Mapping of Some Further Alkylation-Initiated Pathways to Polyheterocyclic Compounds from Indigo and Indirubin.

The reaction of indigo with two equivalents of the electrophile ethyl bromoacetate with caesium carbonate as a base result in the formation of structurally complex polyheterocyclics, including a fused spiroimidazole and a spiro[1,3]oxazino derivative, together with a biindigoid-type derivative, through a convenient one-pot reaction. Further assessment of the reaction using five equivalents of the electrophile gave rise to other molecules incorporating the 2-(7,13,14-trioxo-6,7,13,14-tetrahydropyrazino[1,2-:4,3-']diindol-6-yl) scaffold. The reaction of ethyl bromoacetate with the less reactive indirubin resulted in the synthesis of three derivatives of a new class of polyheterocyclic system via a cascade process, although yields were low.

Palladium-Catalyzed (3+2) and (4+2) Cycloaddition Reactions of Sulfamidate Imine-Derived Azadienes: Synthesis of Spirocyclic Pyrrolidines and Tetrahydroquinolines.

Diastereoselective Pd-catalyzed (3+2) and (4+2) cycloaddition reactions of sulfamidate imine-derived 1-azadienes with zwitterionic N-dipoles derived from 1-tosyl-2-vinylaziridine and 4-vinylbenzoxazinone have been developed. These reactions provide highly functionalized azaspirocycles featuring three contiguous stereocenters. The sulfonyl imine moiety of the cycloadducts can be fully reduced to access valuable β-amino alcohols.

Current and Ongoing Developments in Targeting Infection and Recurrence.

is a Gram-positive, spore-forming anaerobic bacterial pathogen that causes severe gastrointestinal infection in humans. This review provides background information on infection and the pathogenesis and toxigenicity of . The risk factors, causes, and the problem of recurrence of disease and current therapeutic treatments are also discussed.

Design, Synthesis, and Evaluation of Cephamycin-Based Antisporulation Agents targeting .

With the aim of discovering small molecule inhibitors of the sporulation process in , we prepared a series of C-7 α-(4-substituted-1-1,2,3-triazol-1-yl)acetamide analogues of cefotetan, a known inhibitor of the sporulation-specific protein target SpoVD. These analogues were evaluated using both binding assays with SpoVD and antisporulation assays against . Further design concepts were aided utilizing the predicted docking scores (DS) using both AlphaFold (AF) models, and a crystal structure of the SpoVD protein (PDB 7RCZ).

Synthesis of 7α-Methoxy-7-(4-phenyl-1-1,2,3-triazol-1-yl)acetamino-3'-arylthio-cephalosporic Acid Derivatives from 7-Aminocephalosporic Acid.

The aim of this project was to develop a synthetic protocol for the preparation of a cephamycin scaffold that would readily allow the synthesis of its analogues with variations at the C-7 amino group and the C-3' position. We also aimed to develop a method that avoided the use of toxic and potentially explosive diphenyldiazomethane. These aims were achieved via the synthesis of the novel α-bromo acetamide which allowed functionalization at the α-bromo acetamide position by azide and then the introduction of a 4-phenyl-1-1,2,3-triazol-1-yl moiety via a Cu(I)-catalysed azide-alkyne cycloaddition reaction with phenylacetylene.

Diastereoselective Pd-catalyzed Decarboxylative (4+2) Cycloaddition Reactions of 4-Vinylbenzoxazinanones and 2-Nitro-1,3-enynes.

A formal palladium-catalyzed decarboxylative (4+2) cycloaddition reaction between 4-vinylbenzoxazinanones and 2-nitro-1,3-enynes has been developed to produce highly valuable, densely functionalized tetrahydroquinolines in moderate to excellent yields with high diastereoselectivity under mild reaction conditions. The optimised protocol tolerates a range of substituted 2-nitro-1,3-enynes, which represent an under-utilized class of dipolarophile for transition-metal catalyzed cycloadditions. The employed reaction methodology facilitates efficient cycloaddition with both N-H- and N-Ts-4-vinylbenzoxazinanone dipole precursors.

DFT Mechanistic Insights into the Ni(II)-Catalyzed Enantioselective Arylative Cyclization of Tethered Allene-Ketones.

Density functional theory (DFT) has provided a detailed mechanistic picture for the redox neutral nickel(II)-catalyzed arylative cyclization reactions of a tethered allene-ketone with arylboronic acids. A mechanistic rationale for the high diastereo- and enantioselectivity achieved experimentally at high reaction temperature was uncovered through modeling the reaction with a chiral ligand and the predicted stereochemical outcome corroborates with experimental results. An unprecedented mechanism for the base-free organoboron transmetalation was revealed and the regioselectivity of migratory insertion of tethered allene-ketones as well as the stability of the possible allylnickel isomers (σ-allyl vs π-allyl) were clarified.

Diastereoselective Petasis-Borono-Mannich Crotylation Reactions of Chiral α-Heteroatom (F, OBz, OH) Aldehydes: Rapid Access to Valuable Mono and Bicyclic Heterocyclic Scaffolds.

