Steric Considerations on Improving the Diastereomeric Ratio of (+)‐ and (−)‐Neomenthyl Phenyl Sulfoxides Using Bulky‐Headed Oxidant Hexadecyltrimethylammonium Periodate and Assignment of Their Configuration

The bulky‐headed oxidant hexadecyltrimethylammonium periodate affords the diastereomeric pairs, (Ss)‐(+)/(Rs)‐(+) and (Ss)‐(?)/(Rs)‐(?)‐neomenthyl phenyl sulfoxides in stereochemically pure states with improved diastereomeric excess (48% diastereomeric excess [de]) as compared to its nonbulky counterpart, sodium metaperiodate (28% de) from respective (+)/(?)‐neomenthyl phenyl sulfides. Steric effects involving the head group volume of hexadecyltrimethylammonium periodate is found to play a role in improving the diastereomeric ratio of the products. The two diastereomers can be readily separated by column chromatography. Absolute configuration at the sulfur center in (+)‐neomenthyl phenyl sulfoxide was determined by single‐crystal X‐ray crystallography and found to be Ss. Relative configurations of other sulfoxides were assigned based on the configuration of (+)‐neomenthyl phenyl sulfoxide. Chirality 27:370–374, 2015. © 2015 Wiley Periodicals, Inc.     

Chiral Pool‐Based Synthesis of Naphtho‐Fused Isocoumarins

A variety of chiral derivatives of benzo[d]naphtho[1,2‐b]pyran‐6‐one were prepared in a single step by Et₃N‐mediated condensation of homophthalic anhydride with different derivatives of (S)‐amino acid chlorides at –5 °C by employing a chiral pool methodology. Chirality 27:951–957, 2015. © 2015 Wiley Periodicals, Inc.     

Application of NMR spectroscopy for assignment of the absolute configuration of 8‐tert‐butyl‐2‐hydroxy‐7‐methoxy‐8‐methyl‐9‐oxa‐6‐azaspiro[4.5]dec‐6‐en‐10‐one

In order to assign the absolute configurations of 8‐tert‐butyl‐2‐hydroxy‐7‐methoxy‐8‐methyl‐9‐oxa‐6‐azaspiro[4.5]dec‐6‐en‐10‐one ( 2a , 2b ), their esters ( 5a , 5b , 5c , 5d ) with (R)‐ or (S)‐2‐methoxyphenylacetic acid ( 4a , 4b ) have been synthesized. The absolute configurations of these compounds have been determined on the basis of NOESY correlations between the protons of the tert‐butyl group and the cyclopentane fragment of the molecules. The crucial part of this analysis was assignment of the absolute configuration at C‐5. Additionally, by calculation of the chemical shift anisotropy, δ^RS, for the relevant protons, it was also possible to confirm the absolute configurations at the C‐2 centres of compounds 2a , 2b and 5a , 5b , 5c , 5d . Chirality, 25:422–426, 2013.© 2013 Wiley Periodicals, Inc.     

Unexpected Loss of Stereoselectivity in Ring‐Opening Reaction of 2‐Alkoxy‐2‐Thio‐1,3,2‐Oxathiaphospholanes With a Pyrophosphate Anion

A reaction of DBU promoted ring opening in nucleoside‐3'‐O‐ and nucleoside‐5'‐O‐(2‐thio‐4,4‐pentamethylene‐1,3,2‐oxathiaphospholane) monomers with a pyrophosphate or a methylenediphosphonate anion proceeds with substantial loss of stereoselectivity. Depending on the absolute configuration of the phosphorus atom, so far widely accepted the stereoretentive mechanism of condensation is accompanied by a stereoinvertive one, most likely employing an intramolecular ligand–ligand exchange in an uncharged intermediate. Chirality 27:155–122, 2015. © 2014 Wiley Periodicals, Inc     

Stereoselective Synthesis of (R)‐3‐Methylthalidomide by Piperidin‐2‐one Ring Assembly Approach

A simple and stereoselective synthesis of 3‐methylthalidomide, a configurationally stable thalidomide analog, is presented. Herein we describe the synthesis of (R)‐3‐methylthalidomide starting from (S)‐alanine by piperidin‐2‐one ring assembly approach in high yield and enantiomeric purity without using a chiral auxiliary or reagent. Starting from (R)‐alanine, the corresponding (S)‐3‐methylthalidomide can be prepared using the same methodology. Chirality 27:619–624, 2015. © 2015 Wiley Periodicals, Inc.     

