Determination of the Absolute Configuration of Quercivorol, (1S,4R)-p-Menth-2-en-1-ol,an Aggregation Pheromone of the Ambrosia Beetle Platypus quercivorus (Coleoptera: Platypodidae)

A pair of enantiomers of trans-p-menth-2-en-1-ol, an aggregation pheromone of Platypus quercivorus, was synthesized from (S)- and (R)-limonene. The retention time of the aggregation pheromone from the insect coincided with that of (1S,4R)-p-menth-2-en-1-ol synthesized from (S)-limonene from GC analyses with a chiral column, enabling the absolute configuration of the aggregation pheromone to be determined as (1S,4R).     

Discovery and characterization of chemical signals for citrus root weevil, Diaprepes abbreviatus

The tropical root weevil Diaprepes abbreviatus (L. 1758) (Coleoptera: Curculionidae) is a polyphagous insect from the Caribbean Islands and an invasive insect in the southern part of the United States where it is pest of citrus crops and ornamental trees. Adults feed upon foliage where aggregation, mating and oviposition take place. Here, the headspace volatiles from Citrus macrophylla Wester (Rutaceae), D. abbreviatus adults feeding on this plant, adults alone and adult feces, were collected by aeration and solid-phase microextraction (SPME) for analysis by gas chromatography-linked mass spectrometry (GC-MS). Electrophysiological responses of weevil antennal receptors to volatile headspace extracts and synthetic analogues were recorded by gas chromatography-linked electroantennographic detection (GC-EAD) and electroantennograms (EAGs). Antennal responses were recorded to the monoterpenes (R)-(−)-linalool, citronellal, nerol, citral, and geraniol; all present in the headspace of C. macrophylla. Antennal responses were also recorded to carvacrol, present in the headspace of adults and adult feces. The green leaf volatiles cis-3-hexen-1-ol and trans-2-hexen-1-ol, produced by other host plants, elicited reliable responses on the D. abbreviatus antenna. When comparing EAGs between (±)-linalool and (R)-(−)-linalool, no significant difference was found; responses to (R)-(+)-citronellal were larger than for (S)-(−)-citronellal. Among the individual compounds and blends tested using an open T-track dual choice olfactometer, only the blend of (±)-linalool, cis-3-hexen-1-ol and carvacrol (source dose 25:25:2.5 μg) elicited significant attraction of females, the same blend was repellent for males. The biologically active compounds found here likely play a role in host finding by D. abbreviatus and other interactions of the insect with its hostplant. Handling editor: Sam Cook     

Chirality and biosynthesis of lilac compounds in Actinidia arguta flowers

Biosynthesis of lilac compounds in ‘Hortgem Tahi’ kiwifruit (Actinidia arguta) flowers was investigated by treating inflorescences with d₅-linalool. The incorporation of the deuterium label into 8-hydroxylinalool, 8-oxolinalool, the lilac aldehydes, alcohols, and alcohol epoxides was followed by GC-MS and enantioselective GC-MS. Both (R)- and (S)-linalool were produced naturally by the flowers, but 8-hydroxylinalool, 8-oxolinalool, and the lilac aldehydes and alcohols occurred predominantly as the (S) and 5′(S)-diastereoisomers, respectively. The enantioselective step in the biosynthesis of the lilac aldehydes and alcohols was concluded to be the oxidation of linalool to (S)-8-hydroxylinalool. In contrast, the lilac alcohol epoxides had a 5′(R):(S) ratio, the same as for linalool, which suggests that either these compounds are not synthesised from the 5′(S)-configured lilac aldehydes and alcohols, or that if indeed they are, then it is by an enantioselective step that favours utilisation of the 5′(R)-configured compounds.     

Lipase-Catalyzed Kinetic Resolution of (±)-cis-Flavan-4-ol and Its Acetate: Synthesis of Chiral 3-Hydroxyflavanones

Lipase-catalyzed kinetic resolution of (±)-cis-flavan-4-ol and its acetate led to enantiomerically enriched flavan-4-ol and its acetate. These chiral compounds were converted to (2R, 3R)- and (2S, 3S)-3-hydroxyflavanones.     

Synthesis of (+)-Juvabione,a Compound with Juvenile Hormone Activity

(+)-Juvabione 1 was synthesized by employing (1R,4S,6S)-6-hydroxybicyclo[2.2.2]octan-2-one 2 as a chiral source.

