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The structure of the dimeric phloroglucinol natural product pilidiostigmin, previously reported from the leaves of the Australian rainforest plant Pilidiostigma glabrum, has been revised based on reinterpretation of the spectroscopic data. Pilidiostigmin is an oxidised diacyldibenzofuran. ROESY exchange correlations indicate that pilidiostigmin occurs in solution as an almost equimolar mixture of two interconverting 3-hydroxycyclohexenone tautomers.

Two new secondary metabolites, the xylerythrin derivative dragmacidol A (1) and the steroid dragmacidolide A (2), were isolated from a specimen of the marine sponge Dragmacidon australe, collected off the coast of the Whitsunday Islands in Queensland, Australia. Their structures were fully characterized via analysis of 1D/2D NMR and MS data. The proton-poor structure of 1 was also supported through successful 13C DFT-NMR calculations. The isolation of these two metabolites from this sponge genus is quite unusual, given that previous reports of Dragmacidon secondary metabolites have been dominated by indole and β-carboline alkaloids.

Negishi coupling is one of the most important modern organic synthetic methods for selective C–C bond formation, and has been extensively applied in the synthesis of organic electronic, optical, electrochemical, and magnetic materials. This report provides a critical overview of the efficiency and versatility of Negishi coupling as applied for synthesizing polymers, oligomers, and small molecules with a wide variety of structural features and various desirable functions for organic electronic, optoelectronic, and other advanced technologies.

A modular sequence to construct isoflavones with a range of methoxy-substituted aryl substituents is presented.

It is proposed that sulfenate anions generated from sulfoxides act as catalysts in the base promoted conversion of benzyl halides into trans-stilbenes.

The usability of the title complexes is shown in several asymmetric and mechanistically diverse reactions including Michael additions, aza-Michael additions, and direct Aldol reactions.

A general method for the Pd-catalyzed allylic substitution with diarylmethane derivatives is reported.

P,N ligands are an important class of ligands for asymmetric catalysis. In this tutorial review an up to date account of recent applications of these ligands in asymmetric catalysis is presented. A special focus is given to newer classes of ligands and the application of more established P,N ligands in novel reactions.

A novel retrosynthetic disconnection for the stereoselective preparation of α,α′-dioxygenated carbonyl compounds is disclosed. Herein we report a method to divert the oxidation of vinyl boronate esters from the B–C bond to the CC bond, resulting in a new stereoselective class of oxidation products from vinyl boronate esters. Treatment of 2-B(pin)-substituted allylic alcohols with catalytic OV(acac)2 and TBHP resulted in a highly chemo- and diastereoselective directed epoxidation to provide B(pin)-substituted epoxy alcohols (55–96% yield, dr > 20 : 1). In the case of B(pin)-substituted bis-allylic alcohols, highly substituted bis-epoxy alcohols with five contiguous stereocenters were obtained (dr > 20 : 1). Furthermore, the difference in reactivity between allylic alcohols and 2-B(pin)-substituted allylic alcohols towards epoxidation enabled the selective oxidation of the allylic alcohol in the presence of TBHP and VO(acac)2. The reactivity difference between the two allylic alcohols suggests CCB(pin) to be more electron deficient than CC(alkyl). The B(pin)-substituted epoxy alcohols are also useful synthetic intermediates. Tandem vanadium catalyzed epoxidation of the 2-B(pin)-substituted allylic and bis-allylic alcohols with excess TBHP generated the intermediate epoxides and bis-epoxides, respectively. Subsequent addition of NaOH resulted in the oxidation of the B–C bond of the B(pin)-substituted epoxides to afford 2-keto-anti-1,3-diols (60–83% yield) and epoxide-substituted 2-keto-anti-1,3-diols (60–78% yield, dr > 20 : 1). The latter underwent a novel facile acid-mediated cyclization to furnish fully substituted dihydroxy-tetrahydrofuran-3-ones (65–91% yield, dr > 20 : 1). Such compounds are difficult to efficiently access via conventional synthetic methods.

The aim of this perspective is to critically review the three most prominent bioorthogonal reactions that are used presently, on both a purely chemical level and in the context of biological systems. This includes the uses both for synthesis of therapeutic molecules, modification of large biomolecules or antibodies, and in particular, the exciting use in the field of 'pre-targeting', for both possible treatment and imaging technologies. We will compare the validity of each reaction when compared to others, and their usefulness in biological systems, as each methodology has clear advantages over the others in differing environments.

The first practical preparation of the title reagents, from readily available starting materials, is described.

An unusual chelation-controlled pathway is revealed based on experimental and computational investigations: binding of the α-chloro aldimines N,O and Cl atom to zinc reverses the selectivity predicted by the Cornforth—Evans model.

