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Notes: The fate of an insect juvenile hormone analog applied to the insect body of the flesh fly (Sarcophaga bullata) or the tsetse fly (Glossina palpalis), respectively, was studied using three different radiolabeled positions in the parent biologically active compound 1. Several metabolites were found and analyzed. A mechanism of degradation of the applied molecule was designed using a combination of several radioanalytical methods. A unique monitoring of the applied compound and its metabolites was provided, based on the different radiolabeling of the structure (cf. 1a-1c), and established their fate in an insect body during a 10-day experiment. A 14C and 3H radiolabeling, respectively, was employed to synthesize three different radiolabeled forms 1a-1c derived from the parent non-labeled 1. A combination of three different ways of radiolabeling resulted in an advantage in tracing the metabolic pathway of degradation of the employed compound 1 in its radiolabeled forms 1a-1c.

Notes: Previous work has indicated orbital-symmetry effects upon forward electron transfer in bimolecular systems, with magnitude similar to that encountered in rigid monomolecular systems. The present work, which employs back electron transfer, supports and extends these earlier findings.

Notes: According to ab-initio calculations, the CF…HO H-bond in 1,3-diaxial 3-fluorocyclohexanol is characterized by d(F…H) = 2.08 Å, and ∠ (F…H—O) = 138°, and by ΔE between 1.2 and 4.1 kcal/mol, depending upon the reference system. Relative to the OH stretching frequency of axial cyclohexanol, the OH stretching frequency of 1,3-diaxial 3-fluorocyclohexanol is shifted by Δω = 7 cm-1. The rigid fluoro diols D-4 and L-4 were prepared from tetrahydroxy-p-benzoquinone in 11 steps and 1% overall yield. The IR spectrum of 4 in CCl4 soln. is characterized by Δν = 7 cm-1 for the axial and Δν = 44 cm-1 for the equatorial OH group. A relatively strong intramolecular CF…HO bond of 4 in CCl4 is evidenced by the large through-space coupling 5J(F,HO) of 9.3 Hz. Nevertheless, this FHO bond is disrupted in ethereal solvents, while the bifurcated O…HO bond subsists. In CCl4, the carbene generated from the glucosylidene-derived diazirine 5 reacted more rapidly with the axial OH group of D-4 and L-4 than with the equatorial one. This regioselectivity is in keeping with the weaker H-bond of the axial OH group. The regioselectivity is lower in ethers, but its solvent dependence does not parallel solvent basicity. This is not satisfactorily explained by the differential interaction of the ether solvents with the axial and equatorial OH groups, as evidenced by the solvent dependence of their chemical shift, but must also reflect the different interaction of the solvents with the carbene derived from 5, leading to ylides. The lower solvent dependence of the anomeric selectivity for the glycosidation of the equatorial OH group is a consequence of the coordination of the intermediate oxycarbenium ion with O—C(1) and O—C(3) rather than with the solvent. Under conditions of competitive glycosylation in CCl4, the fluoro alcohol D-22 reacted more slowly than the alcohol L-24, evidencing the intramolecular F…HO H-bond.

Notes: Khusimone (1), one of the main odor-donating compounds of vetiver oil, is subject of the following study on structure/odor relationship. The omittance of the methano bridge of the tricyclic khusimone should lead to the bicyclic partial structure (-)-2. Unexpectedly, (-)-2 could not be obtained since epimerization favored (-)-16. The stereochemical key step of the synthesis of the hydrazulene nucleus is based on a highly diastereoselective conjugate addition to a chiral oxocyclopent-1-ene-1-carboxylate.

Notes: A convenient preparation of (1R,2S,3R,4S)-3-(neopentyloxy)isoborneol (= (1R,2S,3R,4S)-3-(2,2-dimethyl-propoxy)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol; 1a), a valuable chiral auxiliary, is described. The synthesis involves six steps starting from the readily available camphorquinone (5) and gives 1a in 48% overall yield. The key step is the chemoselective hydrolysis of the less hindered 1,3-dioxolane moiety in the camphorquinone di-acetal 4.

Notes: A novel general synthesis of 2,4,5-tri- and 2,4,5,6-tetrasubstituted pyrimidines 5a-d and 7a, e, f, g by condensation of thiouronium salts of type 3 with (ethoxymethylidene)malononitrile (4) and [bis(methylthio)methylidene]malononitrile (6), respectively, was first established in solution (Scheme 1) and successfully transferred onto solid support by using the polymer-bound thiouronium salt 11 (Scheme 3). Further investigations were directed toward a multidirectional cleavage procedure of the 2-(alkylsulfinyl) intermediates, obtained from the 2-(alkylthio)pyrimidines 7a (Scheme 2) or 12 and 14 (Schemes 3 and 4), with different nucleophiles to form highly substituted pyrimidines. In addition, fused-heterocycle derivatives 22a--h, 24a-c, and 26a-e were generated in good-to-excellent yields by condensation of 7a, e, h with versatile isocyanates and isothiocyanates, with subsequent alkylation (Scheme 5).

Notes: Introduction of the non-complexing chiral (S)-2-methylbutoxy substituent close to the complexing site of a bis[(bipyridinyl)methoxy]calixarene podand resulted in the induction of an enantiomeric excess of ca. 30 % in the corresponding chiral CuI complex. Structural investigations by high-resolution NMR studies led us to propose the left-handed prohelical [CuI(bpy)2] substructure for the major enantiomer.

Notes: The insecticidal polyether antibiotic X-206 (1) complexes potassium ions using nearly all of its O-atoms either for binding to the metal ion or for participation in a H-bonding network which helps to hold X-206 in the ionophoric tertiary structure. The group OH—C(22) is not involved in these processes. It was supposed that derivatization of this group would not affect the ionophoric properties and would produce insecticidally active compounds. The chemistry leading to selective modification of OH—C(22) via the intermediate 6 was developed. The potassium-binding properties and insecticidal activities of the MeCOO—C(22) and MeO—C(22) compounds 3 and 11, respectively, confirmed that derivatization of the peripheral OH—C(22) was a valid strategy for the synthesis of biologically active compounds.

Notes: The lactam 21 was obtained in an overall yield of 72% from the hydroxy amide 16 by oxidation with the Dess-Martin periodinane, acid-catalysed isomerization of the oxidation products in toluene, whereupon 18/19 precipitated, and reductive dehydroxylation of 18/19 (Et3SiH/BF3 · OEt2; Scheme 1). The amide 16 was obtained by ammonolysis of the N-acetylglucosamine-derived lactone 15. Depending on the oxidation method, 16 yielded the keto amide 17, the hydroxy lactams 18/19, and the pyrrolidinecarboxamide 20 in widely different proportions. The pyrrolidinecarboxamide 20 was not reduced under the conditions of the reductive dehydroxylation. Hydrogenolysis of the benzyl-protected lactam 21 gave the trihydroxy lactam 22, while reduction with NaBH4/BF3 · OEt2 led to the 2-acetamidopiperidine derivative 24 (Scheme 2). Selective (tert-butoxy)carbonylation of the lactam 21 (→ 25) followed by NaBH4 reduction and acid-catalysed solvolysis in EtOH led to the α-ethoxycarbamates 28/29. Similarly, (tert-butoxy) carbonylation of 1 (→ 31) followed by reduction to 32/33 and glycosidation yielded the ethoxycarbamate 34. Treatment of the GlcNAc-derived ethyl glycosides 28/29 with Me3SiCN/BF3 · OEt2 gave the equatorial amino nitrile 30. Under similar conditions, the Glc-derived glycoside 34 led to the iminooxazolidinone 35. In the presence of a larger proportion of Me3SiCN at 5°, 34 was transformed into the axial, selectively monodebenzylated amino nitrile 36.

Notes: The reaction of 2-(trimethylsilyl)thiazole (2-TST) with several ketones was tested in the presence or absence of aldehydes. The keto aldehyde 5 (Scheme 2) was prepared from 1 via the hydroxy aldehyde 4 in 3 steps. It reacted with 2-TST to give, after desilylation and acetylation, the bis-thiazole 6. The ketone 11, obtained from 4 in 3 steps, reacted with 2-TST to give, after desilylation, 12. The ketofuranose 17 (Scheme 3) reacted with 2-TST to yield exclusively the more stable D-gluco epimer 18. The reaction of the ketone 11 (Scheme 2) with 2-TST was faster in the presence of 1 equiv. of the keto aldehyde 5, suggesting that an aldehyde promotes the indirect and intermolecular addition of 2-TST to a ketone. We have studied the effect of several aldehydes on the rate of the reaction of the ketones 11 and 17 with 2-TST at different temperatures and at different concentrations of the ketones and of the aldehydes. Electrophilic aldehydes, and particularly 2-fluorobenzaldehyde (0.1 equiv.), promote the addition of 2-TST to electrophilic ketones.

Notes: The synthesis of the Fmoc-protected amino acid 2 is presented. First attempts of amide-bond formation to the homodimer 4 in solution showed only poor coupling yields indicative for the low reactivity of the amino and carboxy groups in the building blocks 1 and 2, respectively (Scheme 1). Best coupling yields were found using dicyclohexylcarbodiimide (DCC) without any additive. The oligomerization of building block 2 adopting the Fmoc ((9H-fluoren-9-ylmethoxy)carbonyl) solid-phase synthesis yielded a mixture of N-terminal-modified distamycin-NA derivatives. By combined HPLC and MALDI-TOF-MS analysis, the N-terminal functional groups could be identified as acetamide and N,N-dimethylformamidine functions, arising from coupling of the N-terminus of the growing chain with residual AcOH or DCC-activated solvent DMF. An improved preparation of building block 2 and coupling protocol led to the prevention of the N-terminal acetylation. However, ‘amidination’ could not be circumvented. A thus isolated tetramer of 2, containing a lysine unit at the C-terminus and a N,N-dimethylformamidine-modified N-terminus, not unexpectedly, showed no complementary base pairing to DNA and RNA, as determined by standard UV-melting-curve analysis.

Notes: (S)-4,4,4-Trifluoro-3-hydroxybutanoic acid was used as a starting material for the synthesis of dendritic branches (16-21, 30-32) which were attached to a chiral triol (6 or ent-6), derived from (R)-3-hydroxybutanoic acid, to give CF3-substituted dendrimers (33-36, 38-40) and dendritic compounds (37) of 1st and 2nd generation. The key steps in these syntheses are diastereoselective aldol additions of dioxanone enolates (building blocks and intermediates 6-15, 22, 23, and 25-28) and Williamson etherifications of benzylic-branch bromides with triols (intermediates and products 16-21, 28, and 30-40). The surfaces of the dendrimers are covered with MeO (33-35, 38-40) or allyloxy groups (36 and 37). The new dendrimers are characterized by NMR and mass spectroscopy. 19F-NMR Signals of the CF3 groups reveal constitutional heterotopicities caused by substituents which are separated from the F-nuclei by up to 15 bonds (through a 1,1′-biphenyl-4,4′-diyl spacer!) (Fig. 6).