(+)-Juvabione 1 shows juvenile hormone activity, and its racemate has been repeatedly synthesized.¹⁾ Optically active 1 was synthesized by Pawson et al. from (+)-limonene, ²⁾ and by Trost et al. from (+)-perillaldehyde.³⁾ However, their syntheses were not at all efficient for providing a suitable amount of optically active 1.     

Biosynthesis and enantioselectivity in the production of the lilac compounds in Actinidia arguta flowers

Biosynthesis of the lilac alcohols and alcohol epoxides from linalool in ‘Hortgem Tahi’ kiwifruit (Actinidiaarguta) flowers was investigated by incubating flowers with rac-linalool, rac-[4,4,10,10,10-²H₅]linalool, (R)-8-hydroxylinalool and (R)-8-oxolinalool. All substrates were incorporated into the lilac alcohols although the (R)-configured compounds are not normally present in flowers. Biosynthesis of the lilac alcohol epoxides from rac-1,2-epoxy[4,4,10,10,10-²H₅]linalool and rac-[4′,4′, 8′, 8′,8′-²H₅]lilac aldehyde epoxide, rather than the lilac alcohols, was examined. Both substrates were non-enantioselectively converted to the lilac alcohol epoxides, suggesting two biosynthetic pathways for these compounds, contrary to previous reports. Their ability to process unnatural substrates indicates that A.arguta flowers have a greater biosynthetic capability than is suggested by their phytochemical composition. Linalool, the lilac compounds, and their biosynthetic intermediates were measured in the pistils, stamen, petals and sepals to determine if localisation in different organs contributed to only (S)-linalool being processed to the lilac compounds. Both linalool enantiomers were present in all organs, while most (97%) of the lilac compounds, and their precursors, were found in the petals. (S)-Linalool was not depleted from the flower petals, with respect to (R)-linalool, during the time of maximum production of the metabolites of (S)-linalool.     

Synthesis and in vitro sodium channel blocking activity evaluation of novel homochiral mexiletine analogs

New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use‐dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated that all of them exerted a higher use‐dependent block than mexiletine. The most potent analog, (S)‐3‐(2,6‐dimethylphenoxy)‐1‐phenylpropan‐1‐amine (S)‐( 5 ), was six‐fold more potent than (R)‐Mex in producing a tonic block. As observed with mexiletine, the newly synthesized compounds exhibit modest enantioselective behavior, that is more evident in 3‐(2,6‐dimethylphenoxy)butan‐1‐amine ( 3 ). Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Occurrence of Taurine-Pyruvate Aminotransferase in Bacterial Extract

Natural ( + )-(1R,2S,3S)-methyl cucurbate (1b) and the ( – )-δ-lactone of 3-epi-cucurbic acid (16) were synthesized from (+)-(1R,6S,7R)-bicyclo [4.3.0] non-3-en-7-ol (5). Asymmetric hydrolysis of the acetate (8) of ( ± )-5 with pancreatin gave optically pure the ( + )-(7R)-alcohol (5) and (–)-(7S)-acetate (8). An ozonolysis product of ( + )-5 was transformed to ( – )-16 and ( + )-(3S)-1b with inversion of the (7R)-hydroxyl group. Similarly, unnatural (–)-1b and (+)-16 were prepared from optically pure ( — )-5. The growth inhibitory activities of these synthesized chiral compounds toward lettuce seedlings were examined.     

Enantioseparation of mandelic acid on vancomycin column: Experimental and docking study

So far, no detailed view has been expressed regarding the interactions between vancomycin and racemic compounds including mandelic acid. In the current study, a chiral stationary phase was prepared by using 3-aminopropyltriethoxysilane and succinic anhydride to graft carboxylated silica microspheres and subsequently by activating the carboxylic acid group for vancomycin immobilization. Characterization by elemental analysis, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, and thermogravimetric analysis demonstrated effective functionalization of the silica surface. R and S enantiomers of mandelic acid were separated by the synthetic vancomycin column. Finally, the interaction between vancomycin and R/S mandelic acid enantiomers was simulated by Auto-dock Vina. The binding energies of interactions between R and S enantiomers and vancomycin chiral stationary phase were different. In the most probable interaction, the difference in mandelic acid binding energy was approximately 0.2 kcal/mol. In addition, circular dichroism spectra of vancomycin interacting with R and S enantiomers showed different patterns. Therefore, R and S mandelic acid enantiomers may occupy various binding pockets and interact with different vancomycin functions. These observations emphasized the different retention of R and S mandelic acid enantiomers in vancomycin chiral column.     

