A Simple Chiral Cu(II) Complex as an Effective Phase‐Transfer Catalyst for the Enantioselective Alkylation of Dissymmetric Glycinate Ketimines

Catalytic asymmetric benzylation of a dissymmetric tert‐butylglycinate ketimine, incorporating 1‐naphthyl and phenyl groups as the Schiff base substituents, under phase‐transfer conditions was investigated. It was interesting to note that the sense of asymmetric induction of the alkylation of Z‐imine stereoisomer is opposite to that of the corresponding E stereoisomer with a similar degree of enantioselectivity. More interestingly, the chiral Cu(II) complex of the Schiff base derived from (R)‐2‐phenylglycinol and 2‐hydroxy‐1‐naphthaldehyde was found to catalyze the same reaction under solid‐liquid conditions with comparable enantioselectivity (up to 60% ee) with respect to known cinchona alkaloid catalysts. The solvent/base‐system parameter was shown to control the optimal catalytic activity. Chirality 27:944–950, 2015. © 2015 Wiley Periodicals, Inc.     

A Simple Method for Resolution of Endo‐/Exo‐Monoesters of Trans‐Norborn‐5‐Ene‐2,3‐Dicarboxylic Acids Into Their Enantiomers

Separation of optical isomers obtainable from trans‐norborn‐5‐ene‐2,3‐dicarboxylic acid methyl and tert‐butyl monoesters was performed by crystallization of the respective salts prepared with (R)‐ and (S)‐1‐phenylethylamine. Starting from racemic endo‐monomethyl ester of trans‐norborn‐5‐ene‐2,3‐dicarboxylic acid, prepared by partial hydrolysis of the cyclopentadiene‐dimethyl fumarate adduct, the corresponding (2R,3R)‐endo‐monoester was isolated in 97% enantiomeric excess (ee) yield after seven repeated crystallizations from tetrachloromethane. Starting from exo‐mono‐tert‐butyl ester of the same acid, prepared by alcoholysis of the cyclopentadiene‐maleic anhydride adduct followed by isomerization, (2R,3R)‐exo‐monoester was isolated in >98% ee yield after four repeated crystallizations from ethanol. Crystallization of the acids from the mother liquor containing (S)‐1‐phenylethylamine yielded products with inverse stereochemical configuration. Chirality 27:151–155, 2015. © 2014 Wiley Periodicals, Inc.     

Lipase‐catalyzed kinetic resolution of novel antitubercular benzoxazole derivatives

Novel benzoxazole derivatives were synthesized, and their antitubercular activity against sensitive and drug‐resistant Mycobacterium tuberculosis strains (M. tuberculosis H₃₇Rv, M. tuberculosis sp. 210, M. tuberculosis sp. 192, Mycobacterium scrofulaceum, Mycobacterium intracellulare, Mycobacterium fortuitum, Mycobacterium avium, and Mycobacterium kansasii) was evaluated. The chemical step included preparation of ketones, alcohols, and esters bearing benzoxazole moiety. All racemic mixtures of alcohols and esters were separated in Novozyme SP 435‐catalyzed transesterification and hydrolysis, respectively. The transesterification reactions were carried out in various organic solvents (tert‐butyl methyl ether, toluene, diethyl ether, and diisopropyl ether), and depending on the solvent, the enantioselectivity of the reactions ranged from 4 to >100. The enzymatic hydrolysis of esters was performed in 2 phase tert‐butyl methyl ether/phosphate buffer (pH = 7.2) system and provided also enantiomerically enriched products (ee 88‐99%). The antitubercular activity assay has shown that synthesized compounds exhibit an interesting antitubercular activity. Racemic mixtures of alcohols, (±)‐4‐(1,3‐benzoxazol‐2‐ylsulfanyl)butan‐2‐ol ((±)‐ 3a ), (±)‐4‐[(5‐bromo‐1,3‐benzoxazol‐2‐yl)sulfanyl]butan‐2‐ol ((±)‐ 3b ), and (±)‐4‐[(5,7‐dibromo‐1,3‐benzoxazol‐2‐yl)sulfanyl]butan‐2‐ol ((±)‐ 3c ), displayed as high activity against M. scrofulaceum, M. intracellulare, M. fortuitum, and M. kansasii as commercially available antituberculosis drug‐Isoniazid. Moreover, these compounds exhibited twice higher activity toward M. avium (MIC 12.5) compared with Isoniazid (MIC 50).     

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.     

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.     