Notes: An explanation for the very high diastereoselectivity observed for the reactions of carbonyl-substituted (arylsulfinyl)methyl radicals is presented, based on experimental results and semiempirical calculations. The influence of dipole-dipole interactions, allylic 1,3-strain (A1,3 strain), allylic 1,2-strain (A1,2 strain), and coulombic interactions is discussed based on stereoselectivities observed with (alkoxycarbonyl)-, cyano-, and aryl-substituted (arylsulfinyl)methyl radicals. In the second part, the effect of solvents and Lewis acids on the stereoselectivity of reactions of (arylsulfinyl)- and (alkylsulfinyl)benzyl radicals has been examined.

Notes: Compounds 6-13 were prepared starting from 1-(triphenlymethyl)-protected 1H-imidazoles 14 and 15 in several steps. Lithiation with BuLi in THF followed by reaction with (triphenylmethoxy)acetaldehyde (16) afforded 17 and 18, respectively. O-Methylation of 17 and 18 gave diethers 19 and 20, respectively. The N- and O-trityl protecting groups of 17-20 were cleaved by acid treatment to give deprotected compounds 21-24. Acylation with equimolar amounts (for mono- or di-O-acylation) of the corresponding acyl chlorides yielded 1H-imidazoles 6-13. Compounds 7, 8, 10, and 11 exhibited moderate protein kinase C inhibition.

Notes: The indolomorphinans 4-7 were prepared from their corresponding morphinan-6-one derivatives 8-11 via Fischer indole synthesis. Compounds 4 and 5 exhibited higher antagonist potency at δ opioid receptors in the mouse vas deferens preparation than the reference drug HS 378 (2), while compounds 6 and 7 were less potent.

Notes: 8-Fluoro-6-(methoxymethoxy)quinoline (1) was synthesized, and the reactivity of 1 against organolithium compounds was studied under different reaction conditions. With BuLi, directed ortho-metalation (DoM) was accompanied by 1,2-addition to the C=N bond. 1,2-Addition was exclusively observed with t-BuLi. Selective ortho-metalation was achieved with MeLi (Table). Based on these findings, a short and high-yielding synthesis of the highly functionalized quinolines 12a-c was developed.

Notes: The new derivatives 7a-c, of vitamin B12, with a peripheral tris(oxyethylene) chain linked to the corrin ring by an amide or ester group, are prepared, and their ligand-exchange reactions are investigated. Upon reduction of the aqua-cyano complexes 8a-c with NaBH4, cleavage of the ‘outer’ ester and amide group is observed.

Notes: Investigation of the inhibition of δ-chymotrypsin with the four novel, optically active, axially and equatorially substituted cis-3-(2,4-dinitrophenoxy)-2,4-dioxa-3λ5-phosphabicyclo[4.4.0]decan-3-ones (= 3-(2,4-dinitrophenoxy)hexahydro-4H-1,3,2-benzodioxaphosphorin 2-oxides) showed only the equatorially substituted enantiomer (-)-4b to be an irreversible inhibitor of the enzyme, and (-)-4b at pH 7.8 revealed a quickly rising resonance at -2.49 ppm assigned to the hydrolysis product 8 and later, while inhibition proceeded, a second one at -4.08 ppm. attributed to the δ-chymotrypsin adduct 7 (Scheme 3). Comparision of the latter signal with the 31P-NMR chemical shifts of the covalent phosphoserine model compounds (-)-6a (-5.67 ppm, axial substitution) and (+)-6b (-4.02 ppm, equatorial substitution) suggests that the inhibition proceeded via neat retention of the configuration at the P-atom of (-)-4b yielding the equatorially substituted covalent Ser195 adduct 7.

Notes: The synthesis of 8-azaadenosine (1a; z8A) has been performed by SnCl4-catalyzed glycosylation of 8-azaadenine (4) with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose (5), followed by the separation of the regioisomers 6 and 7 and subsequent deacetylation. The ribonucleoside 1a as well as its 2′-deoxy derivative 1b (z8Ad) were converted into oligonucleotide building blocks-the phosphonate 2 as well as the phosphoramidites 3 and 19. They were used to prepare the oligoribonucleotide (z8A-U)6 and oligodeoxyribonucleotides. The Tm values and the thermodynamic data of duplex formation of the modified duplexes showed no significant changes compared to those containing Ad or A residues. This indicates that the stereoelectronic effect of the 8-azaadenine base which was found for the monomeric nucleoside has only a minor influence on the duplex stability.

Notes: Short, dye-labeled oligonucleotides have been used as primers in template-controlled polymerization reactions of RNA. The synthesis of appropriate acridine derivatives and their attachments to nucleic acids is described. In the nonenzymatic oligomerization of 2-methyl-1H-imidazole-activated guanosine 5′-monophosphate, two observations deserve special notice: (1) reaction rates are almost unchanged by variations of the Na+ concentration; (2) the conformational type of the primer-template duplex (A vs. B) has considerable influence on the rates and yields of RNA oligomerization. When the incorporation of cytidine was studied in the presence of 1M Na+ or K+, the process was almost inhibited by quadruplex formation of the oligo-dG template. However, if these cations were omitted, an efficient primer extension could be observed using template concentrations as high as 100 μM. The chances for nonenzymatic self-replication of RNA thus might be distinctly better than previously assumed.

Notes: The reaction of ω-keto amides with Lawesson's reagent (LR: 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide) is described. Treatment of 3-keto amides (2-acylacetamides) 1 with LR gave the corresponding 3-keto thioamides 2, along with 1,2-dithiole-3-thiones 3. Treatment of 4-keto amides, 3-acyl propionamides 5, with LR yielded five-membered heterocycles, pyrroles 6 and/or 2-aminothiophenes 7. 5-Keto amides, 3-benzoyl butyramides 8, reacted with LR to give dihydrothiopyran-2-thione 9 as the sole product, but in low yield. 2-Acylbenzamides 10 also reacted with LR to afford 3-mercaptoisoindolin-2-ones 11 or dihydroisobenzothiophene-1-thiones 12.

Notes: A novel and more efficient synthesis of 14-alkoxy-substituted indolo- and benzofuro-morphinans in three steps starting from either naltrindole (1) or naltriben (2), using methoxymethyl or silyl protecting groups, is reported. The 14-O-alkyl group is introduced at the penultimate step of the procedure. This is an additional advantage of the described procedure since the late introduction of the 14-O-alkyl group makes it much easier to produce a greater diversity of 14-alkoxy derivatives in this series of δ opioid receptor antagonists. Thus, compounds 14-19, 20-25, and 27-29 were synthesized.

Notes: Variously β-substituted (2R)-N-[(E)-α,β-enoyl]bornane-10,2-sultams were oxidized with OsO4/4-methylmorpholine 4-oxide in a highly stereoselective manner. In all cases, the attack occurred on the C(α)-re face. The absolute configurations of all products were determined by chemical correlation. Mechanistic considerations about the reactive conformation as well as fully refined X-ray crystal structures of the dihydroxylated products are discussed. New neutral conditions for sultam acylation, applicable to the preparation of the taxol and Taxotere® C(13) side chain as well as of Cardizem® and chloramphenicol precursors, are also presented.

Notes: α-Bromination of 9-acetoxy rubanone 2 and subsequent reaction with secondary amines gave bicyclic α-amino ketones as a kinetic product and a 4-oxa-1-azatwistan-2-one 6 under thermodynamic conditions. This two-step procedure represents a concise 1,2-carbonyl transposition and provides a short route to lactam alkaloids.

Notes: Macrocyclic [4n + 2]-Hückel Aromatic Systems up to n = 9 and [4n] Antiaromatic Systems up to n = 10: Homologous Sequences from Tetraepoxy[24]annulene(2.0.2.0) to Tetraepoxy[40]annulene(12.0.12.0) and from the ‘Tetraoxa[22]porphyrin(2.0.2.0)-’ to the ‘Tetraoxa[38]porphyrin(12.0.12.0’-Dication1)2)Tetraepoxy[32]annulene(8.0.8.0) 3, tetraepoxy[36]annulene(10.0.10.0) 4, and tetraepoxy[40]annulene(12.0.12.0) 5 are synthesized and oxidized to give the ‘tetraoxa[30]-’, ‘tetraoxa[34]-’, and ‘tetraoxa[38]porphyrin’ dications 8-10. The annulenes as well as the ‘porphyrins’ are mixtures of at least two different configurational isomers, which can be analyzed by 1H-NMR techniques. Together with systems described already earlier, a complete homologous sequence from tetraepoxy[24]annulene(2.0.2.0) to tetraepoxy[40]annulene(12.1.12.0) and from ‘tetraoxa[22]porphyrin(2.0.2.0)’ to ‘tetraoxa[38]porphyrin(12.0.12.0)’ dications are available for the first time. The UV/VIS-absorptionmaxima in the annulene series are shifted to longer wavelengths with an increment of 12 nm per additional C=C bonds, and the Δδ values of the 1H-NMR spectra demonstrate a decreasing paratropic character (Δδ = 5.97 (1), 2.80 (3), and 4.23 ppm (4). The averaged λmax values of the Soret bands of the ‘tetraoxaporphyrin’ dications show a linear bathochromic shift with an increment Δδ of 58 nm per two additional double bonds, the absorptions of the most intensive Q-bands also increase linearly with an increment of ca. 160 nm. The Δδ values of the 1H-NMR spectra of the ‘tetraoxaporphyrin’ dications are increasing with the ring size (Δδ = 24.04 (7a) to 25.17 (9a) ppm), respectively, decreasing (Δδ = 21.55 (6) to 21.50 (9b) ppm) with a small maximum of 22.60 ppm for 7b, depending on the configuration of the isomers. The results confirm the antiaromatic character of the annulenes with up to 40π electrons and the aromatic character of the ‘tetraoxaporphyrin’ dications with up to 38π electrons.