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

Enantiopure 3‐((R)‐ and 3‐((S)‐1‐phenylethyl)‐4‐oxazoline‐2‐ones were evaluated as chiral building blocks for the divergent construction of heterocycles with stereogenic quaternary centers. The N‐(R)‐ or N‐(S)‐1‐phenylethyl group of these compounds proved to be an efficient chiral auxiliary for the asymmetric induction of the 4‐ and 5‐positions of the 4‐oxazolin‐2‐one ring through thermal and MW‐promoted nucleophilic conjugated addition to Michael acceptors and alkyl halides. The resulting adducts were transformed via a cascade process into fused six‐membered carbo‐ and heterocycles. The structure of the reaction products depended on the electrophiles and reaction conditions used. Alternative isomeric 4‐methylene‐2‐oxazolidinones served as chiral precursors for a versatile and divergent approach to highly substituted cyclic carbamates. DFT quantum calculations showed that the formation of bicyclic pyranyl compounds was generated by a diastereoselective concerted hetero‐Diels‐Alder cycloaddition.     

Coleifolides A and B,Two New Sesterterpenoids from the Aerial Parts of Scutellaria coleifolia H.Lév.

Coleifolides A and B ( 1 and 2 ), two new sesterterpenoids with a β‐methyl‐α,β‐unsaturated‐γ‐lactone moiety, were isolated from the aerial parts of Scutellaria coleifolia H.Lév . (Lamiaceae), together with three known compounds. Their structures were elucidated by NMR and MS examinations. Coleifolides A and B were concluded to be partially racemic compounds by the HPLC analysis using a chiral column or introduction of chiral derivatizing agents. The absolute configuration of the major isomer was determined by analyses of the CD spectrum as well as NMR data of (R)‐ and (S)‐2‐NMA derivatives. Coleifolides A and B are structurally similar to manoalide derivatives, previously isolated from marine sponges, and appear to be the first examples of this type of compounds being isolated from higher plants.     

Synthesis of enantiopure planar chiral bis‐(para)‐pseudo‐meta‐type [2.2]paracyclophanes

A new type of planar chiral (R_p)‐ and (S_p)‐4,7,12,15‐tetrasubstituted [2.2]paracyclophanes was prepared from racemic 4,7,12,15‐tetrabromo[2.2]paracyclophane as the starting substrate. Regioselective lithiation and transformations afforded racemic bis‐(para)‐pseudo‐meta‐type [2.2]paracyclophane (4,15‐dibromo‐7,12‐dihydroxy[2.2]paracyclophane). Its optical resolution was performed by the diastereomer method using a chiral camphanoyl group as the chiral auxiliary. The diastereoisomers were readily isolated by simple silica gel column chromatography, and the successive hydrolysis afforded (R_p)‐ and (S_p)‐bis‐(para)‐pseudo‐meta‐type [2.2]paracyclophanes ((R_p)‐ and (S_p)‐4,15‐dibromo‐7,12‐dihydroxy[2.2]paracyclophanes). They can be used as pseudo‐meta‐substituted chiral building blocks.     

Transformation of menthane monoterpenes by Mentha piperita cell culture

(+)-Isopiperitenone (100 mg l^–1) was converted into (4S,6R)-6-hydroxy- and (4S,8R)-8,9-epoxyisopiperitenone, aside from the already known (+)-7-hydroxyisopiperitenone, by suspension cell culture of Mentha piperita. As (–)-isopiperitenone was hydroxylated similarly, this implies that the hydroxylating enzyme(s) have a broad substrate stereospecificity in regards to the stereochemistry at C4. (–)-(4R)-Carvone was reduced by the Mentha cells both at carbonyl and C1-C6 double bond to give (1R,2S,4R)-neodihydrocarveol and (1R,2R,4R)-dihydrocarveol with the former being the major product. (+)-(4S)-Carvone had a similar reduction pattern, producing (1S,2R,4S)-neodihydrocarveol and (1S,4S)-dihydrocarvone. Formation of these compounds indicates that the peppermint cell culture cannot only hydroxylate the allylic position but also reduce the ,-unsaturated carbonyl system.     