The development of new transition-metal-catalyzed crosscoupling methods has been a focus of intense research. More recently, direct arylations are emerging as a more efficient method to C C bond formations. Certain types of C H bonds, however, have proven difficult to arylate, and represent a particular challenge for asymmetric processes. We envisioned a novel and potentially very powerful dual catalyst cycle for the enantioselective functionalization of very weakly acidic benzylic C H groups (Scheme 1). The left-hand cycle

In the presence of different oxidants (O2/Co(II)-catalyst, IBX, PhI(OAc)2), the title binaphthols are converted to the quinone derivatives.

Aminohydroxy ketones (IX) can be generated with high diastereoselectivity by a one-pot two-step process including aziridination followed by B—C bond oxidation.

Chemoenzymatic syntheses of key intermediates (II) and (VI) in the preparation of the potent β-3 receptor agonist (VI) are described.

The VO(acac)2-catalyzed oxidations proceed under neutral conditions with excellent diastereoselectivity to give the epoxides (II).

The scope of the novel chiral ligand ADA is evaluated in the catalytic asymmetric addition of ZnEt2 to ketones.

An improved synthesis of phenylethynyl[1,2,4]methyltriazinesis described. In this method, 5-methyl-3-methyl-thio[1,2,4]triazineis cross-coupled with various phenylacetylenes using microwave conditionsto produce phenylethynyl[1,2,4]methyltriazinesin increased yields. Interest in the phenylethynyl[1,2,4]methyltriazinescaffold stems from recent reports demonstrating their potency asmGluR5 antagonists.

A polyaromatic alkaloid, aplidiopsamine A was isolated from the temperate Australian ascidian, Aplidiopsis confluata, and its structure was determined from interpretation of mass, 1D and 2D NMR spectra. Aplidiopsamine A is the first alkaloid to possess the tricyclic aromatic substructure 3H-pyrrolo[2,3-c]quinoline conjugated to an adenine. Aplidiopsamine A exhibited significant inhibition of growth of chloroquine resistant and sensitive strains of the malaria parasite, Plasmodium falciparum, and minimal toxicity toward human cells.

This critical review will focus on the application of shape-persistent receptors for anions that derive their rigidity and optoelectronic properties from the inclusion of arylethynyl linkages. It will highlight a few of the design strategies involved in engineering selective and sensitive fluorescent probes and how arylacetylenes can offer a design pathway to some of the more desirable properties of a selective sensor. Additionally, knowledge gained in the study of these receptors in organic media often leads to improved receptor design and the production of chromogenic and fluorogenic probes capable of detecting specific substrates among the multitude of ions present in biological systems. In this ocean of potential targets exists a large number of geometrically distinct anions, which present their own problems to the design of receptors with complementary binding for each preferred coordination geometry. Our interest in targeting charged substrates, specifically how previous work on receptors for cations or neutral guests can be adapted to anions, will be addressed. Additionally, we will focus on the design and development of supramolecular arylethynyl systems, their shape-persistence and fluorogenic or chromogenic optoelectronic responses to complexation. We will also examine briefly how the “chemistry in the cuvet” translates into biological media (125 references).

Three novel rearrangement products, (III),(IV), and (VIII), are derived from substrates belonging to the furoquinoline class.

A new route is presented to synthesize pyrrole 2-carboxylates, pharmaceutically important substructures, via cyclocondensation of salts (I) with glycine esters.

Chemical investigation of the Australian ascidian Aplidium altarium led to the isolation of two new tyrosine derivatives, botryllamides K (1) and L (2), together with six known metabolites, botryllamides A–C (3–5), botryllamide G (6) and perspicamides A (7) and B (8). The structures of these compounds were elucidated by spectroscopic analysis. This is the first reported chemistry from this species. Compounds 1–8 were evaluated for their cytotoxicity towards the tumour cell lines, MCF-7 (breast), H460 (lung) and SF268 (central nervous system).

A novel five-step sequence for the synthesis of genistein (VIb) from ketone (Ia) involves formation of the enamino ketone (III) followed by ring closure and Suzuki coupling.

The x-ray crystal structures forcis,cis- andtrans,trans- 2,3-dimethyl-1-nitrocyclopropanecarboxylic acid, 2,2,3,3-tetramethyl-1-nitrocyclopro-panecarbonitrile, 2,2,3,3-tetramethyl-1-nitrocyclo-propanecarboxamide, andtrans,trans,trans,trans-2,2′,3,3′-tetramethyl-1,1′-dinitrobicyclopropyl are reported. Contrary to expectations, π-accepting groups that are syn to dimethyl substituents prefer a conformation perpendicular to the three-membered ring when there is an sp2 electron-withdrawing substituent also bonded to the same carbon atom. Ab initio calculations are reported for model compounds and these results are compared with the experimentally determined ones.