Field evaluation on the synergistic attractiveness of 2‐(1‐undecyloxy)‐1‐ethanol and ipsenol to Monochamus saltuarius

To develop an optimal attractant for Monochamus saltuarius (Gebler) (Coleoptera: Cerambycidae), the synergistic effects of a few potential attractants (ethanol and α‐pinene as host‐plant volatiles, and ipsenol and ipsdienol as bark beetle pheromones) were tested in a pine forest combined with 2‐(1‐undecyloxy)‐1‐ethanol (monochamol), the aggregation pheromone of Monochamus species, for two consecutive years, 2014 and 2015. Total number of catches was 65 and 33 in 2014 and 2015, respectively. Ethanol or ethanol + monochamol (a base blend) were not attractive to M. saltuarius with no difference from the control. Addition of α‐pinene and ipsdienol to the base blend did not significantly increase catches. However, ipsenol was significantly synergistic to the base blend in attracting M. saltuarius in 2014, and the blend (ipsenol + base blend) attracted meaningfully higher numbers of M. saltuarius in 2015. Our study illustrates the potential for monochamol and ipsenol baits for monitoring and trapping of M. saltuarius in the field.     

Planar Chiral Iridium Complexes with the Δ‐TRISPHAT Anion: Toward the First Enantiopure o‐Quinone Methide π‐Complex

We describe the resolution of a planar chiral cationic iridium complex [Cp*Ir(η⁵‐2‐methyl‐oxodienyl)][OT f] ( 2 ) following the counterion strategy, where anion metathesis by Δ‐TRISPHAT generates the two diastereomers (pR, pS)‐[Cp*Ir(η⁵‐2‐methyl‐oxodienyl)][Δ‐TRISPHAT] ( 3a , 3a' ). Upon fractional crystallization both compounds were separated as confirmed by ¹H nuclear magnetic resonance (NMR) and circular dichroism studies recorded in solution. The latter represents the key‐complex precursors for the enantioselective synthesis of metallated o‐quinone methide complexes ( 4a , 4a' ). Chirality 25:449–454, 2013. © 2013 Wiley Periodicals, Inc.     

Theoretical and Molecular Docking Study of Ketoconazole on Heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin as Chiral Selector

A molecular docking study, using molecular mechanics calculations with AutoDock and semi‐empirical PM3 calculations, was used to predict the enantiodiscrimination of heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin (TMβCD) and ketoconazole (KTZ) enantiomers. A Density Functional Theory (DFT) single‐point calculation at the level of B3LYP/6‐311G (d,p) was performed for the PM3‐optimized complexes to obtain more accurate binding energy and the electronic structures of the complexes. The difference in energies of the inclusion complexes between the KTZ enantiomers and TMβCD is probably a measure of chiral discrimination, which results in the separation of the enantiomers as observed in the experimental studies. Chirality 28:209–214, 2016. © 2015 Wiley Periodicals, Inc.     

Thermoluminescence and photoluminescence studies on γ‐ray‐irradiated Ce3+,Tb3+‐doped potassium chloride single crystals