Isolation of Ceramides from Tagetes patula L. Yellow Flowers and Nematicidal Activity of the Fractions and Pure Compounds against Cyst Nematode,Heterodera zeae

Investigation of yellow flower extract of Tagetes patula L. led to the identification of an aggregate of five phytoceramides. Among them, (2R)‐2‐hydroxy‐N‐[(2S,3S,4R,8E)‐1,3,4‐trihydroxyicos‐8‐en‐2‐yl]icosanamide, (2R)‐2‐hydroxy‐N‐[(2S,3S,4R,8E)‐1,3,4‐trihydroxyicos‐8‐en‐2‐yl]heneicosanamide, (2R)‐2‐hydroxy‐N‐[(2S,3S,4R,8E)‐1,3,4‐trihydroxyicos‐8‐en‐2‐yl]docosanamide, and (2R)‐2‐hydroxy‐N‐[(2S,3S,4R,8E)‐1,3,4‐trihydroxyicos‐8‐en‐2‐yl]tricosanamide were identified as new compounds and termed as tagetceramides, whereas (2R)‐2‐hydroxy‐N‐[(2S,3S,4R,8E)‐1,3,4‐trihydroxyicos‐8‐en‐2‐yl]tetracosanamide was a known ceramide. A steroid (β‐sitosterol glucoside) was also isolated from the subsequent fraction. The structures of these compounds were determined on the basis of spectroscopic analyses, as well as chemical method. Several other compounds were also identified by GC/MS analysis. The fractions and some commercial products, a ceramide HFA, β‐sitosterol, and stigmasterol were evaluated against an economically important cyst nematode, Heterodera zeae. Ceramide HFA showed 100 % mortality, whereas, β‐sitosterol and stigmasterol were 40–50 % active, at 1 % concentration after 24 h of exposure time, while β‐sitosterol glucoside revealed no activity against the nematode.     

Enantiomeric Specificity of Biologically Significant Cu(II) and Zn(II) Chromone Complexes Towards DNA

Novel chiral Schiff base ligands (R)/(S)‐2‐amino‐3‐(((1‐hydroxypropan‐2‐yl)imino)methyl)‐4H‐chromen‐4‐one (L₁ and L₂) derived from 2‐amino‐3‐formylchromone and (R/S)‐2‐amino‐1‐propanol and their Cu(II)/Zn(II) complexes ( R1 , S1 , R2 , and S2 ) were synthesized. The complexes were characterized by elemental analysis, infrared (IR), hydrogen (¹H) and carbon (¹³C) nuclear magnetic resonance (NMR), electrospray ionization‐mass spectra (ESI‐MS), and molar conductance measurements. The DNA binding studies of the complexes with calf thymus were carried out by employing different biophysical methods and molecular docking studies that revealed that complexes R1 and S1 prefers the guanine–cytosine‐rich region, whereas R2 and S2 prefers the adenine–thymine residues in the major groove of DNA. The relative trend in K_b values followed the order R1 S1 R2 S2 . This observation together with the findings of circular dichroic and fluorescence studies revealed maximal potential of (R)‐enantiomeric form of complexes to bind DNA. Furthermore, the absorption studies with mononucleotides were also monitored to examine the base‐specific interactions of the complexes that revealed a higher propensity of Cu(II) complexes for guanosine‐5′‐monophosphate disodium salt, whereas Zn(II) complexes preferentially bind to thymidine‐5′‐monophosphate disodium salt. The cleavage activity of R1 and R2 with pBR322 plasmid DNA was examined by gel electrophoresis that revealed that they are good DNA cleavage agents; nevertheless, R1 proved to show better DNA cleavage ability. Topoisomerase II inhibitory activity of complex R1 revealed that the complex inhibits topoisomerase II catalytic activity at a very low concentration (25 μM). Furthermore, in vitro antitumor activity of complexes R1 and S1 were screened against human carcinoma cell lines of different histological origin. Chirality 24:977–986, 2012. © 2012 Wiley Periodicals, Inc.     