Notes: A broad variety of new acyclic vinyl ethers (see 6-41) have been synthesized via the vinyl-interchange reaction of ethyl vinyl ether at room temperature using mercury(II) trifluoroacetate as a highly efficient catalyst. The appropriate vinyl ethers were reacted under acidic conditions with 3′,5′-O-silyl-protected uridine 42 to the corresponding 2′-O-(1-alkoxyethyl) derivatives 43-83 which gave, on desilylation of F- ions, in high yields the uridine-2′-O-acetal derivatives 84-124. The relative stabilities of the newly synthesized compounds under acidic and basic conditions were determined using TLC and HPLC techniques. Protected protecting groups offer the best properties for oligoribonucleotide syntheses. Interestingly, the very acid-stable acetals of the β-substituted ethyl-type 118-121 and 123 can be cleaved by a β-elimination process providing a series of base-labile acetals of potential synthetic value.

Notes: Enantioselectivity of acetylation by vinyl acetate/AcOEt catalyzed by immobilized Candida antarctica lipase (Novozym 435) is studied for rac-3-(hydroxymethyl)-1,4-benzodiazepin-2-ones 7, 9, 14 (n = 1; number of CH2 groups in the chain at C(3)), 20 (n = 2), and for prochiral 3,3-bis(hydroxymethyl) derivative 16. Enantiomeric excess (ee [%]) is correlated with conformational properties of substrates (relative conformation, energy difference between two boat-like ground-state conformations, ring-inversion barrier) as determined by DNMR and MM2 calculations. (3S)-Enantiomers of acetates (+)-8, (+)-10, (+)-15, and (+)-21 were preferentially formed. In the case of the acetate (-)-17 (ee 90.2%), formation of the (3R)-enantiomer was favored. C(3)—OH Group with hemiaminal-like character in rac-3 (n = 0) cannot be acetylated by any of 23 tested lipases and four esterases. For racemic alcohols 7, 9, 14, and 20, preferred acetylationof the (3S)-enantiomers, present in solution in absolute (M)-conformation, was established; only in prochiral diol 16 (n = 1) the CH2OH group in the (pro-R)-position is prevalently acetylated, presumably due to the binding to the enzyme, in absolute (P)-conformation. Temperature dependence of enantioselectivity revealed inverse correlation of the E value of rac-9, and ee values for prochiral 16, with T[K], indicating prevalent contribution of the enthalpy term to enantioselection. Absolute conformation (M/P) and absolute configuration at C(3) of all products was determined by combining CD and 1H-NMR data.

Notes: In spite of the higher reactivity of styrene with respect to ethene for the alternating copolymerization with carbon monoxide, catalyzed by chiral (dihydrooxazole)(phosphino)palladium complexes, ethene is preferentially (and randomly) enchained in terpolymerization experiments; enantioface selection for styrene is comparably high in both copolymerization and terpolymerization processes.

Notes: The successful application of the Arndt-Eistert protocol starting from commercially available N-{[(9H-fluoren-9-yl)methoxy]carbonyl}-protected (Fmoc) α-amino acids leading to enantiomerically pure N-Fmoc-protected β-amino acids in only two steps and with high yield is reported.

Notes: 8,19-Dimethyl-tetraepoxy[22]annulen(2.1.2.1): The First Tetraepoxy-Bridged Aromatic[22]AnnuleneBy McMurry reaction of 5,5′-ethylidenebis[furan-2-carbaldehyde] (15), a syn/anti mixture 16 of (E,E)- and (Z,Z)-8,19-dihydro-8,19-dimethyl-tetraepoxy[22]annulene is obtained. The (E/E)-isomers 16 are the first rotation- ally active noncyclic conjugated macrocycles, where the (E)-ethenediyl moieties rotate around the connecting single bonds. The dihydro-tetraepoxy[22]annulenes 16 are dehydrogenated by (Ph3C)BF4 as well as by O2 to give the tetraepoxy[22]annulene 11. The spectroscopic data support the character of 11 as an aromatic, diatropic ring system, which is rather sensitive towards O2. In the oxidation mixture obtained from 11, beside polymeric products, two compounds 19 and 20 can be isolated, carrying one and two CHO groups, respectively, resulting by oxidation of one or both Me-groups but having retained the aromatic 22π system of 11.

Notes: Three double-decker cyclophane receptors, (±)-2, (±)-3, and (±)-4 with 11-13-Å deep hydrophobic cavities were prepared and their steroid-binding properties investigated in aqueous and methanolic solutions. Pd°-Catalyzed cross-coupling reactions were key steps in the construction of these novel macrotricyclic structures. In the synthesis of D2-symmetrical (±)-2, the double-decker precursor (±)-7 was obtained in 14% yield by fourfold Stille coupling of equimolar amounts of bis(tributylstannyl)acetylene with dibromocyclophane 5 (Scheme 1). For the preparation of the macrotricyclic precursor (±)-15 of D2-symmetrical (±)-3, diiodocylophane 12 was dialkynylated with Me3SiC≡CH to give 13 using the Sonogashira cross-coupling reaction; subsequent alkyne deprotection yielded the diethynylated cyclophane 14, which was transformed in 42% yield into (±)-15 by Glaser-Hay macrocyclization (Scheme 2). The synthesis of the C2-symmetrical conical receptor (±)-4 was achieved via the macrotricyclic precursor (±)-25, which was prepared in 20% yield by the Hiyama cross-coupling reaction between the diiodo[6.1.6.1]paracyclophane 19 and the larger, dialkynylated cyclophane 17 (Scheme 4). Solid cholesterol was efficiently dissolved in water through complexation by (±)-2 and (±)-3, and the association constants of the formed 1:1 inclusion complexes were determined by solid-liquid extraction as Ka = 1.1 × 106 and 1.5 × 105 l mol-1, respectively (295 K) (Table 1). The steroid-binding properties of the three receptors were analyzed in detail by 1H-NMR binding titrations in CD3OD. Observed steroid-binding selectivities between the two structurally closely related cylindrical receptors (±)-2 and (±)-3 (Table 2) were explained by differences in cavity width and depth, which were revealed by computer modeling (Fig. 4). Receptor (±)-2, with two ethynediyl tethers linking the two cyclophanes, possesses a shallower cavity and, therefore, is specific for flatter steroids with a C(5)=C(6) bond, such as cholesterol. In contrast, receptor (±)-3, constructed with longer buta-1,3-diynediyl linkers, has a deeper and wider hydrophobic cavity and prefers fully saturated steroids with an aliphatic side chain, such as 5α-cholestane (Fig. 7). In the 1:1 inclusion complexes formed by the conical receptor (±)-4 (Table 3), testosterone or progesterone penetrate the binding site from the wider cavity side, and their flat A ring becomes incorporated into the narrower [6.1.6.1]paracyclophane moiety. In contrast, cholesterol penetrates (±)-4 with its hydrophobic side chain from the wider rim of the binding side. This way, the side chain is included into the narrower cavity section shaped by the smaller [6.1.6.1]paracyclophane, While the A ring protrudes with the OH group at C(3) into the solvent on the wider cavity side (Fig. 8). The molecular-recognition studies with the synthetic receptors (±)-2, (±)-3, and (±)-4 complement the X-ray investigations on biological steroid complexes in enhancing the understanding of the principles governing selective molecular recognition of steroids.

Notes: Methyl (E)-2-(acetylamino)-3-cyanoprop-2-enoate (2a), and its 2-benzoyl analog 2b ere prepared from the corresponding methyl (Z)-2-(acylamino)-3-(dimethylamino)propenoates 1 Multifunctional compounds 2 are versatile synthons for preparation of polysubstituted heterocyclic systems such as pyrroles 4, pyrimidines 5 and 6, pyridazines 7, pyrazoles 8, 9, and 11, and isoxazoles 10.

Notes: Oxy anions 3 generated from 1,2-dihydrocyclobutabenzen-1-ones 1 through addition of a charged nucleophile or from 1-hydroxy-1,2-dihydrocyclobutabenzenes 2 by deprotonation with base lead to stable products through distal and/or proximal cleavage of the strained four-membered ring via benzyl carbanion 4 and/or aryl carbanion 5. A systematic study of this process reveals the relative stability of the two isomeric carbanions 4 and 5 as a key factor in determining the course of the ring-cleavage reaction. While benzyl carbanions 4 can be trapped with carbon electrophiles, attempts at trapping aryl carbanions 5 with electrophiles other than H+ failed. In protic solvents, the magnesium salt of the tertiary alcohol 2 shows an increased rate of proximal cleavage as compared to its alkali salts. From this, we conclude that, in contrast to benzyl carbanions 4, free aryl carbanions 5 are of transient existence only. Proximal C,C-bond cleavage seems to occur either through protonation of 5 from a fast, reversible equilibrium 3⇌5 in which 3 strongly predominates, or in protic solvents possibly even through a rate-limiting protonation of 3 at the aromatic C-atom, bypassing free anion 5 altogether. Thus, additional factors other than just the relative stability of isomeric carbanions 4 and 5 are of importance in determining the regiochemistry of the base-induced C,C-bond cleavage in ketones 1 and in alcohols 2.

Notes: The decomposition of diazo ester 2b with chiral RhII catalysts proceeded via intramolecular aromatic carbenoid insertion to the racemic pyrrole derivative 5b in 72% yield. In contrast, the benzoylated precursor 16 afforded no ketorolac 1b when exposed to RhII. Methyl 2-diazo-4-phenylbutyrate (19), in turn, reacted, by 1,2-hydrogen migration rather than by aromatic substitution, to 20.

Notes: In this study, we compared the lipophilicity of O-glucuronides and their aglycones. Distribution coefficients (log D) and P values of neutral species (log P) were determined by centrifugal partition chromatography (CPC) in octanol/buffer systems. Two-phase potentiometry was also used to measure the log P value of some lipophilic solutes. The experimentally determined global influence of glucuronidation on lipophilicity, obtained as the difference (decrement) log P(glucuronide) - log P(aglycone), was found to be -1.30 ± 0.16 (n = 4) for glucuronides of alcohols (methyl, menthyl, neomenthyl, and chloramphenicol O-glucuronide). The mean decrement was -2.06 ± 0.31 (n = 9) for glucuronides of phenols (phenyl, p-nitrophenyl, 1-naphthyl, 6-bromo-2-naphthyl, 4-methylumbelliferyl, 3-coumarinyl, phenolphthalein, 4′-benzophenonyl O-glucuronide, and diflunisal phenolic glucuronide). For the acylglucuronide of diflunisal and its rearrangement isomers, the mean decrement was -1.80 ± 0.08 (n = 4; range -1.7 to -1.9). Differences in through-bond proximity effects as parametrized in the CLOGP algorithm seem to account for much of this difference. Conformational factors may also play a role, although it appears modest and unassessable for the glucuronides investigated here. The results imply that in vivo glucuronidation should have a stronger influence on the excretion of phenols than on that of alcohols.