Single crystals of KCl doped with Ce³⁺,Tb³⁺ were grown using the Bridgeman–Stockbarger technique. Thermoluminescence (TL), optical absorption, photoluminescence (PL), photo‐stimulated luminescence (PSL), and thermal‐stimulated luminescence (TSL) properties were studied after γ‐ray irradiation at room temperature. The glow curve of the γ‐ray‐irradiated crystal exhibits three peaks at 420, 470 and 525 K. F‐Light bleaching (560 nm) leads to a drastic change in the TL glow curve. The optical absorption measurements indicate that F‐ and V‐centres are formed in the crystal during γ‐ray irradiation. It was attempted to incorporate a broad band of cerium activator into the narrow band of terbium in the KCl host without a reduction in the emission intensity. Cerium co‐doped KCl:Tb crystals showed broad band emission due to the d–f transition of cerium and a reduction in the intensity of the emission peak due to ⁵D₃–⁷F_j (j = 3, 4) transition of terbium, when excited at 330 nm. These results support that energy transfer occurs from cerium to terbium in the KCl host. Co‐doping Ce³⁺ ions greatly intensified the excitation peak at 339 nm for the emission at 400 nm of Tb³⁺. The emission due to Tb³⁺ ions was confirmed by PSL and TSL spectra. Copyright © 2015 John Wiley & Sons, Ltd.     

Preparative Enantioseparation of (RS)‐Baclofen: Determination of Molecular Dissymmetry

The present work reports preparative enantioseparation of (RS)‐baclofen using thin‐layer chromatography (TLC) and high‐performance liquid chromatography (HPLC). Diastereomers were synthesized using a new monochloro‐s‐triazine‐based chiral derivatizing reagent (CDR), namely, N‐(4‐chloro‐6‐piperidinyl‐[1,3,5]‐triazine‐2‐yl)‐L‐phenylalanine, under microwave irradiation. Acetonitrile‐0.1% aq. triflouroacetic acid in gradient elution mode and CH₃OH‐CH₂Cl₂ (4:5; v/v) were successful as mobile phase in HPLC and TLC, respectively. The two diastereomers were isolated by preparative TLC. Molecular dissymmetry was established by developing the lowest energy optimized structures of the diastereomers based on Density Functional Theory and with the help of ¹H NMR showing anisotropic effect associated with aromatic ring of s‐triazine (in the CDR). The configuration of diastereomers was established as [L‐Phe‐(R)‐Bac] and [L‐Phe‐(S)‐Bac], where the first notation refers to the configuration of chiral auxiliary (of the CDR) and the second to that of the analyte Bac. Limits of detection were found to be 0.056 and 0.061 ng mL^?1, respectively, for the two diastereomers. Determination of absolute configuration of the two diastereomers lent support to the elution order and separation mechanism.Chirality 27:299–305, 2015. © 2015 Wiley Periodicals, Inc.     

Asymmetric Borane Reduction of Prochiral Ketones Catalyzed By Helical Poly[(S)‐3‐vinyl‐2,2'‐dihydroxy‐1,1'‐binaphthyl]

The application of helical poly[(S)‐3‐vinyl‐2,2'‐dihydroxy‐1, 1'‐binaphthyl] ( L* ) in the asymmetric borane reduction of prochiral ketones was studied. The results showed that L* had excellent catalytic activity as well as enantioselectivity, giving up to 96% yield and up to 99% enantiomeric excess (ee) of the corresponding secondary alcohol at 25 °C. Moreover, L* can be easily recovered and reused without loss of catalytic activity. Chirality 27:422–424, 2015. © 2015 Wiley Periodicals, Inc.     

Diverse modes of 5′‐[4‐(aminoiminomethyl)phenyl]‐[2,2′‐bifuran]‐5‐carboximidamide (DB832) interaction with multi‐stranded DNA structures

