Pseudoasymmetry, stereogenicity, and the RS-nomenclature comprehended by the concepts of holantimers and stereoisograms

The concepts of holantimer and stereoisogram are applied to comprehensive discussions on the term ‘pseudoasymmetry’, where the concept of RS-stereogenicity is used as a more definite concept than usual stereogenicity. Thereby, three relationships contained in each stereoisogram can be definitely specified: an enantiomeric relationship is related to chiral/achiral, an RS-diastereomeric relationship is related to RS-stereogenic/RS-astereogenic, and a holantimeric relationship is related to scleral/ascleral, which is coined to keep the terminology in a balanced fashion. Such stereoisograms are classified into five types (Types I-V) by virtue of the three relationships. Among them, Type I, III, and V are selected as a set of RS-stereogenic units: chiral/ascleral RS-stereogenic unit (or Type I unit), chiral/scleral RS-stereogenic unit (or Type III unit), and achiral/scleral RS-stereogenic unit (or Type V unit). Thereby, the term ‘pseudoasymmetric stereogenic units’ should be replaced by the term ‘achiral/scleral RS-stereogenic units’ (or ‘Type V units’).     

‘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.     

A radical mediated first total synthesis from ‘diacetone glucose’ and determination of the absolute stereochemistry of xylobovide

The first total synthesis by an intramolecular radical cyclisation protocol on a carbohydrate derived 5-hexynyl system, and determination of the absolute stereochemistry of xylobovide are reported.     

α-(3,7-Dioxa-r-1-azabicyclo[3.3.0]oct-c-5-ylmethoxy)-diazines. Part 1: Synthesis and stereochemistry. Extension to s-triazine series

The general and efficient synthesis of the title compounds, consisting of the (selective) replacement of chlorine in commercial α-chlorodiazines and cyanuryl chloride by the 3,7-dioxa-r-1-azabicyclo[3.3.0]oct-c-5-ylmethoxy group (Williamson method) is described. The stereochemistry of this new series of derivatives is analysed in terms of different conformational chirality exhibited in solution (¹H NMR) versus solid state (X-ray diffractometry), meso against chiral forms, respectively. In solid state, the inclusion capacity of some chiral networks as well as their supramolecular aggregation is pointed out. A good correlation between rotameric behaviour of the c-5-di(s-tri)diazinyloxymethyl group in the two states is found.     

Visible light induced ‘on water’ benzylic bromination with N-bromosuccinimide

Benzylic bromination of various 4-substituted toluenes (Me, tert-Bu, COOEt and COMe) was effectively conducted with NBS in pure water and with a 40 W incandescent light-bulb as an initiator of the radical chain process, while electron donating groups (OMe and NHAc) directed the reaction to electrophilic aromatic substitution.     

‘Higher-order’ azomethine ylides in the synthesis of functionalized pyrroles and 5-oxo-5H-pyrrolizines

Azafulvenium methides generated by the thermal extrusion of SO₂ from 1-methyl- and 1,1-dimethyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides undergo [1,8]H sigmatropic shifts to give vinylpyrroles. Flash vacuum pyrolysis of the C-vinylpyrroles affords 5-oxo-5H-pyrrolizines or C-allyl-1H-pyrroles.     

‘Push-Pull’ and spirobicyclic structures by reacting N-methyl cyclic ketene-N,X (X=S, O)-acetals with isocyanates and isothiocyanates

Nucleophilic N-methyl cyclic ketene-N,X (X=S, O)-acetals can react with electrophilic aryl isocyanates and aryl isothiocyanates to form ‘push-pull’ mono-adducts, di-adducts and spirobicyclic 6/5 ring compounds.     

Regioselective synthesis of functionalized naphtho[b]thiophenes through a ‘lactone methodology’

Benzo[b]thiophene and its benzannulated derivatives are important classes of compounds due to their unique chemical properties and biosteric relationship with indole. In this letter, we report a convenient route for the synthesis of substituted naphtho[b]thiophenes through a ring transformation reaction of suitably functionalized 2H-pyran-2-ones with 6,7-dihydro-5H-benzothiophene-4-one, in good yields.     

‘O-Acyl isopeptide method’: racemization-free segment condensation in solid phase peptide synthesis

We disclosed a novel ‘racemization-free segment condensation’ based on the ‘O-acyl isopeptide method’ in which an N-segment including C-terminal O-acyl isopeptide structure with urethane-protected Ser/Thr residue was employed for the segment condensation, suggesting that the use of this method contributes to the effective convergent synthesis of long peptides/proteins.     

Synthesis and assignment of the absolute stereochemistry of (+)-hemifistularin 3

The first total synthesis of the marine natural product (+)-hemifistularin 3 in enantiomerically pure form was accomplished by using the amide forming reaction of (+)-spiroisoxazoline ester with the (+)-octopamine derivative. The stereodivergent strategy employed in this effort enabled the assignment of the absolute configurations at the three stereogenic centers in (+)-hemifistularin 3.     

‘Total fluorine’ analysis of seed of Australian Gastrolobium spp. showing temporal, spatial and morphological variation

Alkali-fusion in conjunction with a fluoride selective electrode were used to quantify ‘total fluorine’, being organic fluorine + inorganic fluoride, for the seed of 13 species of Gastrolobium from south-west Western Australia. Intact seed covering spatial and temporal distributions, as well as G. bilobum, G. calycinum and G. parviflorum seed dissected into cotyledons and testa + aril, were analysed. Analysis found significant intra-and inter-species variation, both temporally and spatially, with intact seed concentrations ranging from 1.6 ± 0.3 mg kg⁻¹ in G. spinosum from Mundaring to 1063.9 ± 77.8 mg kg⁻¹ for G. cuneatum from Torbay. Approximately 87% of the ‘total fluorine’ was found to be in the seed cotyledons. Additional analysis detected little inorganic fluoride, indicating the majority of fluorine in the seed is organically bound. Parent compound(s) of the fluorine, seed toxicity and the implications of the results for seed chemical defense are discussed.     