Notes: To check if the strong inhibition of N-acetyl-β-D-glucosaminidase by the tetrazole 8 and the imidazoles 9 and 10 correlates with the presence of a heteroatom corresponding to the glycosidic O-atom, we prepared the GlcNAc-derived pyrroles (tetrahydroindolizines) 18, 19, 27, 28, 34, and 35, lacking such a heteroatom. For this. the glucose-derived pyrroles 11-13 were treated with a Lewis acid in the presence of trimethylsilyl azide. Conditions of kinetic control favored the formation of the gluco-azides 14, 23, and 30, while thermodynamic control favoured the manno-azides 20, 29, and 36. Reduction of the azides 14, 20, 23, 30, and 36 by Pd/C-catalyzed hydrogenolysis or, better, with propanedithiol and Et3N, followed by acetylation or trifluoroacetylation and hydrogenolytic debenzylation, gave the deprotected acetamido- and trifluoroacetamido-pyrroles 18, 19, 22, 27, 28, 34, 35 40, and 41. As compared to the tetrazole 8 and the imidazole 9, the pyrroles 18, 19, 27, 28, 34, and 35 are only modest inhibitors of N-acetyl-β-D-glucosaminidase from bovine kidney (Ki values between 10 and 75 μM). indicating the necessity of a heteroatom at the glycosidic position. Ki Values between 100 and 160 μM for the inhibition of N-acetyl-β-D-glucosaminidase from jack beans were determined for the pyrroles 19, 34, and 35. The trifluoroacetamides inhibited both enzymes about twice as strongly as the corresponding acetamides.

Notes: Pirlindole is an antidepressant drug. It acts principally as reversible inhibitor of monoamine oxidase-A (RIMA) and appears relatively potent in comparison with reference drugs. Pirlindole possesses stereogenic center but is generally used as racemate. In this work, the first preparative resolution of its enantiomeric couple is described. Whereas selective crystallization of salts of chiral acid failed, two asymmetric synthetic pathways were also examined; however, without success. Finally separation and isolation of enantiomers of pirlindole was completed by using the derivatization method coupled with preparative HPLC. Optical purity of each isomer was determined by chiral HPLC. The specific rotation of each antipode was also determined.

Notes: The synthesis of new ‘bridged’ β-cyclodextrin (β-CD) ‘dimers’ 7-12 was successfully achieved by two one-pot reactions from β-CD (3) and 6A-azido-6A-deoxy-β-CD (4). The ‘phosphine imine’ reaction was shown to be a superior approach compared to the Mitsunobu reaction as coupling strategy for the preparation of these ‘dimers’. NMR Data, along with molecular-modelling calculations, suggest a ‘helical-like’ arrangement for the phenanthroline-diyl-linked ‘dimer’ derivative 9. Complexation properties of 9 were established by UV-VIS-spectrophotometric titration toward four metals. Among them CuII or EuIII ions were complexed selectively by 9, but no complexation occurred with LaIII and ZnII. In addition a specific and interesting esterase activity toward the phosphodiester bond of bis(4-nitrophenyl) phosphate anion was found in the case of the CuII complex of 9.

Notes: Three new derivatives of vitamin B12 with a pyrrole head group attached to the corrin ring have been prepared. Ligand-exchange reactions and reduction provided reactive CoIII and CoII complexes. Their electro-chemical properties and their potential for fixation at the surface of electrodes by electropolymerization were studied.

Notes: The kinetics of isomerization of deuterium and hydrogen oxoperoxonitrate, ONOOD and ONOOH, respectively, to trioxonitrate(1-), NO3-, and a deuteron or proton have been studied. Analysis of the pH-rate profiles result in a normal equilibrium isotope effect (KH/KD) of 3.3. The kinetic deuterium isotope effect for the isomerization reaction is 1.6 ± 0.2 between 5 and 55°. The activation enthalpies of isomerization of ONOOD and ONOOH are identical within the error of the measurement, 86.2 ± 0.5 and 86.5 ± 0.5 kJmol-1, respectively. A secondary kinetic isotope effect of 1.6 is compatible with a mechanism of isomerization where the terminal peroxide O-atom shifts to the N-atom.

Notes: The acid-catalyzed hydrolysis of (3S,5R,6S,3′S,5′R)-5,6-epoxycapsanthin (5) led to (3S,5R,6R,3′S,5′R)-(7) and (3S,5R,6S,3′S,5′R)-capsokarpoxanthin (8). In addition, (3S,5R,8R,3′S,5′R)- (9), (3S,5R,8S,3′S,5′R)-capsochrome (10), and (3S,5R,6R,3′S,5′R)-3,6-epoxycapsanthin (6) afforded (3S,5S,6R,3′S,5′R)-capsokarpoxanthin (12) (3S,5S,8S,3′S,5′R)- (13) and (3S,5S,8R,3′S,5′S)-capsochrome (14) as well as (3S,5S,6R,3′S,5′R)-3,6-epoxyepicapsanthin (15). Compounds 5-15 were isolated in crystalline form and characterized by their UV/VIS, CD, 1H- and 13C-NMR, and mass spectra.

Notes: Blood-protein adducts are used as dosimeter for modifications of macromolecules in the target organs where the disease develops. The functional groups of cysteine, tyrosine, serine, lysine, tryptophan, histidine and N-terminal amino acids are potential reaction sites for isocyanates. Especially the N-terminal amino acids, valine and aspartic acid of hemoglobin and albumin, respectively, are reactive towards electrophilic xenobiotics. To develop methods for the quantification of such blood-protein adducts, we treated 4-chlorophenyl isocyanate (1) with the tripeptide L-valyl-glycyl-glycine (2a) and with single amino acids yielding N-[(4-chlorophenyl)carbamoyl]valyl-glycyl-glycine (3a), N-[(4-chlorophenyl)carbamoyl]valine (3b), N-[(4-chlorophenyl)carbamoyl]aspartic acid (3c), N-(4-chlorophenyl)carbamoyl glutamic acid (3d), N-acetyl-S-[(4-chlorophenyl)carbamoyl]cysteine (3e), and N-acetyl-O-[(4-chlorophenyl)carbamoyl]serine (3f), Nα-acetyl-Nε-[(4-chlorophenyl)carbamoyl]lysine (3g). For several chemicals, it was shown that blood-protein adducts are good dosimeters of exposure and dosimeters for the target dose. The hydrolysis of the N-terminal adducts of isocyanates release hydantoins which can be separated from the rest of the protein and analyzed using GC/MS or HPLC. This was achieved with 3a. The released hydantoin could be analyzed using GC/MS. We propose to analyze the N-terminal adducts of isocyanates with blood protein to distinguish between arenamine and arylisocyanate exposure.

Notes: The synthesis of 3H-naphtho[2,1-b]pyrans 9-21 linked to a thiophene moiety is described. Two different synthetic approaches were applied to prepare these novel functionalized compounds, and their spectrokinetic properties in solution are reported.

Notes: The synthesis of oligonucleotides containing 2′-deoxy-5-methylisocytidine and 2′-deoxyisoguanosine using phosphoramidite chemistry in solid-phase oligonucleotide synthesis is described. Supporting previous observations, the N,N-diisobutylformamidine moiety was found to be a far superior protecting group than N-benzoyl for 2′-deoxy-5-methylisocytidine. 2′-Deoxy-N2-[(diisobutylamino)methylidene]-5′-(4,4′-dimethoxytityl)-5-methylisocytidine 3′-(2-cyanoethyl diisopropylphosphoramidite) (1c) incorporated multiple consecutive residues during a standard automated synthesis protocol with a coupling efficiency 〉 99% according to dimethoxytrityl release. Extending coupling times of the standard protocol to ≥ 600s using 2′-deoxy-N6-[(diisobutylamino)methylidene]-5′-O-(dimethoxytrityl)-O2-(diphenylcarbamoyl)isoguanosine, 3′-(2-cyanoethyl diisopropylphosphoramidite) (7e) led to successful incorporation of multiple consecutive 2′-deoxyisoguanosine bases with a coupling efficiency 〉 97% according to dimethoxytrityl release.

Notes: Studies towards the synthesis of a chiral primary α-phosphinoalkanamine 1a are reported. O-Activated. N-carbamate-protected phenylalaninol 3a did not undergo SN reaction with KPPh2: instead, after N-deprotonation, intramolecular substitution led to formation of the aziridine derivative 5a (Scheme 2). N-Phthalimido-protected, O-activated phenylalaninol 3b also underwent an intramolecular process on treatment with KPPh2, i.e., an unusual aryl-acyliminium cyclization furnishing the (epoxymethano)isoindolo[1,2-a]isoquinolinone 7 (Scheme 3). In a reaction with KPPh2, the N,N-dibenzyl-protected and activated phenylalaninol 3d finally yielded the intermolecular SN reaction product 2a (Scheme 4). However, debenzylation by catalytic hydrogenation turned out to be impossible.

Notes: Selective NMR decoupling and nuclear Overhauser effect (NOE) experiments with phycocyanobilin (PCB) show proton-proton interactions between the terminal rings A and D, viz. the chiral C(2) methine center and the ethyl substituent at C(18), as a result of the helical conformation of this open-chain tetrapyrrole in solution. Quantitative NOE measurements and a combination of force-field and semiempirical calculations (FSC) afford inter-proton distances across the helical gap of 4.2-4.6 (NOE) and 3.2-4.2 A° (FSC). The NOE and FSC, in conjuction with a qualitative evaluation of the steric interactions in the two optimized helices, suggest furthermore that, in solution, the helix M is somewhat more stable than P. The coexistence of at least two diastereoisomers is corroborated also by the circular dichroism (CD) spectra of PCB in MeOH/EtOH which point to a temperature-dependent equilibrium in solution, and by a considerable increase of this CD upon changing the solvent from the achiral alcohols to ethyl (-)-(S)-lactate which reflects a selective solvent-induced CD differentiating between diastereoisomers.