Enantiomeric 4‐Acylamino‐6‐alkyloxy‐2 Alkylthiopyrimidines As Potential A3 Adenosine Receptor Antagonists: HPLC Chiral Resolution and Absolute Configuration Assignment by a Full Set of Chiroptical Spectroscopy

The chiral separation of enantiomeric couples of three potential A₃ adenosine receptor antagonists: (R/S)‐N‐(6‐(1‐phenylethoxy)‐2‐(propylthio)pyrimidin‐4‐yl)acetamide ( 1 ), (R/S)‐N‐(2‐(1‐phenylethylthio)‐6‐propoxypyrimidin‐4‐yl)acetamide ( 2 ), and (R/S)‐N‐(2‐(benzylthio)‐6‐sec‐butoxypyrimidin‐4‐yl)acetamide ( 3 ) was achieved by high‐performance liquid chromatography (HPLC). Three types of chiroptical spectroscopies, namely, optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD), were applied to enantiomeric compounds. Through comparison with Density Functional Theory (DFT) calculations, encompassing extensive conformational analysis, full assignment of the absolute configuration (AC) for the three sets of compounds was obtained. Chirality 28:434–440, 2016. © 2016 Wiley Periodicals, Inc.     

DNA/HSA interaction and nuclease activity of an iron(III) amphiphilic sulfonated corrole

The DNA binding of amphiphilic iron(III) 2,17‐bis(sulfonato)‐5,10,15‐tris(pentafluorophenyl)corrole complex (Fe–SC) was studied using spectroscopic methods and viscosity measurements. Its nuclease‐like activity was examined by using pBR322 DNA as a target. The interaction of Fe–SC with human serum albumin (HSA) in vitro was also examined using multispectroscopic techniques. Experimental results revealed that Fe–SC binds to ct‐DNA via an outside binding mode with a binding constant of 1.25 × 10⁴ M^–1. This iron corrole also displays good activity during oxidative DNA cleavage by hydrogen peroxide or tert‐butyl hydroperoxide oxidants, and high‐valent (oxo)iron(V,VI) corrole intermediates may play an important role in DNA cleavage. Fe–SC exhibits much stronger binding affinity to site II than site I of HSA, indicating a selective binding tendency to HSA site II. The HSA conformational change induced by Fe–SC was confirmed by UV/Vis and CD spectroscopy. Copyright © 2015 John Wiley & Sons, Ltd.     

Tyrosinase‐Mediated Formation of a Reactive Quinone from the Depigmenting Agents, 4‐tert‐Butylphenol and 4‐tert‐Butylcatechol

Exposure of the skin to certain phenols or catechols such as 4‐tert‐butylphenol (TBP) and 4‐tert‐butylcatechol (TBC) may cause leukoderma. These substances are used in the polymer industry and numerous cases have been reported. Several theories of the mechanism for chemical leukoderma have been suggested. In the present study, TBP and TBC are shown to be oxidised by tyrosinase. The oxidation of TBC yields a quinone that is further investigated on its reactions with cysteine or glutathione (GSH). The products formed are isolated and identified by mass spectrometry and nuclear magnetic resonance as being 4‐tert‐butyl‐6‐S‐cysteinylcatechol (cys‐TBC) and 4‐tert‐butyl‐6‐S‐glutathionylcatechol (GS‐TBC). The reactive quinone is a strongly electrophilic substance that rapidly reacts with GSH. A depletion of the GSH defence system may give conditions where the quinone lives long enough to effect its toxic properties. The influence of the reactive tert‐butylquinone on enzymatic activities is demonstrated by the inhibition of glyceraldehyde‐3‐phosphate dehydrogenase.     

Synthesis and evaluation of in vivo anti‐hypothermic effect of all stereoisomers of the thyrotropin‐releasing hormone mimetic: Rovatirelin Hydrate

We discovered the orally active thyrotropin‐releasing hormone (TRH) mimetic: (4S,5S)‐5‐methyl‐N‐{(2S)‐1‐[(2R)‐2‐methylpyrrolidin‐1‐yl]‐1‐oxo‐3‐(1,3‐thiazol‐4‐yl)propan‐2‐yl}‐2‐oxo‐1,3‐oxazolidine‐4‐carboxamide 1 (rovatirelin). The central nervous system (CNS) effect of rovatirelin after intravenous (iv) administration is 100‐fold higher than that of TRH. As 1 has four asymmetric carbons in its molecule, there are 16 stereoisomers. We synthesized and evaluated the anti‐hypothermic effect of all stereoisomers of 1 , which has the (4S),(5S),(2S),(2R) configuration from the N‐terminus to the C‐terminus, in order to clarify the structure?activity relationship (SAR) of stereoisomers. The (4R),(5R),(2R),(2S)‐isomer 16 did not show any anti‐hypothermic effect. Only the (4S),(5S),(2S),(2S)‐isomer 10 , which has the (2S)‐2‐methylpyrrolidine moiety at the C‐terminus showed the anti‐hypothermic effect similar to 1 . Stereoisomers, which have the (5R) configuration of the oxazolidinone at the N‐terminus and the (2R) configuration at the middle‐part, showed a much lower anti‐hypothermic effect than that of 1 . On the other hand, stereoisomers, which have the (4R) configuration of the oxazolidinone at the N‐terminus or the (2S) configuration of the C‐terminus, have little influence on the anti‐hypothermic effect.     