Much attention has been focused recently on the stability of immunotoxin (antibody-toxin) conjugates linked by a disulfide bridge. Conflicting reports have appeared regarding the in vivo stability of such conjugates prepared with the two most commonly used cross-linking reagents, SPDP and 2-iminothiolane. We have developed (i) a series of reagents based on 2-iminothiolane substituted at the 4- and/or 5-positions (X2ITs) which, based on model studies with simple amines, should show enhanced disulfide stability when conjugated with antibodies or other proteins and (ii) a real-time method for monitoring the rate and extent of conjugation of these reagents with amino groups. Depending upon the substituent, the stability of model-activated disulfides relative to unsubstituted 2-iminothiolane was increased from 5- to 4000-fold as measured by glutathione-induced release of thionitrobenzoic acid. This family of cross-linking reagents should allow the construction of disulfide cross-linked toxin, drug, or enzyme conjugates with enhanced stability in vivo.

ion of hydrogen atoms from molecules by ground state fluorine (2P) atoms is a general method for production of free radicals. 1-4 When methoxy radicals are prepared by this method, hydroxymethyl radicals (CH20H) are produced in a competing reaction channel.415 F(2P) + CHPH products (I) F(2P) + CH 30H HF + CH 30 t:.H = -32 ± I kcaljmoJl 6•18 (Ia) F(2P) + CHPH -+ HF + CH20H t:.H = -41 ± 3 kcaljmoJI 7 (I b) No other product channels of the reaction have been observed in mass spectrometric studies.9•12•15 It is. therefore unlikely that any products other than CH30, CH20H, and HF are formed in primary processes at room temperature. Assuming this to be true, the fractional yields of each product channel, for the case of CHpH, are defined by 'Experimental work done at Naval Research Laboratory. l Permanent address: Catholic University. (2a)

Cp 2 Ta(=CH 2 )(Me) (1; Cp≡η 5 -C 5 H 5 ) reacts with relatively unhindered silanes such as Me 2 SiH 2 and Me 3 SiH in tetrahydrofuran (THF) or benzene to produce equal amounts of Cp 2 Ta(H 2 C=CH 2 )(Me) and the bis(silyl) complexes Cp 2 Ta(SiR 3 ) 2 (H) (SiR 3 =SiMe 2 H, SiMe 3 ) with concurrent liberation of methane. In contrast, 1 reacts with the indered silane H 2 Si(t-Bu) 2 in THF to yield the silyl-substituted alkylidene hydride complex Cp 2 Ta(H)(=C(H)(SiH(t-Bu) 2 )) (2) and varying amounts of the bridging alkylidene complex {CpTa(μ 2 -η 1 :η 5 -C 5 H 4 )} 2 (μ-C(H)(SiH(t-Bu) 2 )) (3) Reversible hydrogen transfer from tantalum to the alkylidene carbon in 2 is facile, and the resultant unsaturated alkyl can be readily trapped by donor ligands to produce Cp 2 Ta(L)(CH 2 SiH(t-Bu) 2 ) (4a, b; L=CO, PMe 3 ). The reaction of 1 with H 2 Si(t-Bu) 2 in benzene also produces the phenyl methylene complex Cp 2 Ta(=CH 2 )(Ph) (5) in addition to 2, as a result of competing benzene C-H activation during the reaction

The optical isomers of cis-N-normetazocine are the starting materials for the synthesis of a number of pharmacologically useful compounds. An improved resolution procedure for obtaining these isomers is reported.

A reinvestigation of the radiation protection activity of S-(2-((2{prime}-carbamylethyl)amino)ethyl) lithium hydrogen phosphorothioate (4a) revealed that this compound possessed good (70% protection at a dose of 600 mg/kg) activity. The thione and imino bioisosteres of 4, S-(2-(2{prime}-thiocarbamylethylamino)ethyl) lithium hydrogen phosphorothioate (13a) and S-(2-(2{prime}-amidinoethylamino)ethyl) phosphorothioic acid (18b) showed 100% protection at doses of 300 and 150 mg/kg, respectively. The N-methyl (4b) and tert-butyl (4c) analogues of amide 4a, the N-methyl (13b) analogue of the thioamide 13a, the N-methyl (18a) analogue of amidine (18b), and the cyclic amidine S-(2-((2{prime}-(4,5-dihydroimidozoyl)ethyl)amino)ethyl) lithium hydrogen phosphorothioate (21) all showed 80% protection at the highest dose tested.

Compounds possessing thiol, sulfide, and sulfoxide functionality attached to chiral auxiliary fragment 1 can be synthesized from halogenated aromatics 2 and 3. In the sulfoxides,auxiliary 1 can define the sulfinyl configuration in either relative sense depending on whether sulfinyl configuration is established under kinetic or thermodynamic control.