On the stereostructures of (+)-eupenoxide and (−)-3′,4′-dihydrophomoxide: a caveat on the spectral comparisons of oxygenated cyclohexenoids

The structural ambiguity surrounding the structure of eupenoxide has been clarified and the absolute configuration of this natural product has been assigned. It is firmly established that ‘eupenoxide’ recently reported by Liu et al. is in fact a new natural product, (−)-3′,4′-dihydrophomoxide. The NMR spectra of these polyoxygenated cyclohexenoids exhibit subtle solvent, concentration, and temperature dependent variations, and due caution should be exercised when making spectral comparisons for structural assignments.     

An efficient asymmetric synthesis of grenadamide

The cyclopropane containing natural product grenadamide has been prepared in six steps using (R)-5,5-dimethyl-oxazolidin-2-one as a chiral auxiliary for asymmetric synthesis. Key synthetic steps include the use of the β-hydroxyl group of a syn-aldol product as a ‘temporary’ stereocentre to control the facial selectivity of a directed cyclopropanation reaction, as well as the use of phenylethylamine as a nucleophile for the direct aminolysis of an N-acyl-oxazolidin-2-one intermediate.     

Total synthesis of novel bioactive natural product paracaseolide A and analogues: computational evaluation of a ‘proposed’ biomimetic Diels–Alder reaction

A short and generally applicable synthesis of bioactive tetracyclic natural product paracaseolide A has been accomplished employing a ‘proposed’ biomimetic Diels–Alder reaction as the key strategic step. The Diels–Alder precursors for this purpose were readily assembled through a versatile Suzuki coupling on preformed α-halo butenolides. The mechanistic aspects of the ‘putative’ biomimetic Diels–Alder reaction have been probed using computational methods, which suggest that this [4+2]-cycloaddition proceeds through a step-wise process and product profile is thermodynamically governed.     

The absolute configuration of streptonigrin

A theoretical study of the molecular circular dichroism (CD) of the antitumor antibiotic natural product streptonigrin is described, aiming at the secure assignment of its absolute configuration by comparison of the CD spectra predicted for M and P, with the experimental one. The stereostructure of streptonigrin was previously investigated by two other groups, yet leading to two different attributions. Although streptonigrin possesses two biaryl axes, only the ‘southern’ one is configurationally stable and thus responsible for the chiroptical properties, since the ‘northern’ AB-ring system of the molecule is kept in plane with ring C by hydrogen bonding. All computational methods applied within this work to simulate the CD spectrum—semiempirical approaches and time-dependent density functional theory (TDDFT)—consistently attribute the M-configuration to streptonigrin.     

Synthesis of seco-psymberin/irciniastatin A: the discovery of a novel PhI(OAc)2 mediated cascade cyclization reaction

The psymberin unsaturated ‘psymberate’ side chain 7 was synthesized in 7 steps (36% yield) with good diastereoselectivity using commercially available starting material to control the stereochemistry at C₄ and C₅. The synthesis of seco-psymberin was completed in an efficient manner based on a CuI mediated coupling reaction between vinyl iodide 8 and ‘psymberamide’ 7. In an attempt to synthesize natural psymberin from the seco-intermediate, a novel PhI(OAc)₂ mediated cascade ring closing reaction was discovered. A possible mechanistic pathway for the formation of the ring closing product was presented.     

Reactivity and regioselectivity in the synthesis of spiroindoles via indole o-quinodimethanes. An experimental and computational study

The 1,3-dipolar cycloaddition reactions of stable nitrile oxides with indole o-quinodimethanes have been examined. In all cases the ‘exo-anti’ addition products, dispiroisoxazolines, were isolated in moderate to good yields (25-47%). In addition, from the reaction of one of the indole quinodimethanes with mesitonitrile oxide the ‘exo-syn’ addition product was isolated in 7% yield along with the remarkable indole quinodimethane dimerization and cycloaddition product, which was isolated in 13% yield. An analogous dimerization and cycloaddition product was isolated in 18% yield from the reaction of the N-acetyl-indole quinodimethane with mesitonitrile oxide. In the case of the reaction of the N-benzoylindole quinodimethane with the 2,6-dichlorobenzonitrile oxide an oxime was also isolated in 13% yield. The proposed reaction mechanism is supported by semiempirical (AM1) MO calculations via FMO interactions. The observed selectivity was explained by an investigation of the transition states carried out also for analogous dispiroisoxazolines.     

