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.

An investigation of the allylation cascade reactions of substituted indigos.

In a continuation of the exploration of indigo cascade reactions, a series of -OMe, -Ph, -Br and -NO substituted indigos 1a-i were synthesised to probe electronic effects upon the outcome of allylation cascade reactions. When indigos 1a-i in the presence of base were reacted with allyl bromide, spiroindolinepyridoindolones 17-25 (36-75%) were obtained as the major products in each case, marking a shift in outcome relative to that previously reported for unsubstituted indigo. In electron-rich derivatives (-OMe, -Ph), -allylspiroindolinepyridoindolediones 26-29 (3-11%) were also isolated, which are most likely formed a Claisen rearrangement of the respective spiroindolinepyridoindolones 18-21.

The Detosylation of Chiral 1,2-Bis(tosylamides).

The deprotection of chiral 1,2-bis(tosylamides) to their corresponding 1,2-diamines is mostly unsuccessful under standard conditions. In a new methodology, the use of Mg/MeOH with sufficient steric additions allows the facile synthesis of 1,2-diamines in 78-98% yields. These results are rationalized using density functional theory and the examination of inner and outer-sphere reduction mechanisms.

Nickel(II) Complex with a Flexidentate Ligand Derived from Acetohydrazide: Synthesis, Structural Characterization and Hirshfeld Surface Analysis.

The mononuclear Ni(II) complex [Ni(Lp)2(CH3OH)2]Cl2 has been synthesized by reacting 1-(5-hydroxy-3-methyl-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one ligand (HL) with NiCl2·6H2O in methanol solution. In the reaction, the tridentate ligand, HL, was converted in situ into 4-hydroxy-4-phenylbut-3-en-2-ylidene)acetohydrazid ligand, (pyrazole, Lp). The pyrazole ligand acts as bidentate neutral ligand and the hydroxyl group is left uncoordinated.

Gold(I)-Catalyzed Intramolecular Hydroarylation of Phenol-Derived Propiolates and Certain Related Ethers as a Route to Selectively Functionalized Coumarins and 2-Chromenes.

Methods are reported for the efficient assembly of a series of phenol-derived propiolates, including the parent system , and their Au(I)-catalyzed cyclization (intramolecular hydroarylation) to give the corresponding coumarins (e.g., ).

Synthesis of spirocyclic heterocycles from α,β-unsaturated -acyliminium ions.

The reactions of α,β-unsaturated N-acyliminium ions, generated in situ from 4(S)-O-substitutedhydroxy-5-hydroxy-5-vinyl-N-alkylpyrrolidin-2-ones, with allylsilanes and indoles leading to the formation of spirocyclic heterocycles, are reported. Six single crystal X-ray structures and extensive 2D NMR experiments confirmed the structures and stereochemistries of these products. In addition, computational studies provided mechanistic insights and an understanding of the stereochemical outcomes of these reactions.

High-Pressure-Promoted and Facially Selective Diels-Alder Reactions of Enzymatically Derived -1,2-Dihydrocatechols and Their Acetonide Derivatives: Enantiodivergent Routes to Homochiral and Polyfunctionalized Bicyclo[2.2.2]octenes.

-1,2-Dihydrocatechols (X = Me and Cl), which are available in the homochiral form through the whole-cell biotransformation of toluene and chlorobenzene, respectively, undergo Diels-Alder cycloaddition reactions with a range of electron-deficient dienophiles at 19 kbar (1.9 GPa). The favored products of such reactions are adducts of the general form and that arise through the operation of a contrasteric or syn-addition pathway.

The Cascade Reactions of Indigo with Propargyl Substrates for Heterocyclic and Photophysical Diversity.

The synthesis of structurally diverse heterocycles for chemical space exploration was achieved via the cascade reactions of indigo with propargylic electrophiles. New pyrazinodiindolodione, naphthyridinedione, azepinodiindolone, oxazinoindolone and pyrrolodione products were prepared in one pot reactions by varying the leaving group (-Cl, -Br, -OMs, -OTs) or propargyl terminal functionality (-H, -Me, -Ph, -Ar). Mechanistic and density functional theory studies revealed that the unsaturated propargyl moiety can behave as an electrophile when aromatic terminal substitutions are made, and therefore competes with leaving group substitution for new outcomes.

Isolation of CFTR and TMEM16A inhibitors from Neorautanenia mitis (A. Rich) Verdcourt: Potential lead compounds for treatment of secretory diarrhea.

A phytochemical study on the root extracts of Neorautanenia mitis, a Nigerian medicinal plant used in the management of diarrhea, led to the isolation of one new and 19 known natural products. These compounds and crude extracts were evaluated for Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl channel and calcium-activated Cl channel (TMEM16A) inhibitory activities in T84 and Calu-3 cells, respectively. Four compounds namely dolineon, neodulin, pachyrrhizine, and neotenone inhibited cAMP-induced Cl- secretion across T84 cell monolayers with IC values of ~0.