RuO4-promoted oxidative polycyclization of isoprenoid polyenes. A further insight into the stereochemistry of the process

Further studies on the RuO₄-catalyzed oxidative polycyclization of isoprenoid polyenes have been carried out. The configuration of the tris-THF product from the oxidation of geranylgeranyl acetate has been determined by a combination of spectral and chemical correlation methods. The oxidation of (E,Z)-farnesyl acetate, synthesized from nerol, has been carried out. This process stops at the first cyclization indicating that an E configuration of the Δ⁶ double bond is needed for the second cyclization to occur. The results are discussed in comparison with previous knowledge on the related Re(VII) polycyclization of polyenic bis-homoallylic alcohols.     

Dolastanes from the brown alga Dilophus spiralis: absolute stereochemistry and evaluation of cytotoxicity

Five new dolastanes (1-5) were isolated from the brown alga Dilophus spiralis. The structural elucidation of the isolated compounds and the assignment of relative stereochemistry were based on analyses of their spectroscopic data. The structure proposed for 1 was confirmed by single crystal X-ray diffraction analysis, whereas its absolute stereochemistry was determined using the modified Mosher's method. The cytotoxicity of 1-4 was evaluated against seven cell lines.     

The ‘lactone method’: enantioselective preparation of novel P,N-biaryl ligands and their use in the synthesis of the biarylic alkaloids, ancistrotanzanine B and ancistroealaine A

The ‘lactone method’ is a versatile tool for the atroposelective synthesis of axially chiral biaryls. The potential and scope of the concept are highlighted, in particular with respect to its use in the preparation of natural products and chiral auxiliaries. As a new application, the synthesis of novel axially chiral phosphineamines in enantiopure form is described; these ligands were used in the asymmetric Suzuki cross coupling of the molecular portions of the biarylic natural products ancistrotanzanine B and ancistroealaine A.     

Ten new calyxins from Alpinia katsumadai: a systematically studies on the stereochemistry of calyxins

Ten new calyxin natural products, named calyxin N (1), ent-calyxin N (2), calyxin O (3), ent-calyxin O (4), calyxin P (5), 9″-epicalyxin P (6), calyxin Q (7), calyxin R (8), calyxin S (9) and 5-epicalyxin S (10), were isolated from the seeds of Alpinia katsumadai. Their planar structures were elucidated by a combination of various spectroscopic methods, primarily NMR and MS, while the absolute configurations of the isolated calyxins were comprehensively studied by the modified Mosher's method, electronic circular dichroism (ECD) and theoretical calculations. This is the first systematically study on the absolute configurations of calyxins. Most of the isolated compounds showed moderate to strong antiproliferative activities against NCI-H460, HeLa, SMMC-7721 and HCT-116 cancer cell lines.     

Donnazoles A and B from Axinella donnani sponge: very close derivatives from the postulated intermediate ‘pre-axinellamine’

Two novel dimeric pyrrole-aminoimidazole (PAI) alkaloids (−) donnazoles A-B (1-2) were isolated from the marine sponge Axinella donnani collected off the Mauritius Island. Their structures were elucidated mainly by 2D NMR. Both compounds bear the crucial substituted cyclopentane of ‘pre-axinellamine’, the hypothetical common intermediate of all dimeric PAIs. Additionally, the essential trans-6,7 ring junction of palau′amine’s congeners is already established in 1 and 2. The absolute configurations of 1 and 2 were deduced via NOE correlations in combination with the comparison of their circular dichroism data with the one of (−) sceptrin. The absolute configuration of (−) donnazoles A (1) and B (2) is coherent with the absolute configuration of the known dimeric members of PAI alkaloids.     

‘Click’ to bidentate bis-triazolyl sugar derivatives with promising biological and optical features

Bidentate 1-O-methyl-α-d-pyranoglucosides bearing two triazolyl α-ketoester groups on the 2,6- or 3,4-positions of sugar scaffold were efficiently synthesized via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (click reaction) in good yields. These newly featured sugar derivatives displayed favorable inhibitory activity on protein tyrosine phosphatase 1B (PTP1B) and unexpected selective fluorescence quenching in the presence of Ni²⁺.     

The first total synthesis and absolute stereochemistry of plakortone G from the Jamaican sponge Plakortis sp.

Total synthesis of plakortone G (1), a secondary metabolite of the Jamaican sponge Plakortis sp., was successfully achieved. The absolute configuration of this molecule was determined by comparison of the synthetic diastereomers with reported data to possess the (4R,8R)-configuration 14.     

Highly efficient one-pot, three-component Mannich reaction catalysed by boric acid and glycerol in water with major ‘syn’ diastereoselectivity

Boric acid and glycerol efficiently catalysed the one-pot, three-component Mannich reaction of aldehydes, aromatic amines and cyclic ketones in water at ambient temperature to afford the corresponding β-amino carbonyl compounds in good yields. All but one reaction proceeded with moderate ‘syn’ diastereoselectivity. This observation is just the reverse of the major anti diastereoselectivity obtained in most of the earlier reported procedures. The methodology is mild and efficient using minute quantities of catalyst with no side products and a very simple work-up procedure.