An expedient synthesis of (±)-centrolobine

An expedient synthesis of the antibiotic natural product centrolobine is reported, the key step being the one pot, multi-component construction of a tetrahydropyran-4-one via a ‘revisited’ Maitland-Japp reaction.     

Total synthesis of (+)-blastmycinone and formal synthesis of (+)-antimycin A3b

The formal synthesis of (+)-antimycin A_3b and the total synthesis of (+)-blastmycinone were achieved using, as a key step, a method developed by us for the synthesis of 2-methyl-1,3-diols via Ti(III)-mediated diastereo- and regioselective opening of trisubstituted 2,3-epoxy alcohols, to carry out the stereoselective construction of the hydroxy-acid segment. An interesting intramolecular radical translocation took place during the epoxide opening process transforming its vicinal PMB-ether in situ, into an ‘1,2-O-(p-methoxy)benzylidene’ ring.     

Synthetic studies on the phorboxazoles: a short synthesis of an epi-C23 tetrahydropyran core

Studies on the synthesis of the anticancer natural products, the phorboxazoles have led to the synthesis of the C21-C32 penta-substituted tetrahydropyran core which is epimeric to the natural product at C23. The synthesis was achieved in only seven linear steps. The key steps were the use of a Masamune-Abiko anti-aldol reaction, the formation of a dihydropyran precursor molecule by the use of a new ‘Maitland-Japp-like’ cyclisation, and a highly diastereoselective reductive alkylation of the dihydropyran double bond, to generate the corresponding tetrahydropyran ring in an excellent yield.     

E/Z product distribution in the metathesis of allyl alcohol derivatives with a first generation ruthenium-based catalyst

Based on experiments with four simple derivatives of allyl alcohol, it has been shown that the product of cross-metathesis as mediated by a ‘first generation’ ruthenium catalyst increases in its proportion of the E-isomer as the reaction progresses. This increase is due to equilibration, which is also mediated by the ruthenium catalyst.     

H-quadrupolar coupling-based analysis of stereochemical and regiochemical memory in the Pd-catalysed allylic alkylation of iso-cinnamyl type substrates employing the chiral monophosphine ligands ‘MOP’ and ‘MAP’

The reaction of iso-cinnamyl acetate with NaC(Me)(CO₂Me)₂, catalysed by Pd-‘MOP’ (MOP=2-methoxy-2′-diphenylphosphino-1,1′-binaphthalene) is known to proceed with a regiochemical memory effect that results in the predominant generation of the branched alkylation product. The analogous reaction employing ‘MAP’ as ligand (MAP=2-N,N-dimethylamino-2′-diphenylphosphino-1,1′-binaphthalene) proceeds with ‘normal’ regioselectivity to generate predominantly the linear isomer of product. A ²H-NMR based analysis, employing quadrupolar coupling in a chiral liquid crystal matrix, has been developed to facilitate the simultaneous study of the regiochemical and stereochemical outcome of the reaction of both enantiomers of iso-cinnamyl ester substrates in ²H-labelled but racemic samples. The analysis allows the comparison of relative rates of two competing isomerisation processes occurring in the π-allyl intermediates in the Pd-catalysed reaction, one of which facilitates asymmetric induction, the other resulting in loss of regiochemical memory. It is demonstrated that the two processes are partially coupled and that this then limits the attainment of high global enantiomeric excess in the branched product to reactions that proceed with low regiochemical retention. A key factor for the observation of high regiochemical memory is found to be the nucleophilicity of the malonate anion and the electrophilicity of the Pd-π-allyl intermediate with reduction in the reactivity of either partner resulting in the onset of substantial loss of memory.     

Stereoselectivity in the organoiron-mediated synthesis of (±)-mesembrine

The preparation and structural characterisation of a 1-aryl-substituted electrophilic η⁵-cyclohexadienyliron complex with the correct functionalisation as a ‘C₁₂ building block’ for the synthesis of (±)-mesembrine establishes the accessibility of a flattened conformation to allow nucleophile addition ipso to the arene. The chirality relay in quaternary centre formation by nucleophile addition has been confirmed, and the product has been converted into the Sceletium alkaloid mesembrine.     