Notes: Enantiomerically pure β-amino-acid derivatives with the side chains of Ala, Val, and Leu in the 2- or 3-position (β2- and β3-amino acids, resp.), as well as with substituents in both the 2- and 3-positions (β2,3-amino acids, of like-configuration) have been prepared (compounds 8-17) and incorporated (by stepwise synthesis and fragment coupling, intermediates 24-34) into β-hexa-, β-hepta-, and β-dodecapeptides (1-17). The new and some of the previously prepared β-peptides (35-39) showed NH/ND exchange rates (in MeOH at room temperature) with τ1/2 values of up to 60 days, unrivalled by short chain α-peptides. All β-peptides 1-7 were designed to be able to attain the previously described 31-helical structure (Figs. 1 and 2). CD Measurements (Fig. 4), indicating a new secondary structure of certain β-peptides constructed of β2- and β3-amino acids, were confirmed by detailed NMR solution-structure analyses: a β2-heptapeptide (2c) and a β2,3-hexapeptide (7c) have the 31-helical structure (Figs. 6 and 7), while to a β2/β3-hexapeptide (4) with alternating substitution pattern H-(β2-Xaa-β3-Xaa)3-OH a novel, unusual helical structure (in (D5)pyridine, Fig. 8; and in CD3OH, Figs. 9 and 10) was assigned, with a central ten-membered and two terminal twelve-membered H-bonded rings, and with C=O and N—H bonds pointing alternatively up and down along the axis of the helix (Fig. 11). Thus, for the first time, two types of β-peptide turns have been identified in solution. Hydrophobic interactions of and hindrance to solvent accessibility by the aliphatic side chains are discussed as possible factors influencing the relative stability of the two types of helices.

Notes: Tetraepoxy[22]annulene(2.2.2.0): a Tetraepoxy-Bridged Neutral Aromatic [22]Annulene of a New TypeWe describe the synthesis of tetraepoxy[22]annulene(2.2.2.0) 4, the first aromatic annulene of type B by a cyclizing twofold Wittig reaction of 2,2′-bifuran-5,5′-dicarbaldehyde (5) and the bis[phosphonium] salt 8. The configuration of 4, mainly determined by NMR spectroscopy is (Z,E,Z). According to the UV/VIS spectrum and the 1H-NMR data, the electronic situation in 4 is quite different from that of tetraepoxy[22]annulene(3.0.3.0) 2 and tetraepoxy[22]annulene(2.1.2.1) 3. According to variable-temperature 1H-NMR spectroscopy, 4 is a highly dynamic system, where the (E)-double bond rotates around the adjacent σ-bonds. At ca. -130°, this dynamic process is frozen, and 4 appears as a diatropic aromatic system; the free activation energy of the rotation ΔG≠ is ca. 8.75 kcal/mol.

Notes: In the center of the immune system, there are major histocompatibility (MHC) protein/nonapeptide complexes which are recognized by T cell. The nonapeptides consist of three regions, an N-terminal one containing three amino-acid residues with a mandatory arginine in position 2, a C-terminal one with a lysine or arginine in position 9, and a central, variable one of five residues (cf. Fig. 1). We have now synthesized the first conjugates (1-4) of oligopeptides with oligo[(R)-3-hydroxybutanoates] (OHB) as analogs of MHC-binding peptides. Of the approaches chosen (Scheme 1), a fragment coupling of a hydroxy-butanoyl-amido ester (17 and 19) with an [(aminoalkanoyl)oxy]butanoyl chloride (27; Scheme 3), followed by two peptide-coupling steps (Scheme 4), turned out to be most efficient. The conjugates H-Gln-Arg-Leu-(HB)3,4-Lys-OH (1 and 2) and H-Ala-Arg-Leu-(HB)3,4-Lys-OH (3 and 4) were thus obtained in pure form. The conjugates 1 and 2 with N-terminal glutamine have a tendency to undergo cyclization with formation of a pyroglutamate residue (ef. Fig. 2). CD Measurements at different temperatures and so-called epitope-stabilization assays show that the complexes of the conjugates 2 and 4, containing four HB units, with the HLA-B27 class-I-MHC protein are more stable than those of a model nonapeptide (C50 values of 2.25 and 1.60 μM vs. 10 μM), while the conjugates 1 and 3 with three HB units incorporated form less stable complexes (C50 values of 30 and 21 μM). The tetra(hydroxybutanoate)-peptide conjugates 2 and 4 are the first nonapeptide analogs for which the modification of the central part leads to increased affinities for a class-I-MHC protein, as compared to a model nonapeptide.

Notes: 6-Epikarpoxanthin ((all-E,3S,5R,6S,3′R)-5,-6-dihydro-β,β-carotene-3,5,6,3′-tetrol, 5), 5,6-diepikarpoxanthin ((all-E,3S,5S,6S,3′R)-5,6-β,β-carotene-3,5,6,3′-tetrol, 13), 5,6-diepilatoxanthin ((all-E,3S,5S,6S,3′S5′R,6′S)-5,6′-epoxy-5,6,5′,6′-tetrahydro-β,β-carotene-3,5,6,3′-tetrol, 14), and 5,6-diepicapsokarpoxanthin ((all-E,3S,5S,6S,3′S,5′R)-5,6-dihydro-3,5,6,3′-tetrahydroxy-β,κ-caroten-6′-one, 15) were isolated from red spice paprika (Capsicum annuum var. longum) and characterized by their UV/VIS, CD, 1H- and 13C-NMR, and mass spectra. Our investigations demonstrate that the configuration of the 3,5,6-trihydroxy-5,6-dihydro-β-end group may differ depending on the biological source.

Notes: The X-ray analyses of (η3-allyl){4-benzyl-2-[2-(diphenylphosphino-κP)phenyl]-4,5-dihydro-4-4-methyloxazole-κN}palladium(II) hexafluorophosphate (5) and the analogous [Pd(η3-1,3-diphenylallyl)] complex 6 are presented. A comparison with the (η3-allyl)- and (η-1,3-diphenylallyl)palladium complexes 2 and 3, respectively, containing the 4-monosubstituted 4,5-dihydro-2-(phosphinoaryl)oxazole ligand 1a reveals important structural differences (Fig. 3). 1H-NMR Spectroscopic investigation confirm that the 4,4-disubstituted 4,5-dihydro-2-(phosphinoaryl)oxazole ligand 4 of 5 and 6 shows the same conformation in solution as in the solid state (Table 2). The application of ligand (S)-4 in the Pd-catalyzed allylic substitution demonstrates a configurational relationship between the orientation of the allyl ligand in the intermediate (cf. complex 6) and the absolute configuration of the allylic-substitution product (Table 3).

Notes: Some new (2′-5′)triadenylates 13-16, containing at the 2′-terminal end 3′-fluoro-2′,3′-dideoxyadenosine derivatives, have been synthesized by the phosphotriester method. The selectively blocked nucleosides 2, 4, 5, and 7, were synthesized from the corresponding unprotected nucleosides 1, 3, and 6. The synthesized trimers 13, and 14 were 4- and 8-fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the natural trimer 17. In comparison to trimer 17 the new compounds 13-15 inhibit HIV-1 reverse transcriptase (RT) activity, and 15 and 16 the HIV-1 induced syncytia formation 2-3 fold whereas none of 13-16 can improve R Nase L activity.

Notes: The first asymmetric α-alkylations of lithiated sulfonamides bearing the chirality information within the amine moiety under high asymmetric inductions (de 83-95%) are described. Racemization-free acidic hydrolysis led to the title compounds 11 in acceptable overall yields and with high enantiomeric purity (ee 91- ≥ 98%; Scheme 2). As a novel chiral auxiliary, the primary amine (S,S)-or (R,R)-2 was synthesized employing the classical Erlenmeyer phenylserine synthesis (Scheme 1).

Notes: This theoretical study focuses on two indole derivatives, melatonin (1) and carvedilol (8), with the objective of improving our understanding of the molecular mechanisms underlying their radical-scavenging activity. Quantum-mechanical calculations were carried out using the AM1 semi-empirical method, some results being confirmed by ab initio (3-21G) calculations. The quantum-chemical descriptor Δ Hox (relative adiabatic oxidation potential) and the shape of the SOMO (singly occupied molecular orbital) indicate that the stabilization of its radical cation can partially explain the well-documented antioxidant efficacy of melatonin. This stablization may result from electrostatic interactions and from a hyperconjugative effect existing in a family of conformers of the melatonin radical cation having the side chain almost perpendicular to the plane of the aromatic rings. Furthermore, 6-hydroxymelatonin (7) appears to be a better free-radical scavenger than melatonin (1) in agreement with experimental results. According to the theoretical parameters Δ Hox and Δ Habs (relative bond dissociation enthalpy), carvedilol (8) is not a good antioxidant, in contrast to its ring-hydroxylated metabolites whose powerful antioxidant effects are explained by the formation of an oxyl radical stabilized by delocalization over the carbazole nucleus.

Notes: The reaction of α-nitro ketones to the corresponding α-hydroxy ketones under basic aqueous conditions, a novel transformation, was studied. The investigation revealed that the reaction is only possible with α-nitro ketones that are CH-acidic in the α′-position and readily deprotonated under the reaction conditions. The NO2/OH exchange was established to proceed with retention of configuration at the stereogenic center, and labeling experiments have shown that the OH O-atom originates, to a great extent, from the solvent. In particular, the stereochemical course of the reaction and the incorporation of external nucleophiles led us to propose a mechanism that involves neighboring-group participation. The product formation is explained by a double SN2 reaction, which proceeds via a Favorskii-like cyclopropanone intermediate.

Notes: We report on the synthesis of a receptor 4 for β,β-carotene (1), and on the binding interaction between the two which yields inclusion complex 5. The cyclodextrin ‘dimer’ 4 was obtained via condensation of the corresponding 4,4′-(porphyrin-5,15-diyl)bis phenol 8 with 6A-deoxy-6A-iodo-β-cyclodextrin (6) in the presence of Cs2CO3. Fluorescence studies of the binding interaction between ‘dimer’ 4 and β,β-carotene (1) gave a binding constant Ka of (2.4 ± 0.1) · 106 M-1.