The crotylation reactions of chiral α-F, α-OBz and α-OH aldehydes under Petasis-borono-Mannich conditions using (E)- or (Z)-crotylboronates and primary amines resulted in γ-addition products in high dr and high er. α-F and α-OBz aldehydes gave 1,2-anti-2,3-syn and 1,2-anti-2,3-anti, products, respectively while an α-OH aldehyde gave 1,2-syn-2,3-syn products. The stereochemical outcomes of reactions of the former aldehydes can be explained using a six-membered ring transition state (TS) model in which a Cornforth-like conformation around the imine intermediate is favoured resulting in 1,2-anti products.

Palladium-catalysed enantio- and regioselective (3 + 2) cycloaddition reactions of sulfamidate imine-derived 1-azadienes towards spirocyclic cyclopentanes.

An enantio- and diastereoselective Pd-catalysed (3 + 2) cycloaddition of bis(trifluoroethyl) 2-vinyl-cyclopropane-1,1-dicarboxylate (VCP) with cyclic sulfamidate imine-derived 1-azadienes (SDAs) has been developed. These reactions provide highly functionalized spiroheterocycles having three contiguous stereocentres, including a tetrasubstituted carbon bearing an oxygen functionality. The two geminal trifluoroethyl ester moieties can be manipulated in a facially selective manner to afford more diversely decorated spirocycles with four contiguous stereocentres.

Synthesis of the Purported Structure of Glyphaeaside C and Proposed Revisions to the Structures of the Glyphaeaside Alkaloids.

The 10 glyphaeaside alkaloids isolated from the roots of were originally purported as piperidine-based 1--alkylated iminosugars, with the A-, B-, and C-type glyphaeasides bearing l-DFJ, DGJ, and DNJ ring configurations, respectively. Subsequent investigations have revealed glyphaeaside C as being a pyrrolidine-based iminosugar with a DMDP ring configuration via total synthesis of the revised structure. In this work, side chain diastereomers of the originally purported structure of glyphaeaside C () and two related α-1--alkylated DNJ derivatives were synthesized from a common precursor, which was prepared in turn via stereoselective Grignard addition to a protected d-glycosylamine, followed by a reductive amination-cyclization sequence.

Nickel Phosphite-Catalyzed Tetradehydro-Diels-Alder Reactions of ()-3-ene-1,8-diynes.

A nickel-catalyzed tetradehydro-Diels-Alder reaction of ()-3-ene-1,8-diynes for the preparation of isoindolines, dihydroisobenzofurans, and tetrahydroisoquinolines has been developed. A series of air-stable nickel catalysts were used in this study, including the novel nickel(0)-phosphite catalysts, Ni[P(O-3,5-Me-Ph)], Ni[P(O-1-naphthyl)], and Ni[P(O-2-naphthyl)]. To help understand the type of intermediate in the initial cycloisomerization process, the trapping of nickellacycle intermediates with pinacolborane to yield vinyl boronates is also discussed.

The Roots of (A. Rich) Verdcourt: Further Evidence of Its Antidiarrhoeal Activity.

Despite the current management options and therapeutics used in the treatment of diarrhoea, in Africa and Asia, diarrhoea remains a major concern, especially in children under the age of 5 years. Traditional knowledge of medicinal plants used in the management of diarrhoea symptoms can be explored for their efficacy. In Nigeria, the TMPs (Traditional Medicine Practitioners) have, over the years, employed medicinal plants in the management of diarrhoea symptoms.

Anti-inflammatory properties of novel galloyl glucosides isolated from the Australian tropical plant Uromyrtus metrosideros.

Two new galloyl glucosides, galloyl-lawsoniaside A (4) and uromyrtoside (6), were isolated from the polar fraction of Uromyrtus metrosideros leaf extract along with another four previously identified phytochemicals (1, 2, 3, and 5). The structures of these six compounds were characterised using low and high-resolution mass spectrometry (L/HRMS) and 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy. These compounds were not toxic to human peripheral blood mononuclear cells (PBMCs) at 10 μg/mL over 24 h, yet showed significant in vitro suppression of proinflammatory cytokines involved in the pathogenesis of inflammatory bowel disease (IBD).

Synthesis of - and enantioenriched -β-amino alcohols by highly diastereoselective borono-Mannich allylation reactions.

A highly diastereoselective method for the synthesis of -β-amino alcohols and enantioenriched -β-amino alcohols has been developed involving α-hydroxyl aldehydes and chiral α-phenylaminoxyaldehydes or α-benzoyloxyaldehydes, respectively in Petasis borono-Mannich allylation reactions. This study broadens the scope and utility of the Petasis reaction to include pinacol allylboronate and highlights its unique reactivity and stereochemical outcomes.

A Rare Alder-ene Cycloisomerization of 1,6-Allenynes.