The modes of binding of 5′‐[4‐(aminoiminomethyl)phenyl]‐[2,2′‐Bifuran]‐5‐carboximidamide (DB832) to multi‐stranded DNAs: human telomere quadruplex, monomolecular R‐triplex, pyr/pur/pyr triplex consisting of 12 T*(T·A) triplets, and DNA double helical hairpin were studied. The optical adsorption of the ligand was used for monitoring the binding and for determination of the association constants and the numbers of binding sites. CD spectra of DB832 complexes with the oligonucleotides and the data on the energy transfer from DNA bases to the bound DB832 assisted in elucidating the binding modes. The affinity of DB832 to the studied multi‐stranded DNAs was found to be greater (K_ass ≈ 10⁷M^?1) than to the duplex DNA (K_ass ≈ 2 × 10⁵M^?1). A considerable stabilizing effect of DB832 binding on R‐triplex conformation was detected. The nature of the ligand tight binding differed for the studied multi‐stranded DNA depending on their specific conformational features: recombination‐type R‐triplex demonstrated the highest affinity for DB832 groove binding, while pyr/pur/pyr TTA triplex favored DB832 intercalation at the end stacking contacts and the human telomere quadruplex d[AG₃(T₂AG₃)₃] accommodated the ligand in a capping mode. Additionally, the pyr/pur/pyr TTA triplex and d[AG₃(T₂AG₃)₃] quadruplex bound DB832 into their grooves, though with a markedly lesser affinity. DB832 may be useful for discrimination of the multi‐sranded DNA conformations and for R‐triplex stabilization. © 2009 Wiley Periodicals, Inc. Biopolymers 93: 8–20, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com     

N‐[2‐[(3‐Chlorophenyl)amino]‐phenyl]‐3‐(difluoromethyl)‐1‐methyl‐1H‐pyrazole‐4‐carboxamide: Synthesis,Crystal Structure,Molecular Docking and Biological Activities

In continuation of our previous research on the development of novel pyrazole‐4‐carboxamide with potential antifungal activity, compound SCU2028 , namely N‐[2‐[(3‐chlorophenyl)amino]phenyl]‐3‐(difluoromethyl)‐1‐methyl‐1H‐pyrazole‐4‐carboxamide, was synthesized by new method, structurally characterized by IR, HR‐ESI‐MS, ¹H‐ and ¹³C‐NMR spectra and further identified by single‐crystal X‐ray diffraction. In pot tests, compound SCU2028 showed good in vivo antifungal activity against Rhizoctonia solani (R. solani) and IC₅₀ value of it was 7.48 mg L^?1. In field trials, control efficacy of compound SCU2028 at 200 g.a.i. ha^?1 was 42.30 % on the 7^th day after the first spraying and 68.10 % on the 14^th day after the second spraying, only slightly lower than that of thifluzamide (57.20 % and 71.40 %, respectively). Further in vitro inhibitory activity showed inhibitory ability of compound SCU2028 was 45‐fold higher than that of bixafen and molecular docking of compound SCU2028 to SDH predicted its binding orientation in the active site of the target protein SDH. These results suggested that compound SCU2028 was a potential fungicide for control of rice sheath blight.     

Synthesis and Biological Activity of New 4‐tert‐Butylcyclohexanone Derivatives

In the synthesis performed in this study, derivatives of 4‐tert‐butylcyclohexanone 1 were obtained using typical reactions of organic synthesis. The bioactivity of the selected compounds was evaluated. 1‐(Bromomethyl)‐8‐tert‐butyl‐2‐oxaspiro[4.5]decan‐3‐one ( 5 ) was characterized by attractant properties against larvae and a weak feeding deterrent activity against adults of Alphitobius diaperinus Panzer . This bromolactone was a moderate antifeedant towards Myzus persicae Sulzer . In addition, ethyl (4‐tert‐butylcyclohexylidene)acetate ( 2 ) and bromolactone 5 displayed antibacterial activity. The strongest bacteriostatic effect was observed against Gram‐positive strains: Bacillus subtilis and Staphylococcus aureus. The bromolactone 5 also limited the growth of Escherichia coli strain.     

Resolution of 1‐n‐Butyl‐3‐Methyl‐3‐Phospholene 1‐Oxide With TADDOL Derivatives and Calcium Salts of O,O'‐Dibenzoyl‐(2R,3R)‐ or O,O'‐di‐p‐Toluoyl‐(2R,3R)‐tartaric Acid