Notes: The lithium enolate of (±)-6-endo-chloro-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-one (16) added to furan-2-carboxaldehyde giving a single aldol 19 (Schemes 1 and 2) that was converted with high stereoselectivity into (±)-(1RS,3SR,4SR,5RS,6SR)-5-exo-{(RS)-[(tert-butyl)dimethylsilyloxy](furan-2-yl)methyl}-6-endo-(methoxymethoxy)-2-oxo-7-oxabicyclo[2.2.1]hept-3-exo-yl 4-bromobenzenesulfonate (46). Highly regioselective Baeyer-Villiger oxidation of 46 provided the corresponding β-DL-altrofuranurono-6,1-lactone 49, the methanolysis of which gave (±)-methyl 1,5-anhydro-3-{(SR)-[(tert-butyl)dimethylsiloxy](furan-2-yl)methyl}-3-deoxy-2-O-(methoxymethyl)-α-DL-galactofuranuronate (51). Reduction of 51 followed by protection furnished (±)-1,4-anhydro-3-{(SR)-[(tert-butyl)dimethylsilyoxy](furan-2-yl)methyl}-3-deoxy-2,6-bis-O-(methoxymethyl)-α-DL-galactopyranose (54). Clean oxidation of the furan unit in (54). Clean oxidation of the furan unit in 54 was possible with dimethyldioxirane, giving the corresponding (Z)-4-oxoenal 59 that was converted into pyrroles such as (±)-1,4-anhydro-3-{(SR)-[(tert-butyl)dimethylsilyloxy](1-benzyl-1 H-pyrrol-2-yl)methyl}-3-deoxy-2,6-bis-O-(methoxymethyl)-α-DL-galactopyranose (58; Scheme 5), or into pyrrolidin-3,4-diols by dihydroxylation of (±)-1,4-anhydro-3-{(1′RS,2′RS,Z)-1′-[(tert-butyl)-dimethylsilyloxy]-2′,5′-bis[(methylsulfonyl)oxy]pent-3′-enyl}-3-deoxy-2,6-bis-O-(methoxymethyl)-α-DL-galactopyranose (70; Schemes 6 and 7). After adequate protection (→ 70), selective displacement of one of the mesylate moieties with LiN3, followed by hydrogenation of the corresponding primary azide and intramolecular substitution, led to four protected, stereoisomeric C-linked imino disaccharides (Scheme 7); the latter were deprotected under acidic conditions to give (±)-3-deoxy-3-[(1′SR)-2′,5′-dideoxy-2′,5′-imino-α-LD-ribitol-1′-C-yl]-DL-galactose (3), (±)-3-deoxy-3-[(1′SR)-2′,5′-dideoxy-2′,5′-imino-α-DL-arabinitol-1′-C-yl]-DL-galactose (4), (±)-3-deoxy-3-[(1′SR)-2′,5′-dideoxy-2′,5′-imino-β-DL-ribitol-1′-C-yl]-DL-galactose (5), and (±)-3-deoxy-3-[(1′SR)-2′,5′-dideoxy-2′,5′-imino-β-DL-arabinitol-1′-C-yl]-DL-galactose (6). These unprotected C-linked imino disaccharides were more stable as ammonium chlorides in H2O. Neutralization of 4 · HCl, followed by NaBH4 reduction, gave (±)-(1RS,2SR,6SR,7RS,8RS,8aSR)-1,2,3,5,6,7,8,8a-octahydro-7-[(1SR,2SR)-1,2,3-trihydroxypropyl]indolizine-1,2,6,8-tetrol (14), a new octahydroindolizinepolyol (Scheme 8). Methyl glycosides of C-linked imino disaccharides 3-6 were also obtained, such as (±)-methyl 3-deoxy-3-[(1′SR)-2′,5′-dideoxy-2′,5′-imino-α-LD-ribitol-1′-C-yl]-β-DL-galactofuranoside (7), (±)-methyl 3-deoxy-3-[(1′SR)-2′,5′-dideoxy-2′,5′-imino-β-LD-arabinitol-1′-C-yl]-β-DL-galactofuranoside (8) and -α-DL-galactofuranoside (9), (±)-methyl 3-deoxy-3-[(1′SR)-2′,5′-dideoxy-2′,5′-imino-α-DL-arabinitol-1′-C-yl]-β-DL-galactofuranoside (11) and -α-DL-galactopyranoside (10), and (±)-methyl 3-deoxy-3-[(1′SR)-2′,5′-dideoxy-2′,5′-imino-β-DL-ribitol-1′-C-yl]-β-DL-galactofuranoside (13) and -α-DL-galactopyranoside (12). All these new C-linked imino disaccharides can be obtained in their enantiomerically pure form either starting with enantiomerically pure 7-oxabicyclo[2.2.1]heptain-2-one derivatives (‘naked sugars of the first generation’) or using the method of Johnson and Zeller applied to the racemic protected aldol 3-exo-{[(tert-butyl)dimethylsiloxy](furan-2-yl)methyl}-6-endo-chloro-5-exo-(phenylseleno)-7-oxabicyclo[2.2.1]heptan-2-one (22; see Scheme 2). The unprotected C-linked imino disaccharides 3-13 and octahydroindolzinetetrol 14 were tested for their inhibitory activity toward 25 commercially available glycohydrolases. Only compound 3 which mimics the mannopyranosyl-cation intermediate during the hydrolysis of an α-mannopyranosyl-(1 → 3)-galactose has a weak, but specific α-mannosidase inhibitory activity.

Notes: Summary The potential of large-volume PTV injection was studied for the analysis of triazine herbicides in water samples. Direct water injection and in-vial extraction were described and compared. Detection limits were between 0.01–0.02 μg L−1 and relative standard deviations were 〈9%. Both methods are suitable for the analysis of triazines at ppt-level, although in-vial extraction is favourable for water samples with relatively large amounts of matrix components.

Notes: Summary A method of extraction, purification and gas chromatographic analysis of five cholesterol oxidation products (COPs) (7β-hydroxycholesterol, 5α, 6α-epoxycholesterol, 25-hydroxycholesterol, 7-ketocholesterol and cholestane-3β, 5α, 6β-triol) has been developed. The method is aimed at the determination of COPs in meat and meat products, in particular dry sausages, where large differences in the content of cholesterol and its oxidation derivatives may occur. Linearity of response of trimethylsilyl ethers was defined. The minimum concentration tested was 2.5 μg g−1 in the injected solution. The main feature of the present work is the addition of a purification step of unsaponifiables by SPE on silica cartridges. Extraction recoveries of COP standard mixtures, performed with or without the SPE step, are evaluated. The introduction of the clean-up step results in high purity samples without further losses in the entire process.

Notes: Summary A fast, simple, and reliable method is presented for the determination of atmospheric semi-volatile organic pollutants at μg m−3 levels. The method has been used to monitor potentially carcinogenic toxic compounds to which workers are exposed in workplaces, and to measure the same compounds in outdoor air.

Notes: Summary The interaction of vinylchloride (VC) with liquid foods, such as water, olive oil and honey, was studied using the relatively new technique of Reversed-Flow Gas Chromatography (RFGC). The RFGC method permits the calculation of the VC diffusion coefficient in the liquid phase (water, oil and honey) and the determination of the partition coefficient of VC between the liquid and the carrier gas, as well as the determination of the Henry's constant of VC in the liquid food. From the variation of the above parameters with temperature, thermodynamic parameters (free and excess free energies, enthalpies, entropies and activity coefficients) were calculated for the adsorption of VC by liquid foods. These are discussed in comparison with the same parameters calculated from empirical equations or determined experimentally by other techniques.

Notes: Summary The exact definition of the compressibility correction factor,j, has been extensively discussed in recent literature. In this work, it is shown that this compressibility correction factor has several different interpretations; however, the simplest and most useful meaning involves a correction from the experimentally accessible pressure at the outlet of a column to the average pressure in the column. Also, an unconventional definition of the retention volume of a solute in terms of the sample size and the equilibrium concentration of the solute in the mobile phase is presented. This retention volume definition is presented as an alternative to the common definition ofV R as the volume of carrier gas which passes through the column in a period of time called the retention time. In this discussion, it is emphasized that the temeprature dependence of the specific retention volume is determined by the thermodynamics of the phase distribution process for the solute and not by an equation-of-state for the carrier gas. Finally, the conventional correction of the specific retention volume by a factor of 273/T c can be used to correct a volume of carrier gas to a pseudo-standard state of 273 K and the average pressure in the column; however, this corrected specific retention volume has no relation to the specific retention volume that would be experimentally obtained at this standard state temperature and pressure. compressibility correction factor, and specific retention volume, were examined with regard to the physical interpretation, exact definition and appropriate standard states to be applied to these commonly reported chromatographic parameters. Such arcane discussions are beneficial to the health of science but may lead to confusion among potential and practicing chromatographers. In order to prevent or at least help ameliorate this problem, the following discussion presents a somewhat unorthodox interpretation of the questioned terms along with a pseudo-physical explanation of the so-called retention volume which is ubiquitous throughout the chromatographic literature.

Notes: Summary A complex method was developed for the determination of chlorobenzenes in soil and groundwater samples. Samples were taken at two sites in Baranya county, where a mixture of chlorobenzene waste was deposited, causing severe contamination in the environment. Clean-up of these sites demands modern and reliable analytical methods. Several sample preparation techniques were used, such as solid phase microextraction (SPME), supercritical fluid extraction (SFE), and a recently developed thermal desorption method. The applicability of various sample preparation methods was compared by measuring recovery percentages, relative standard deviations and by investigating the matrix dependency of these values. Gas chromatography was used for quantitative determination of chlorobenzenes, using MS, IR, FID and ECD detection techniques. Detection levels were as low as 1 ppt in water, and 10 ppt in soil samples. Chlorobenzene concentration was in the range 1 ppt-1 ppm in water and 100 ppb-100 ppm in soil samples. Identification and calibration of these compounds were performed by quantitative standards. This complex analytical method can be used for rapid and precise quantitative and qualitative determination of chlorobenzenes.

Notes: Summary A technique is described for determination of the amount of bonded phase in commercial columns. It is adapted to the determination of the real nature and the thickness of a siloxane bonded film. Ten-centimeter samples of column are used. The method is tested for large-bore capillary columns. Applications to kinetic studies are suggested.

Notes: Summary Sample pretreatment is often the bottleneck of a tracelevel analytical procedure. In order to increase performance, increasing attention is therefore being devoted to combining sample pretreatment on-line with the separation technique that has to be used. In the present review, a variety of procedures in use today for sample treatment coupled on-line to capillary gas chromatography (GC) is briefly discussed. Special attention is devoted to coupled-column techniques such as SPE-GC and LC-GC (SPE, solid-phase extraction; LC, column liquid chromatography) which are topics of much current interest, also because of their frequent use in so-called hyphenated systems.