Iterative Suzuki-Miyaura Cross-coupling/Bromo-desilylation Reaction Sequences for the Assembly of Chemically Well-defined, Acyclic Oligopyrrole/Benzenoid Hybrids Embodying Mixed Modes of Connectivity.

Syntheses of a range of chemically well-defined oligopyrrole/benzenoid hybrids are described using tandem Suzuki-Miyaura cross-coupling/bromo-desilyation reaction sequences for linking borylated pyrroles, halogenated pyrroles and/or dibromobenzenes to one another. By such means, including iterative variants, a range of all α-linked, all β-linked oligopyrroles as well as certain combinations thereof have been assembled, some of them for the first time. The conductivities of iodine-treated thin films formed from certain such systems have been determined.

The effect of isomerism and other structural variations on the G-quadruplex DNA-binding properties of some nickel Schiff base complexes.

A series of novel isomeric nickel Schiff base complexes, as well as nickel complexes of related ligands having asymmetric structures have been prepared and characterised using microanalysis, 1H and 13C NMR spectroscopy and ESI-MS. The Schiff base ligands were prepared by condensation reactions involving ethylenediamine and different derivatives of benzophenone. The solid-state structures of eight of the complexes were also determined and revealed that each possessed a regular square planar coordination geometry around the metal ion.

In Search of Fulminate Analogues: L M≡CP=NR.

The "CPNR" ligand may be viewed as being isolobal with fulminate, CNO; however, attempts to prepare a complex of such a ligand resulted instead in a range of novel imino and aminophosphinocarbyne complexes. Sequential treatment of [Mo(≡CBr)(CO) (Tp*)] (Tp*=hydrotris(dimethylpyrazolyl)borate) with nBuLi and ClP=NMes* (Mes*=C H tBu -2,4,6) afforded mixtures of the complexes [Mo(≡CPnBuNHMes*)(CO) (Tp*)] and traces of the bimetallic products [Mo {μ -C P O(NHMes) }(CO) (Tp*) ] and [Mo (μ -C PNHMes)(CO) (Tp*) ]. The reaction of [W(≡CBr)(CO) (Tp*)] with nBuLi and ClP=NMes* afforded predominantly the mononuclear carbyne [W{≡CP(=NMes*)nBu })(CO) (Tp*)] and traces of the binuclear complex [W (μ-C PNHMes)(CO) (Tp*) ] which is also obtained when tBuLi is used.

A new class of quadruplex DNA-binding nickel Schiff base complexes.

We have prepared six new nickel Schiff base complexes via reactions of substituted benzophenones with different diamines in the presence of nickel(ii). These new complexes were then reacted with 1-(2-choroethyl)piperidine to afford a further six novel nickel(ii) Schiff base complexes bearing pendant ethylpiperidine groups. The complexes bearing the ethylpiperidine moieties had greater solubility in water, and were therefore suitable for use in DNA binding experiments.

Regioselective convergent synthesis of 2-arylidene thiazolo[3,2-]pyrimidines as potential anti-chikungunya agents.

Convergent and convenient regioselective synthesis of novel thiazolo[2,3-]pyrimidine derivatives was accomplished using the one-pot reaction of 6-ethylthiouracil, bromoacetic acid, anhydrous sodium acetate, acetic anhydride, acetic acid and suitable aldehyde. X-ray crystallographic study reveals the presence of the configuration of only one regioisomer confirmed by computational studies as being the most likely isomer present.

Styryllactones from Goniothalamus tamirensis.

The phytochemical investigation of the twig and leaf extracts of Goniothalamus tamirensis led to the isolation and identification of 15 compounds including three rare previously undescribed styryllactones, goniotamirenones A-C, together with 12 known compounds. (Z)-6-Styryl-5,6-dihydro-2-pyranone and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one are reported here for the first time as previously undescribed natural products. Their structures were elucidated by spectroscopic methods.

Syntheses of Dimethyl (1,2)-3-Bromocyclohexa-3,5-diene-1,2-dicarboxylate and Its Enantiomer.

The title compounds, (-)- and (+)-, representing potentially valuable building blocks for chemical synthesis, have each been prepared from cyclopentanone in eight steps. The pivotal one involves a resolution, through the quinine- or quinidine-promoted methanolysis of the cyclic anhydride (±)-, leading to chromatographically separable pairs of enantiomerically pure forms of regioisomeric methyl half esters.

Relative hemilabilities of HB(az) (az = pyrazolyl, dimethylpyrazolyl, methimazolyl) chelates in the complexes [M(η-CH)(CO){HB(az)}] (M = Mo, W).