Application of probabilistic neural networks in qualitative analysis of near infrared spectra: determination of producing area and variety of loquats

Near infrared (NIR) spectra of a sample can be treated as a signature, allowing samples to be grouped on basis of their spectral similarities. Near infrared spectroscopy (NIRS) combined with probabilistic neural networks (PNN) have been used to discriminate producing area and variety of loquats. Two varieties of loquats (‘Dahongpao’ and ‘Jiajiaozhong’) picked from two producing areas of ‘Tangxi’ and ‘Cunan’ in Zhejiang province were analyzed in this study. Principal component analysis (PCA) was applied before PNN modeling and the results indicated that the dimension of the vast spectral data can be effectively reduced. For each model, half samples were used to train the network and the remaining half were used to test the network. The results of the PCA-PNN models for discriminating the variety of samples from the same producing area or for discriminating the producing area of the same variety samples were much better than those of the PCA-PNN models for discriminating variety or producing area of all loquat samples. The results of this study show that NIRS combined with PCA-PNN is a feasible way for qualitative analysis of discriminating fruit producing areas and varieties.     

Acceleration of Cu(I)-mediated Huisgen 1,3-dipolar cycloaddition by histidine derivatives

Acceleration of Cu(I)-mediated Huisgen 1,3-dipolar cycloaddition (Sharpless ‘click reaction’) by non-basic histidine derivatives was found. An efficient ‘self-activating’ click reaction between the azide- and acetylene-containing peptides on the solid-phase has also been achieved by introducing the N^im-benzylhistidine residue on the reacting peptides.     

Synthesis of (+)-agelasine C. A structural revision

An efficient synthesis of (+)-agelasine C has been achieved from ent-halimic acid. The structure and absolute configuration of the natural product (−)-agelasine C was established and a structure for epi-agelasine C, is proposed.     

The assessment of π-π selective stationary phases for two-dimensional HPLC analysis of foods: Application to the analysis of coffee

Differences between alkyl, dipole-dipole, hydrogen bonding, and π-π selective surfaces represented by non-resonance and resonance π-stationary phases have been assessed for the separation of ‘Ristretto’ café espresso by employing 2DHPLC techniques with C18 phase selectivity detection. Geometric approach to factor analysis (GAFA) was used to measure the detected peaks (N), spreading angle (β), correlation, practical peak capacity (n_p) and percentage usage of the separations space, as an assessment of selectivity differences between regional quadrants of the two-dimensional separation plane. Although all tested systems were correlated to some degree to the C18 dimension, regional measurement of separation divergence revealed that performance of specific systems was better for certain sample components. The results illustrate that because of the complexity of the ‘real’ sample obtaining a truly orthogonal two-dimensional system for complex samples of natural origin may be practically impossible.     

‘O-Acyl isopeptide method’ for the efficient synthesis of difficult sequence-containing peptides: use of ‘O-acyl isodipeptide unit’

A novel ‘O-acyl isodipeptide unit’, Boc-Thr(Fmoc-Val)-OH 5 has been successfully used for the efficient synthesis of a difficult sequence-containing pentapeptide based on the ‘O-acyl isopeptide method’, in which racemization-inducible esterification could be omitted, suggesting that the use of O-acyl isodipeptide units allows the application of this method to fully automated protocols for the synthesis of long peptides or proteins.     

Synthetic aspects of the oxidative amidation of phenols

The oxidative amidation of phenols effects the conversion of appropriately substituted phenols into 4-amidodienones (‘para-oxidative amidation’) or 2-amidodienones (‘ortho-oxidative amidation’) by the action of hypervalent iodine reagents. The reagent, (diacetoxyiodo)benzene (‘DIB’) is especially effective in these transformations. This paper focuses on techniques for the desymmetrization of the dienoes thus obtained, leading to the stereocontrolled creation of N-substituted spiro carbons. The methodology creates new opportunities in alkaloid synthesis, as apparent from a number of examples.     

Dipyridinocalixcrown/diiodoperfluorocarbon binary host systems for CsI: structural studies and fluorous phase extraction of caesium

A mixture of partial cone 2,4-bis[(2-pyridylmethyl)oxy]-(1,3)-p-tert-butylcalix[4]crown-6, hexadecafluoro-1,8-diiodooctane and CsI in EtOH produces a crystalline ‘supramolecular salt’. In the solid state the caesium ion of the ‘supercation’ is encapsulated inside the cavity created by the crown ether loop, the picolyl and the inverted phenyl moieties, while the two iodide ions of the ‘superanion’ form a discrete five-component aggregate held together by co-existing hydrogen and halogen bonds. Similar calix/CsI/iodofluorocarbon adducts are shown to exist also in solution. In a prototypical study, a combination of this calixcrown and liquid octafluoro-1,4-diiodobutane acts as an effective ‘binary host’ system for the selective extraction of CsI from aqueous to fluorous phase.