Notes: Summary Steroid metabolites have been measured by capillary gas chromatography in the urine of 38 children aged 3–6 years. The children comprised three groups: those with asthma being treated with Terbutaline (13), children with asthma but not undergoing treatment (17), and control children in hospital but free from endocrine diseases (8). There were significant (P〈0.05) differences between the amounts of steroids excreted by the different groups of children. Terbutaline therapy led to elevated levels of tetrahydrocortisone, androstenediol, 11-ketopregnanetriol and a reduced ratio of androgen to cortisol metabolites compared with those for untreated asthmatic children. We assume that Terbutaline does not have a steroid-like mechanism of action but acts by modification of the activity of several adrenocortical enzymes. We suggest a hypothesis whereby the antiasthmatic effect of Terbutaline could not only be a connected with its well-known mechanism of action, but it might be explained as a result of the modification of the production of certain glucocorticoids and androgen hormones.

Notes: Summary Poly(p-tert-butyldimethoxydipropyloxycalix[4]arene-tetramethyldisiloxane) (TBCX-TMDS) and poly(dimethoxydipropyloxycalix[4]arene-tetramethyl-disiloxane) (CX-TMDS), have been prepared and used as stationary phases for isothermal capillary gas chromatographic separations of positional isomers. Retention factors and separation factors for the isomers were measured. The isomers investigated were well-resolved on the two phases. Retention of all the solutes investigated is greater on TBCX-TMDS than on CX-TMDS, probably because of extra dispersive interactions of the solutes with thetert-butyl groups of the phase. Separation factors for closely-eluting isomer pairs are similar on the two phases. This seems to indicate either that the solutes are retained by non-inclusion processes or that if the isomer molecules do enter the cavity of the calixarene, i.e. the solute is retained by inclusion, thetert-butyl groups do not play a role in discriminating between the isomers.

Notes: Summary Low amounts of triethanolamine, collected in ORBO 53 tubes during air sampling, required the development of a very sensitive method for determination. After desorption and silylation reaction with trimethylsilyl imidazole/trimethyl chlorosilane, the derivative was analyzed by gas chromatography-mass spectrometry on an Ultra 2 silica capillary column in single ion monitoring mode (retention time: about 6 min). The method has a detection limit of 1–2 pg with a desorption efficiency of about 81%. Linearity of response was ascertained in the ranges 10–100 ng and 100–1000 ng. Short-term method validation was carried out by intra- and inter-day assays on three amounts for each reference calibration curve. All results satisfied the pre-defined acceptance criteria. In general, the whole procedure was easily performed and was appropriate for our needs. Breakthrough volume was appropriate for our needs. Breakthrough volume was determined on authentic samples and was about 40–60 L, using a flow rate of 1 L·min−1. The amounts of triethanolamine found in the samples ranged from 150 to 250 ng (about 2.5–4.2 μg·m−3).

Notes: Summary Gas chromatographic chiral separation of several chiral 2-and 3-alkanols and diols was studied both in their free hydroxyl and in their trimethylsilyl ether forms. First, the derivatization procedure was verified through the identification of the trimethylsilyl ethers formed on the basis of their mass spectra and optimized to obtain quantitative reaction. The optimized procedure was applied to the trimethylsilylation of racemic mixtures of various hydroxyl compounds. The silylation was found to be highly effective in the improvement of the separation of the individual enantiomers. The major advantages of the derivatization process can be summarized as: (i) excellent baseline separation of the enantiomers of the silyl ethers was achieved in contrast to the parent OH-containing compounds, (ii) the sensitivity of detection highly increased, (iii) the separations do not show any significant concentration dependence and finally (iv) the analysis time needed decreased significantly.

Notes: Summary A procedure is described for the (non-target) screening of hetero-atom-containing compounds in tap and waste water by correlating data obtained by gas chromatography (GC) using atomic emission (AED) and mass selective (MS) detection. Solid-phase extraction (SPE) was coupled on-line to both GC systems to enable the determination of microcontaminants at the 0.02–1 μg L−1 level in 7–50 mL of aqueous sample. The screening was limited to compounds present in at least one heteroatom-selective GC-AED trace above a predetermined concentration level. These compounds were identified by their partial formulae (AED) and the corresponding mass spectra, which were obtained from the GC-MS chromatogram via the retention index concept. The potential of the approach was demonstrated by the identification of target compounds as well as all unknowns present in tap and waste water above the predetermined threshold of 0.05 μg L−1 (tap water) or 0.5 μg L−1 (waste water).

Notes: Summary The solution of a new synthesized compound, mono-6-(1'-benzo-aza-15-crown-5)-2, 3, 6- permethyl-β-cyclodextrin, in the moderately polar polysiloxane OV-1701 was coated onto fused silica capillary column. The chromatographic characteristics including column efficiency, polarity and selectivity were studied. Excellent selectivity for the separation of enantiomers and positional isomers was obtained. The results show that the combined effect between the special caves of β-cyclodextrin and crown ether plays a significant role in the separation.

Notes: Summary This article describes a theoretical/practical study of the parameters which affect the chromatograms obtained when using a molecular diode-array spectrometer as the detector in gas chromatography. The objective is to offer some rules which permit the identification of the optimum signal/noise relation. To achieve this, we study the effect of the different parameters which affect the noise and how to reduce their impact, as well as alternatives for increasing the signal. All the options tested can be applied by correctly programming the spectrometer with BASIC programs, within reach of any use who has even a small understanding of programming. Finally, we consider the effect that the selection of the acquisition conditions may have on the chromatographic resolution. All the studies are carried out using a mixture of alcohols and phenols.

Notes: Summary The separation ofm-, p-, o- xylenes andm-, p- ethyltoluenes was studied on a packed column with 2,5% of 4-[(4-chlorobenzyl)oxy]-4′-cyanoazobenzene (CBOCA) on Chromosorb W HP 100–120 mesh. The synthesis and study of the mesomorphic behaviour of CBOCA are presented. Temperature range for the separation ofm-, p-, o- xylenes (in this order of elution) is 125–85°C, at cooling. The best separation was achieved at about 90°C. The separation temperature domain ofm-ethyltoluene fromp- ethyltoluene is 160–85°C.

Notes: Summary For improved determination of aromatic amines by gas chromatography and detection with an electron capture detector (GC-ECD) a derivatization method based on the bromination of the aromatic ring in an acetic acid medium was developed. In general, all free ortho and para-positions relative to the amino group undergo electrophilic substitution. Separation of at least 30 compounds in a single chromatographic run in 30 min is possible. With this method, 56 aromatic amines were studied and only in 6 cases were no derivatives obtained. Quantitation limits determined from calibration data are 1.2–40 μg L−1 for a 100 mL sample and an injection volume of 1 μL. Previous experiments suggest that both sample and injection volume may be increased to lower the quantitation limit.

Notes: Summary Recent work demonstrated that the combination of microwave assisted solvent extraction (MASE) and capillary gas chromatography with selective nitrogen detection (GC-NPD) is a viable approach for the efficient determination of triazine herbicides in soils. However, for soils with a high organic matter content or the injection of more concentrated extracts to obtain lower LOD's the performance of gas chromatographic analysis of uncleaned extracts is hampered. This results in both a decrease of the chromatographic response of analytes and a decrease in the life time of the column due to coextracted matrix substances. The effect of various types of soils on the chromatographic analysis of triazine herbicides was studied. It appeared that for the investigated samples with an organic matter content below 5% processing of uncleaned extracts is possible. Samples with a higher organic matter content required a cleanup step. A rapid procedure on 100 mg silica cartridges has been developed using solvents compatible with the MASE extracts and the instrumental analysis. Beside the testing with different standard soils, about 120 samples of an ongoing monitoring program involving three different types of soil (organic matter content: 3–37%) were analysed. The selected compounds atrazine, desethylatrazine, desisopropyl-atrazine and simazine could be assayed in the various soil types to a level of at least 2 μg kg−1. For soil samples with a high organic matter content (〉5%), the rapid cleanup procedure allowed the trace analysis of the triazines and considerably increased the life time of the capillary column. Recoveries at levels from 2 to 50 μg kg−1 ranged from 70 to 100% with RSDs ranging from 5.1 to 9.5%. Confirmation of positive samples was carried out by gas chromatography mass spectrometry.

Notes: Summary An unknown migration contaminant was found in a number of mineral water samples contained in beverage carton packages. This compound was isolated by a fully automatic solid phase extraction system and identified by means of GC-MS as 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) [126-86-3], which is used as a surfactant in water-based printing inks and migrates during the production of the beverage carton material into the inner polyethylene film and subsequently into the product. The determined concentrations of TMDD ranged up to more than 50 μg L−1.

Notes: Summary Solid-phase microextraction (SPME) has been combined with gas chromatography (GC) and liquid chromatography (LC) for the determination of lidocaine in human urine. A polydimethylsiloxane (PDMS) coated fibre was directly immersed into buffered urine. Extraction conditions such as time, pH, ionic strength, temperature, and agitation were optimised. The extracted lidocaine was thermally desorbed in a split/splitless injector for analysis with a GC-FID system or desorbed with liquid in a specially designed SPME-LC interface for analysis with an LC-UV system. After optimisation the method developed was evaluated and validated. Extraction yields of 22% were obtained in about 45 min. The reproducibility of the method is 〈5% (relative standard deviation). For five-times diluted urine, linear ranges were found from 5–1000 and 25–1000 ng·mL−1 for SPME-GC and SPME-LC, with detection limits of 5 ng·mL−1 for SPME-GC and 25 ng·mL−1 for SPME-LC. SPME can be used as a simple sample pretreatment method for the determination of lidocaine in urine by GC and LC.

Notes: Summary Five β-cyclodextrin derivatives, heptakis[2,6-di-O-pentyl-3-O-(4-nitrobenzyl)-β-CD (CD-I), heptakis [2,6-di-O-pentyl-3-O-(5-hexenyl)]-β-CD (CD-II), heptakis-(2, 6-di-O-cinnamyl-3-O-methyl)-β-CD (CD-III), heptakis-(2, 6-di-O-cinnamyl-3-O-acetyl)-β-CD (CD-IV) and heptakis(2, 6-di-O-cinnamyl-3-O-trifluoroacetyl)-β-CD (CD-V), were synthesized and coated on fused-silica capillary coluns. Their chromatographic characteristics were tested and compared with heptakis (2,3,6-tri-O-pentyl)-β-CD (CD-VI) and heptakis (2,6-di-O-pentyl-3-O-trifluoroacetyl)-β-CD (CD-VII). It was found that the size, polarity, and aromatic property of the substituted group at the 3-position of heptakis (2,6-di-O-pentyl)-β-cyclodextrins greatly influenced their chromatographic properties and separation ability. The introduction of aromatic group or a group containing a double-bond may bring π-π interactions between the host and guest molecules, and therefore increased the separation ability of the β-CDs for substituted benzene isomers. Introduction of cinnamyl groups in to the 2,6-3-position of β-CD has a significant effect on the chromatographic properties of the stationary phases(CD-III-CD-V).