The novel inhibitors of serine proteases

Thirty optically active nonprotein α-amino acids and peptides based thereon have been screened for their ability to interact with bovine trypsin and proteinase K from Tritirachium album Limber, which belong to the group of serine proteases. Both structure-based drug design approach and determination of enzyme activity have been used to identify low molecular weight inhibitors of trypsin and proteinase K. Compounds have been selected that according to the docking analysis were able to interact with trypsin and proteinase K. Following the docking analysis measurement of enzymes activity (2R,3S)-β-hydroxyleucine and (2S,3R)-β-hydroxyleucine inhibited both enzymes activity, whereas (S)-α-methyl-β-phenylalanine, (R)-α-methyl-β-phenylalanine, (S)-allylglycine, (R)-allylglycine, (S)-α-allylalanine, (R)-α-allylalanine and allo-O-ethylthreonine inhibited only proteinase K; and N-formyl-(S)-methionyl-(2S,3R)-hydroxyleucine, N-formyl-(S)-methionyl-(2R,3S)-hydroxyleucine, N-formyl-(S)-methionyl-(S)-allylglycine and N-formyl-(S)-methionyl-(R)-allylglycine inhibited trypsin. It has been shown that inhibition of trypsin by (2R,3S)-β-hydroxyleucine and N-formyl-(S)-methionyl-(2R,3S)-hydroxyleucine is of a competitive mode.     

Synthesis,chromatographic resolution and chiroptical properties of carboxyibuprofen stereoisomers: Major metabolites of ibuprofen in man

The chromatographic resolution of the four stereoisomers of carboxyibuprofen, a major metabolite of ibuprofen in man, was achieved using a Chiralpak AD chiral stationary phase (CSP) (J.T. Baker, Milton, Keynes, UK). The elution order of the stereoisomers was determined to be 2′S,2R; 2′R,2R; 2′R,2S; 2′S,2S by a combination of stereoselective synthesis of diastereoisomeric mixtures and analysis of the two diastereoisomers isolated from human urine following the administration of (S)-ibuprofen. The individual stereoisomers were isolated by semipreparative chiral phase chromatography and characterized by circular dichroism spectroscopy. Chirality 9:75–87, 1997. © 1997 Wiley-Liss, Inc.     

Absolute Configuration of Hydroxycitric Acid Produced by Microorganisms

Optical resolution for (2S,3R) and (2R,3S)-hydroxycitric acid (HCA) enantiomers was developed using chiral column chromatography. HCA from Bacillus megaterium G45C and Streptomyces sp. U121, newly isolated in our previous study, was analyzed to determine the absolute configuration. These results indicate that both strains generate optically pure (2S,3R)-hibiscus type HCA enantiomer.     

Preparation of Optically Active 2-Aminobutanoic Acid via Optical Resolution by Replacing Crystallization

An attempt was made to use a simple procedure to obtain (R)- and (S)-2-aminobutanoic acids [(R)- and (S)-1] which are non-proteinogenic α-amino acids and are useful as chiral reagents in asymmetric syntheses. Compound (RS)-1 p-toluenesulfonate [(RS)-2], which is known to exist as a conglomerate, was optically resolved by replacing crystallization with (R)- and (S)-methionine p-toluenesulfonate [(R)- and (S)-3] as optically active co-solutes. When (S)-3 was employed as the co-solute, (R)-2 was preferentially crystallized from a supersaturated solution of (RS)-2 in 1-propanol, as was (S)-2 in the presence of (R)-3. (R)- and (S)-2 recrystallized from 1-propanol were treated with triethylamine in methanol to give (R)- and (S)-1 in optically pure forms.     

Absolute configurations and CD spectra of axially chiral biphenyls prepared in a facile manner by crystallization‐induced configuration transformation

Axially chiral biphenyls such as (M,S)‐ 3k have been conveniently obtained by crystallization of their diastereomeric mixtures, which were synthesized from racemic 4,4′‐dimethoxy‐5,6,5′,6′‐bis(methylenedioxy)‐2‐carboxylester‐2′‐carboxyl‐biphenyls 4 and chiral amino alcohols (R)‐alaninol, (S)‐alaninol, (S)‐valinol, and (S)‐phenylalaninol. A crystallization‐induced configuration transformation of the biphenyls was thus achieved. It was found that amide formation of an (S)‐valinol or (S)‐phenylalaninol at the 2′‐position of the biphenyl usually induced the deposition of crystals with the (M)‐configuration from ethanol in yields higher than 50%. The absolute configurations (ACs) of two crystalline biphenyls have been determined by X‐ray crystallographic analysis. The ACs of nine biphenyls have been assigned based on their CD spectra. Further, stability investigation of these axially chiral biphenyls revealed that the ACs could revert upon redissolution. The energy barrier to epimerization between (P,R)‐ 3b and (M,R)‐ 3b was measured as ΔG^# = 21.45 kcal/mol and the half‐life in ethanol at 301 K was 17.1 h. Chirality, 2010. © 2010 Wiley‐Liss, Inc.