The resolution methods applying (?)‐(4R,5R)‐4,5‐bis(diphenylhydroxymethyl)‐2,2‐dimethyldioxolane (“TADDOL”), (?)‐(2R,3R)‐α,α,α',α'‐tetraphenyl‐1,4‐dioxaspiro[4.5]decan‐2,3‐dimethanol (“spiro‐TADDOL”), as well as the acidic and neutral Ca²⁺ salts of (?)‐O,O'‐dibenzoyl‐ and (?)‐O,O'‐di‐p‐toluoyl‐(2R,3R)‐tartaric acid were extended for the preparation of 1‐n‐butyl‐3‐methyl‐3‐phospholene 1‐oxide in optically active form. In one case, the intermediate diastereomeric complex could be identified by single‐crystal X‐ray analysis. The absolute P‐configuration of the enantiomers of the phospholene oxide was also determined by comparing the experimentally obtained and calculated CD spectra. Chirality 26:174–182, 2014. © 2014 Wiley Periodicals, Inc.     

Copper‐Chiral Camphor β‐Amino Alcohol Complex Catalyzed Asymmetric Henry Reaction

Four novel chiral amino alcohols were synthesized from D‐(+)‐camphor and utilized as ligands in a Cu(I)‐catalyzed asymmetric Henry reaction. The reactions were carried out under mild conditions with excellent enantioselectivities and moderate yields without the exclusion of air or moisture. The highest enantioselectivity was observed up to 94% enantiomeric excess (ee) with ligand L1 in toluene at room temperature. Chirality 27:761–765, 2015. © 2015 Wiley Periodicals, Inc.     

Antiproliferative Evaluation of Some 2‐[2‐(2‐Phenylethenyl)‐cyclopent‐3‐en‐1‐yl]‐1,3‐benzothiazoles: DFT and Molecular Docking Study

The 2‐[2‐(2‐phenylethenyl)cyclopent‐3‐en‐1‐yl]‐1,3‐benzothiazoles were synthesized from the reactions of 7‐benzylidenebicyclo[3.2.0]hept‐2‐en‐6‐ones with 2‐aminobenzenethiol. The antiproliferative activities of 2‐[2‐(2‐phenylethenyl)cyclopent‐3‐en‐1‐yl]‐1,3‐benzothiazoles were determined against C6 (rat brain tumor) and HeLa (human cervical carcinoma cells) cell lines using BrdU cell proliferation ELISA assay. Cisplatin and 5‐fluorouracil (5‐FU) were used as standards. The most active compound was 2‐{(1S,2S)‐2‐[(E)‐2‐(4‐methylphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole against C6 cell lines with IC₅₀=5.89 μm value (cisplatin, IC₅₀=14.46 μm and 5‐FU, IC₅₀=76.74 μm ). Furthermore, the most active compound was 2‐{(1S,2S)‐2‐[(E)‐2‐(2‐methoxyphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole against HeLa cell lines with IC₅₀=3.98 μm (cisplatin, IC₅₀=37.95 μm and 5‐FU, IC₅₀=46.32 μm ). Additionally, computational studies of related molecules were performed by using B3LYP/6‐31G+(d,p) level in the gas phase. Experimental IR and NMR data were compared with the calculated results and were found to be compatible with each other. Molecular electrostatic potential (MEP) maps of the most active 2‐{(1S,2S)‐2‐[(E)‐2‐(2‐methoxyphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole against HeLa and the most active 2‐{(1S,2S)‐2‐[(E)‐2‐(4‐methylphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole against C6 were investigated, aiming to determine the region that the molecule is biologically active. Biological activities of mentioned molecules were investigated with molecular docking analyses. The appropriate target protein (PDB codes: 1 M17 for the HeLa cells and 1JQH for the C6 cells) was used for 2‐{(1S,2S)‐2‐[(E)‐2‐(2‐methoxyphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole and 2‐{(1S,2S)‐2‐[(E)‐2‐(4‐methylphenyl)ethenyl]cyclopent‐3‐en‐1‐yl}‐1,3‐benzothiazole molecules exhibiting the highest biological activity against HeLa and C6 cells in the docking studies. As a result, it was determined that these molecules are the best candidates for the anticancer drug.     