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.     

Hydrolytic resolution of (R,S)-2-hydroxycarboxylic acid esters in biphasic media: implication for rate-limiting formation or breakdown of tetrahedral intermediates in acylation step

A thermally stable esterase (SNSM‐87) from Klebsiella oxytoca is explored as an enantioselective biocatalyst for the hydrolytic resolution of (R,S)‐2‐hydroxycarboxylic acid esters in biphasic media, where the best methyl esters possessing the highest enantioselectivity and reactivity are selected and elucidated in terms of the structure–enantioselectivity correlations and substrate partitioning in the aqueous phase. With (R,S)‐2‐chloromandelates as the model substrates, an expanded Michaelis–Menten mechanism for the rate‐limiting acylation step is adopted for the kinetic analysis. The Brønsted slope of 25.7 for the fast‐reacting (S)‐2‐chloromandelates containing a difficult leaving alcohol moiety, as well as that of 4.13 for the slow‐reacting (R)‐2‐chloromandelates in the whole range of leaving alcohol moieties, indicates that the breakdown of tetrahedral intermediates to acyl‐enzyme intermediates is rate‐limiting. However, the rate‐limiting step shifts to the formation of tetrahedral intermediates for the (S)‐2‐chloromandelates containing an easy leaving alcohol moiety, and leads to an optimal enantioselectivity for the methyl ester substrate. Biotechnol. Bioeng. 2007; 98: 30–38. © 2007 Wiley Periodicals, Inc.     

Acridone Alkaloids from Swinglea glutinosa (Rutaceae) and Their Effects on Photosynthesis

Continuing our search for herbicide models based on natural products, we investigated the action mechanisms of five alkaloids isolated from Swinglea glutinosa (Rutaceae): Citrusinine‐I ( 1 ), glycocitrine‐IV ( 2 ), 1,3,5‐trihydroxy‐10‐methyl‐ 2,8‐bis(3‐methylbut‐2‐en‐1‐yl)‐9(10H)‐acridinone ( 3 ), (2R)‐2‐tert‐butyl‐3,10‐dihydro‐4,9‐dihydroxy‐11‐methoxy‐10‐methylfuro[3,2‐b]acridin‐5(2H)‐one ( 4 ), and (3R)‐2,3,4,7‐tetrahydro‐3,5,8‐trihydroxy‐6‐methoxy‐2,2,7‐trimethyl‐12H‐pyrano[2,3‐a]acridin‐12‐one ( 5 ) on several photosynthetic activities in an attempt to find new compounds that affect photosynthesis. Through polarographic techniques, the compounds inhibited the non‐cyclic electron transport in the basal, phosphorylating, and uncoupled conditions from H₂O to methylviologen (=MV). Therefore, they act as Hill reaction inhibitors. This approach still suggested that the compounds 4 and 5 had their interaction site located at photosystem I. Studies on fluorescence of chlorophyll a suggested that acridones ( 1 – 3 ) have different modes of interaction and inhibition sites on the photosystem II electron transport chain.     

Practical access to the proline analogs (S,S,S)- and (R,R,R)-2-methyloctahydroindole-2-carboxylic acids by HPLC enantioseparation

An efficient methodology for the preparation of the α‐tetrasubstituted proline analog (S,S,S)‐2‐methyloctahydroindole‐2‐carboxylic acid, (S,S,S)‐(αMe)Oic, and its enantiomer, (R,R,R)‐(αMe)Oic, has been developed. Starting from easily available substrates and through simple transformations, a racemic precursor has been synthesized in excellent yield and further subjected to HPLC resolution using a cellulose‐derived chiral stationary phase. Specifically, a semipreparative (250 mm × 20 mm ID) Chiralpak® IC column has allowed the efficient resolution of more than 4 g of racemate using a mixture of n‐hexane/tert‐butyl methyl ether/2‐propanol as the eluent. Multigram quantities of the target amino acids have been isolated in enantiomerically pure form and suitably protected for incorporation into peptides. Chirality, 2011. © 2011 Wiley‐Liss, Inc.     