Thermally induced cycloisomerization reactions of 1,6-allenynes gives α-methylene-γ-lactams via intramolecular Alder-ene reactions. The mechanism is supported by computational and deuterium labelling studies. This thermal, non-radical method enables the discovery of a hitherto unknown route that proceeds via a divergent mechanism distinct from the previous [2+2] cycloisomerization manifold.

The Pd-catalysed asymmetric allylic alkylation reactions of sulfamidate imines.

The Pd-catalysed asymmetric allylic alkylation (Pd-AAA) of prochiral enamide anions derived from 5-oxathiazole 2,2-dioxides has been developed. Various 4,5-disubstituted and 4-substituted cyclic sulfamidate imines have participated in the transformation with a range of allyl carbonates-as well as 2-vinyl oxirane, 2-vinyl--tosylaziridine, and 2-vinyl-1,1-cyclopropane dicarboxylate-to furnish the desired -allylated products in moderate to high yields, with high regioselectivites and generally high enantioselectivities. Conversion between - and -allyl products was observed, with the -allylated products converting to the -allylated products over time.

Isolation of bioactive compounds from medicinal plants used in traditional medicine: Rautandiol B, a potential lead compound against Plasmodium falciparum.

Background: Neorautanenia mitis, Hydnora abyssinica, and Senna surattensis are medicinal plants with a variety of traditional uses. In this study, we sought to isolate the bioactive compounds responsible for some of these activities, and to uncover their other potential medicinal properties.

Methods: The DCM and ethanol extracts of the roots of N.

Cationic Peptidomimetic Amphiphiles Having a -Aryl- or -Naphthyl-1,2,3-Triazole Core Structure Targeting () : Synthesis, Antibacterial Evaluation, and an In Vivo Infection Model.

(also known as ) is a Gram-positive anaerobic, spore producing bacterial pathogen that causes severe gastrointestinal infection in humans. The current chemotherapeutic options are inadequate, expensive, and limited, and thus inexpensive drug treatments for infection (CDI) with improved efficacy and specificity are urgently needed. To improve the solubility of our cationic amphiphilic 1,1'-binaphthylpeptidomimetics developed earlier that showed promise in an in vivo murine CDI model we have synthesized related compounds with an -arytriazole or -naphthyltriazole moiety instead of the 1,1'-biphenyl or 1,1'-binaphthyl moiety.

Rhodium-catalysed tetradehydro-Diels-Alder reactions of enediynes a rhodium-stabilized cyclic allene.

Efficient methods for the synthesis of fused-aromatic rings is a critical endeavour in the creation of new pharmaceuticals and materials. A direct method for preparing these systems is the tetradehydro-Diels-Alder reaction, however this is limited by the need for harsh reaction conditions. A potential, but underdeveloped, route to these systems is transition metal-catalysed cycloaromatisation of ene-diynes.

Palladium-Catalyzed Formal (3 + 2) Cycloaddition Reactions of 2-Nitro-1,3-enynes with Vinylaziridines, -epoxides, and -cyclopropanes.

A two-step Pd-catalyzed (3 + 2) cycloaddition/HNO elimination reaction sequence has been developed to give novel cyclic 1,3-dien-5-yne systems from Pd-stabilized zwitterionic 1,3-dipoles and 2-nitro-1,3-enyne substrates. The process is highly atom-efficient and tolerates the reaction of 2-vinyloxirane, 1-tosyl-2-vinylaziridine, and diethyl 2-vinylcyclopropane-1,1-dicarboxylate derived 1,3-dipoles with a variety of 2-nitro-1,3-enyne substrates. The stereochemistry of the intermediate (3 + 2) cycloadducts was determined by single crystal X-ray analysis.

Cytotoxicity and Nitric Oxide Production Inhibitory Activities of Compounds Isolated from the Plant Pathogenic Fungus sp.

Chemical investigation of the mycelia of the pathogenic fungus sp. which was isolated from a leaf of (crowfoot grass), resulted in the isolation of a new compound, curvulariahawadride (5), along with five known compounds (1-4, and 6). Their structures were determined on the basis of spectroscopic data, including 1D and 2D NMR and HRESIMS.

Daldiniaeschsone A, a Rare Tricyclic Polyketide Having a Chromone Unit Fused to a -Lactone and Its Symmetrical Biphenyl Dimer, Daldiniaeschsone B, from an Endophytic Fungus SDBR-CMUNKC745.

Daldiniaeschsone A (), a rare tricyclic polyketide having a chromone unit fused to a -lactone and its symmetrical 6,6'-biphenyl dimer, daldiniaeschsone B (), together with three known compounds (-), were isolated from a plant-derived endophytic fungus, SDBR-CMUNKC745. Their structures were elucidated by extensive 1D and 2D NMR spectroscopic data and HRESIMS. All compounds showed -glucosidase inhibitory activity with IC values ranging from 0.

Antidiabetic and antimicrobial flavonoids from the twigs and roots of (Hassk.) Merr.

The phytochemical investigation of the twig and root extracts of (Hassk.) Merr. (Fabaceae) resulted in the isolation and identification of a new pterocarpan, erythrinocarpan (), along with 27 known compounds (-).