containing natural product cryptopyranmoscatone B2 was accomplished from commercially available 2-deoxyribose. The key THP unit was assembled by FeCl 3 catalyzed cyclization of an allyl alcohol. Brown allylation and RCM reactions were employed to construct the lactone unit. The synthesis represents the first total synthesis of the putative structure of the natural product. [ABSTRACT FROM AUTHOR]

(‐)‐Nakadomarin A is an alkaloid belongs to manzamine family having architecturally complex structure and exhibits promising biological activities. To accomplish this target molecule, few novel synthetic strategies have been developed by eminent synthetic chemists. This review will highlight the important and improved synthetic approaches for the total synthesis of natural as well as unnatural isomers of nakadomarin A. All synthetic strategies have been enlightened from the cluster of literatures to develop a more elegant strategy for the molecule in future. [ABSTRACT FROM AUTHOR]

A simple and efficient total synthesis of patulolide A from readily available 7-octen-1-ol is reported by asymmetric synthetic approach. The key reactions involved are asymmetric dihydroxylation using AD-mix-βand Grubbs’ ring-closing metathesis reaction for the synthesis macrocyclic ring system. [ABSTRACT FROM AUTHOR]

The expeditious route for the synthesis of γ-butyrolactone fused cyclooctene starting from the γ-butyrolactone fused cyclopentane through bicyclo[4.2.1]nonan-9-one is reported. Retro-Dieckmann's condensation of bicyclo[4.2.1]nonan-9-one in presence of sodium methoxide and methanol furnished γ-butyrolactone fused cyclooctene in good yield. Surprisingly, the stereochemistry of ringjunction of γ-butyrolactone fused cyclooctene is different from the γ-butyrolactone fused cyclopentane, and the position of new ester group, which were confirmed unambiguously by X-ray analysis. [ABSTRACT FROM AUTHOR]

A short approach to chiral diaza-olefines from protected 2,2′-diamino-1,1′-binaphthyl is presented. Cis- and trans-olefines can be selectively obtained by twofold N-allylation followed by RCM or by bridging a 2,2′-diamino-1,1′-binaphthyl precursor with trans-1,4-dibromo-2-butene. Deprotection afforded cis- and trans-dihydro[1,6]diazecines 1 in 58 and 64% overall yield. The reactivity of the but-2-ene-1,4-diyl fragment was investigated yielding corresponding epoxides, diols, and mono- and dibromo products. In several cases rearrangements and participation of the proximate N-Boc group was observed. In no case could allylic substitution be accomplished. From 13 compounds X-ray structure analyses could be obtained.

A modified method is reported for the conversion of unsaturated sulfonamides into their cyclic saturated counterparts. This method utilises a single palladium catalyst for an intramolecular Heck reaction and subsequent transfer hydrogenation, which is achieved in one-pot following the addition of ammonium formate. Accordingly, a range of fourteen structural variations are reported and under optimal conditions the adducts were generated in typically good to excellent yields. Notably, discrimination of differentially substituted dienes can be accomplished in the case of compounds 28 and 29 and the process was only observed to fail with the more sterically hindered precursor 32 . [ABSTRACT FROM AUTHOR]