Enantioselective liquid‐liquid extraction of DL‐mandelic acid using chiral diphosphine ligands as extractants

In order to expand the application range of chiral diphosphine ligands, (S)‐BINAP, (S)‐SEGPHOS, and (S)‐MeO‐BIPHEP were employed as extractants to recognize DL‐mandelic acid. The results indicated that (S)‐SEGPHOS‐Cu exhibited considerable ability to recognize DL‐mandelic acid with operational enantioselectivity (α) of 2.677. The process of extraction of DL‐mandelic acid using (S)‐SEGPHOS‐Cu as extractant was systematically investigated. Performance factor (pf) was adopted to comprehensively evaluate the extraction. After optimization by response surface methodology (RSM), the optimal extraction condition is temperature of 5.5°C, (S)‐SEGPHOS‐Cu concentration of 3.0 mmol/L, and pH of 8.0. And the predicted and experimental maximum values of pf were 0.26374 and 0.26839, respectively.     

Polymer‐Supported Optically Active fac(S)‐Tris(thiotato)rhodium(III) Complex for Sulfur‐Bridging Reaction With Precious Metal Ions

The optically active mixed‐ligand fac(S)‐tris(thiolato)rhodium(III) complexes, Δ_L‐fac(S)‐[Rh(aet)₂(L‐cys‐N,S)]^? (aet = 2‐aminoethanethiolate, L‐cys = L‐cysteinate) ( 1 ) and Δ_LL‐fac(S)‐[Rh(aet)(L‐cys‐N,S)₂]^2? were newly prepared by the equatorial preference of the carboxyl group in the coordinated L‐cys ligand. The amide formation reaction of 1 with 1,10‐diaminodecane and polyallylamine gave the diamine‐bridged dinuclear Rh(III) complex and the single‐chain polymer‐supported Rh(III) complex with retention of the Δ_L configuration of 1 , respectively. These Rh(III) complexes reacted with Co(III) or Co(II) to give the linear‐type trinuclear structure with the S‐bridged Co(III) center and the two Δ‐Rh(III) terminal moieties. The polymer‐supported Rh(III) complex was applied not only to the CD spectropolarimetric detection and determination of a trace of precious metal ions such as Au(III), Pt(II), and Pd(II) but also to concentration and extraction of these metal ions into the solid polymer phase. Chirality 28:85–91, 2016. © 2015 Wiley Periodicals, Inc.     

Enzymatic Hydrolysis of Esters Containing a Tetrazole Ring

The lipase‐catalyzed enantioselective hydrolysis of acetates containing tetrazole moiety was studied. Among all tested lipases, Novozyme SP 435 allowed to obtain optically active 4‐(5‐aryl‐2H‐tetrazol‐2yl)butan‐2‐ol and 1‐(5‐aryl‐2H‐tetrazol‐2yl)‐propan‐2‐ol and their acetates with the highest optical purities (ee = 95%‐99%) and excellent enantioselectivity (E>100). Some of the synthesized tetrazole derivatives were screened for their antifungal activity. Racemic mixtures of 4‐[5‐(4‐chlorophenyl)‐2H‐tetrazol‐2‐yl)butan‐2‐ol as well as pure enantiomers of this compound showed promising antifungal activity against F. sambucinum, F. oxysporum, C. coccodes, and A. niger. Chirality 26: 811–816, 2014. © 2014 Wiley Periodicals, Inc.     

Incorporation of β‐amino acids into ascidiacyclamides: Effects on conformation,cytotoxicity and interaction with copper (II) ion

Seven ascidiacyclamide [cyclo(–Ile–oxazoline–d ‐Val–thiazole–)₂] (ASC) analogues incorporating the β‐amino acids βIle, βoxazoline, and/or d ‐βVal were synthesized. We then investigated the effects of the position and number of incorporated β‐amino acids on the structure, cytotoxicity, and copper binding by these seven analogues. The structural analyses revealed that both βIle and d ‐βVal favor a gauche‐type θ torsion angles, while βoxazoline favors a trans‐type θ torsion angle. Expansion of the macrocycle by incorporation of βIle or d ‐βVal readily induced molecular folding. On the other hand, the incorporation of two βoxazoline residues strongly extended the peptide conformation, and the incorporation of one was sufficient for the moderate restriction important for conformational equilibrium and cytotoxicity. Despite expansion of the macrocycles, the structure‐cytotoxicity relationships were largely maintained. In studies of complexation of the analogues with Cu (II) ion, the position and number of incorporated β‐amino acids had a large impact on the structure of the metal complex and may contribute to its stabilization.