The reactions of [M(η3-C3H5)Br(CO)2(NCMe)2] (M = Mo, W) or [Mo(η3-C3H5)Br(CO)2(PMe2Ph)2] with Na[H2B(mt)2] (mt = methimazolyl) affords the complexes [M(η3-C3H5)(CO)2{κ3-H,S,S'-H2B(mt)2}], the 3-centre, 2-electron B-H-M interaction of which was found to be inert with respect to opening under mild conditions, while more forcing conditions (heating with PMe2Ph) resulted in cleavage of the entire allyl and borate ligands to form [Mo(CO)3(PMe2Ph)3]. In contrast, the reaction of [Mo(η3-C3H5)Br(CO)2(NCMe)2] with Na[H2B(pz)2] affords either [Mo(η3-C3H5)(CO)2{κ3-H,N,N'-H2B(pz)2}] or (more likely) [Mo(η3-C3H5)(CO)2(NCMe){κ2-N,N'-H2B(pz)2}] which in turn reacts with phosphines to provide [[Mo(η3-C3H5)(CO)2(PPhR2){κ2-N,N'-H2B(pz)2}] (R = Me, Ph). The reactions discussed indicate the propensity for 3-centre, 2-electron B-H-Mo interactions increases in the order H2B(pz)2 < H2B(pz*)2 < H2B(mt)2 (pz* = 3,5-dimethypyrazolyl).

Anion Modulated Structural Variations in Copper(II) Complexes with a Flexidentate Ligand Derived from 2-((2-aminoethyl)amino)ethan-1-ol: Synthesis and Spectroscopic and X-ray Structural Characterization.

Flexidentate ligand, HL has been prepared by the condensation of aminoethylethanolamine (AEEA) with benzoylacetone (bezac). On reaction with copper(II) salts it gives complexes CuLClO4.H2O (1), CuLN3 (2) and [Cu3L3Br]Br2.

Total Syntheses of the 3-Pyrrolo[2,3-]quinolone-Containing Alkaloids Marinoquinolines A-F, K, and Aplidiopsamine A Using a Palladium-Catalyzed Ullmann Cross-Coupling/Reductive Cyclization Pathway.

Compounds - and representing key members of the marinoquinoline family of natural products, together with the related marine alkaloid aplidiopsamine A (), have been synthesized using various combinations of palladium-catalyzed Ullmann cross-coupling and reductive cyclization processes involving a C3-arylated pyrrole as the common intermediate. These natural products have been characterized by single-crystal X-ray analyses and evaluated as inhibitors of acetylcholinesterase (AChE) with congener proving to be the most active.

Desymmetrization Reactions of Indigo with Grignard Reagents for the Synthesis of Selective Antiplasmodial [1,3']-3-Aryl-2,2'-diindol-3'-ones.

The nucleophilic addition of organomagnesium and organolithium species to the cheap and robust natural dye indigo led to desymmetrization of the heterocyclic nucleus via a Grignard addition-dehydration procedure. Twenty-seven diversely functionalized [1,3']-3-substituted 2,2'-diindol-3'-ones were synthesized by this methodology, with several showing submicromolar inhibition and exquisite selectivity against parasites (3D7 and Dd2 strains) . This work demonstrates the utility of indigo dye as a highly versatile scaffold for the synthesis of structurally diverse, bioactive heterocycles.

1,2-Addition versus homoconjugate addition reactions of indoles and electron-rich arenes to α-cyclopropyl N-acyliminium ions: synthetic and computational studies.

An investigation of the reactivity of α-cyclopropyl N-acyliminium ions towards indoles has resulted in the unprecedented synthesis of 5-cyclopropyl-5-(3-indoyl)pyrrolidin-2-ones via 1,2-addition reactions and, in the case of highly electron deficient indoles and electron rich arenes, spiroheterocycles via sequential homoconjugate and 1,2-addition reactions with often high diastereoselective control at the C-5 quaternary stereocentres. Computational studies provided support for the proposed mechanisms and stereochemical outcome of these reactions, clearly showing that the 1,2-addition pathway is kinetically controlled. In reactions where the 1,2-adduct is destabilised, for example when the arene ring is less nucleophilic, the 1,2-addition is reversible and the thermodynamically preferred homoconjugate addition and subsequent rearrangement and cyclisation reactions become the major pathway.

Highly diastereoselective synthesis of enantioenriched anti-α-allyl-β-fluoroamines.

A highly diastereoselective synthesis of anti-α-allyl-β-fluoroamines has been developed involving enantioselective α-fluorination of aldehydes followed by a diastereoselective Petasis allyl borono-Mannich reaction. The products are obtained generally in good overall yields for the two steps and with drs of 97 : 3-99 : 1 and ees of 86-92%. Selected products were converted to 3-, 5- and 6-membered ring heterocycles, the latter two types incorporating an exo-cyclic fluorine.

Application of Electrocyclic Ring-Opening and Desymmetrizing Nucleophilic Trappings of meso-6,6-Dibromobicyclo[3.1.0]hexanes to Total Syntheses of Crinine and Haemanthamine Alkaloids.

The thermally induced electrocyclic ring-opening of C-symmetric ( meso) 6,6-dibromobicyclo[3.1.0]hexanes such as 10 in the presence of the chiral, nonracemic 1°-amine 28 afforded a ca.