Efficient Preparation of (R)‐2‐chloromandelic Acid Via a Recycle Process of Resolution

Efficient preparation of (R)‐2‐chloromandelic acid (R)-1 based on a recycle process of resolution is described. In the process, the desired (R)-1 was obtained by coordination‐mediated resolution with D‐O,O'‐di‐(p‐toluoyl)‐tartaric acid in the presence of Ca²⁺. Meanwhile, the undesired (S)-1 could be racemized in the presence of sodium hydroxide and the product was suitable for further resolution. A carbanion mechanism for the racemization of (S)-1 is proposed. Chirality 27:281–285, 2015. © 2015 Wiley Periodicals, Inc.     

2‐Hydroxynaphthalene‐1‐carbaldehyde‐ and 2‐(Aminomethyl)pyridine‐Based Schiff Base CuII Complexes for DNA Binding and Cleavage

Three mononuclear Cu^II complexes, [CuCl(naph‐pa)] ( 1 ), [Cu(bipy)(naph‐pa)]Cl ( 2 ), and [Cu(naph‐pa)(phen)]Cl ( 3 ) ((naph‐pa)=Schiff base derived from the condensation of 2‐hydroxynaphthalene‐1‐carbaldehyde and 2‐picolylamine (=2‐(aminomethyl)pyridine), bipy=2,2′‐bypiridine, and phen=1,10‐phenanthroline) were synthesized and characterized. Complex 1 exhibits square‐planar geometry, and 2 and 3 exhibit square pyramidal geometry, where Schiff base and bipy/phen act as NNO and as NN donor ligands, respectively. CT (Calf thymus)‐DNA‐binding studies revealed that the complexes bind through intercalative mode and show good binding propensity (intrinsic binding constant K_b: 0.98×10⁵, 2.22×10⁵, and 2.67×10⁵ M ^?1 for 1 – 3 , resp.). The oxidative and hydrolytic DNA‐cleavage activity of these complexes has been studied by gel electrophoresis: all the complexes displayed chemical nuclease activity in the presence and absence of H₂O₂. From the kinetic experiments, hydrolytic DNA cleavage rate constants were determined as 2.48, 3.32, and 4.10 h^?1 for 1 – 3 , respectively. It amounts to (0.68–1.14)×10⁸‐fold rate enhancement compared to non‐catalyzed DNA cleavage, which is impressive. The complexes display binding and cleavage propensity to DNA in the order of 3 > 2 > 1 .     

Stopped‐Flow Enantioselective HPLC‐CD Analysis and TD‐DFT Stereochemical Characterization of Methyl Trans‐3‐(3,4‐Dimethoxyphenyl)Glycidate

Caffeic acid‐derived polyethers are a class of natural products isolated from the root extracts of comfrey and bugloss, which are endowed with intriguing pharmacological properties as anticancer agents. The synthesis of new polyether derivatives is achieved through ring‐opening polymerization of chiral 2,3‐disubstituted oxiranes, whose absolute configurations define the overall stereochemistry of the produced polymer. The absolute stereochemistry of one of these building blocks, methyl trans‐3‐(3,4‐dimethoxy‐phenyl)glycidate ( 3 ), was therefore characterized by the combination of enantioselective high‐performance liquid chromatography (HPLC), electronic circular dichroism (ECD) spectroscopy, and time‐dependent density functional theory (TD‐DFT) calculations. Initial efforts aiming at the isolation of enantiomers by means of a standard preparative HPLC protocol followed by offline ECD analysis failed due to unexpected degradation of the samples after collection. The stopped‐flow HPLC‐CD approach, by which the ECD spectra of enantiomers are measured online with the HPLC system, was applied to overcome this issue and allowed a fast, reliable, and chemical‐saving analysis, while avoiding the risks of sample degradation during the collection and processing of enantiomeric fractions. Subsequent TD‐DFT calculations identified ( (2S,3R)-3 as the first eluted enantiomeric fraction on the Lux Cellulose‐2 column, therefore achieving a full stereochemical characterization of the chiral oxirane under investigation. Chirality 27:914–918, 2015. © 2015 Wiley Periodicals, Inc.