Notes: Summary In our paper we propose a new method for the determination of heats of vaporization (ΔH vap(i)) and the Gibbs free energies of vaporization (Δμp(i)) for individually selected alkylbenzenes, chromatographed on stationary phases of low and medium polarity. The method is based on a new thermodynamic description of the Kováts retention index (I (i)) making use of Trouton's rule. In fact, we attribute physical significance to two empirical relationships, well known from the literature. We can describe thermodynamically the magnitude ofI (i) using two relations, each of them potentially useful for further determination of δH vap(i) and Δμp(i). A comparison was made of the results obtained with the use of our new approach and of those already existing in the literature attained in a completely different way. The comparison suggests that the calculated δH vap(i) and Δμp(i) values are thermodynamically acceptable and hence correct, and the data suit into the series of similar values determined on stationary phases of different polarity.

Notes: Summary Gas chromatography of polychlorinated biphenyls and chlorinated pesticides in water samples is carried out after adsorption from a 25–500 mL sample, on a cartridge containing 100 mg aminopropyl-bonded porous silica. The clean-up step in which the PCBs and chlorinated pesticides are separated in different eluates is achieved by passing 25 mL of 40% aqueous methanol through the NH2 Sep-Pak cartridge. The PCBs are desorbed with 500 μL ethylacetate, which is concentrated and analysis by GC-ECD. The average recovery, at 1 ppb is 〉97% with a standard deviation 〈2. The limits of detection are 0.1 ng μL−1 and 5 pg μL−1 respectively for Cl3-PCB and Cl8-PCB congeners. In the separation of PCBs from the chlorinated pesticides tested in this work, only the Aldrin is adsorbed for 60% with the PCBs by the NH2 Sep-Pak cartridge. The method described is rapid, simple and reproducible.

Notes: Summary Stationary phases are characterised in a multilinear retention model by retention data of a set of selected prototypical substances. Prototypical stationary phases confirm the application of prototypical substances in the retention model. For comparison, 27 stationary phases are characterized with solute descriptors of the solvation model. New adjusted substance factors are calculated for 33 selected compounds for a new characterization of GC stationary phases in the extended retention model with retention values, calculated from retention indices and b-values of the n-alkane equation. Substance dipolarityD N-factors are separated from πN, the adjusted dipolarity-polarisability. New substance factors give satisfying correlation results and new explanatory factors as phase descriptors for 27 stationary phases.

Notes: Summary Quantitation of the milk fat content in mixed fats is of interest in food analysis. It can be achieved by calculation from the butyric acid (C4) content in the mixed fat and a mean C4 content for pure milk fats. Alternatively, instead of applying a C4 mean value, the C4 content in the actual milk fat can be used if this reference sample is available. A recently improved analytical method based on gas chromatography of butyric acid methyl ester using an internal standard has been applied to determine the milk fat content in mixtures with beef tallow, lard, soybean oil, olive oil, sunflower oil, palm kernel oil and palm oil ranging from 1 to 90% milk fat content. Within the whole range of mixtures, mean absolute deviations between the determined and the actual milk fat content were below 0.5% and the maximum absolute deviation was not more than 1.0% when using the reference sample. The overall mean absolute deviation was 0.04% for milk fat contents of 1 to 10% and 0.28% for milk fat contents of 10 to 90%.

Notes: Summary A gas chromatographic method for the analysis of seventeen acids in a water/ethanol matrix is described. The diluted samples were first concentrated by solid phase extraction. Nonanoic acid was the internal standard. A good separation profile was obtained for all compounds, including the isomers: n and iso-butyric acids, n and isovaleric acids and n and iso-caproic acids. The method is fast, sensitive (20–30 μg L−1) and has a good reproducibility (4–7 %). The recovery was in the range of 94%–116% for the medium chain acids (C7-C16). This method allowed the identification of fourteen acids in caninhas and other spirits. The total acid content and the profile of the exportation type caninhas are similar to the ones obtained for several international beverages.

Notes: Summary A method is proposed for the determination of alcohols and phenols based on their derivatization to benzoates and gas chromatography-gas phase molecular absorption spectrometry. All parameters affecting the derivatization reaction, such as the solvent, basic medium, benzoyl chloride and stirring time, were optimized. Chromatographic and instrumental conditions were also studied. Finally, a calibration study was performed and the results were compared to that obtained by the direct determination of the compounds.

Notes: Summary The work presents a GC method for the determination of six organophosphorous pesticide residues in cabbage. Chopped cabbage was blended with acetone, then extracted with the mixture of n-hexane:methylene chloride (1:1). The extract was purified on a GPC column packed with BioBeads SX-3 gel. The pesticides were eluted with the mixture of methylene chloride:cyclohexane (1:1) at the flow rate of 0.5 mL min−1. After concentrating the extract was analysed by GC. Nearly 100 samples of cabbage were analysed; trace residues of dimethoate (about 0.05 ppm) were found in 10 samples. The average recoveries of the pesticides were above 80% with a relative standard deviation mostly less than 10%.

Notes: Summary A capillary gas chromatographic method is described for the determination of major plant sterols and cholesterol in edible oils and fats. In the sample preparation procedure reversed-phase, solid-phase extraction with C18 adsorbent was used to extract the unsaponifiable matter and for sample cleanup after saponification. Sterols were quantitated as their trimethylsilylether derivatives using an internal standard method (betulin). The method was validated by recovery tests and analysis of two reference materials representing vegetable oil mixture and milk fat matrices. Average recoveries of spiked cholesterol and cholesterol acetate in rapeseed oil were 103±4% (n=12) and 101±3% (n=10), respectively. The sterol values determined in the reference materials were found to be in a good agreement with their given certified or indicative values. Applied to edible oils and fats, plant sterols and cholesterol at levels〉20 mg kg−1 could be accuratively quantitated.

Notes: Summary Headspace-gas chromatography was used to determine the contents of toxic 1,4-dioxane, ethylene oxide and ethylene glycol in ethoxylated alcohols and alkylamines, and in commercial cosmetics and washing products. A Permaphase PEG capillary column was used for the determination of 1,4-dioxane and ethylene oxide and a DB-17 column for ethylene glycol determination. Dimethylformamide was used as the solvent in the determination of 1,4-dioxane and ethylene oxide, and undecanol in the case of ethylene glycol. The detection limits for ethylene oxide, 1,4-dioxane and ethylene glycol are 1,2 and 10 μg·g−1, respectively.

Notes: Summary Two new kinds of calix[4]arene derivatives, 5,11,17,23-tetra-tert-butyl-25,27-bis(isopropylcarbamoyl-methoxy)-26,28-diundecenyloxy calix[4]arene (C[4]A) and 25,27-dibutoxy-5,11,17,23-tetra-tert-butyl-26,28-diundecenyloxy calix[4]arene (C[4]B), have been synthesized for use as stationary phases in capillary gas chromatography with OV1701. These stationary phases demonstrate high column efficiencies, wide operating temperature ranges, good thermal stability and excellent selectivity for aromatic isomers, especially phenol compounds. Their inclusion properties are also discussed.

Notes: Summary A detailed statistical analysis is presented for comparing the validity of selected literature-recommended equations with the unified retention index concept for calculating the retention indexes of alkylbenzenes on UCON LB 550X and naphthalenes on polydimethylsiloxane. Comparison with literature sources shows that the unified retention index provides the smallest residual error for a set of aromatic hydrocarbons.

Notes: Summary Residual synthetic adsorbent, cross-linked polystyrene, used in drug purification has been analyzed quantitatively by Curie-point pyrolysis gas chromatography. The peaks of intact polystyrene adsorbent in the pyrogram were used as key peaks for quantitative measurement of residues of the adsorbent in vitamin B1 and streptomycin sulfate. It was shown that them-ethylstyrene orp-ethylstyrene peaks in the pyrolyzates were suitable for determination of polystyrene adsorbent content. The levels of residual adsorbent in the drugs were found to be 〈0.1 %, the value stipulated by the International Conference on Harmonization (ICH). In quantitative evaluation of an adsorbent content of 0.1 % the precision was 3.6 % and 2.7 % for vitamin B1 and streptomycin sulfate, respectively.

Notes: Summary Retention indices or five 1-alkenes, seven branched alkenes and five cycloalkenes and the corresponding epoxides were determined at two temperatures on a fused-silica capillary column coated with cyanopropyl methyl siloxane to interpret their chromatographic behaviour. The standard deviation was 0.2 index units.

Notes: Summary The development of a headspace GC method (HS-GC) to determine the safrole content in differentAsarum species from China and Europe, using eugenol as internal standard, is presented in this paper. The best results could be achieved by thermostating the samples at 100°C for 30.0 min, adding 10 μL of water to each sample. Optimum pressurisation and injection time showed to be 3.0 min and 12 s, respectively. GC separation was performed on an SE-54 column. The HS-GC results for safrole were in good agreement with those obtained by direct GC analysis of the dichloromethane (DCM) plant extracts. The investigated Asarum samples showed great deviations concerning the safrole content even within the sameAsarum species, e.g.Asarum himalaicum from Sichuan contained 0.0051% of this compound, the same species from the province of Hebei 0.53%.

Notes: Summary A method for the analysis of 10 phthalate esters in plastic toys is described. The samples are soxhlet extracted in dichloromethane and phthalate esters in the extract are analysed by GC. Detection limits of dimethyl phthalate, diethyl phthalate, dibutyl phthalate, bis(2-ethylhexyl) phthalate, di-n-octyl phathalate, di-n-nonyl phthalate, benzyl butyl phthalate and benzyl octyl phthalate were approximately 5 ppm. The detection limits of diisononyl phthalate and diisodecyl phthalate, which are mixtures of several isomers, were approximately 200ppm. Analysis of 17 plastic toys revealed that only PVC-toys contained phthalate esters. Bis(2-ethylhexyl) phthalate, diisononyl phthalate and diisodecyl phthalate in concentrations up to 40% were present in the PVC-toys.

Notes: Summary Cyanide can be extracted from whole blood samples by headspace solid-phase microextraction (SPME) with a Carbowax/divinylbenzene-coated fiber. During heating a vial of a whole blood sample containing cyanide and acetonitrile as internal standard (IS) at 50°C in the presence of Na2SO4, a Carbowax/divinylbenzene-coated SPME fiber was exposed in the headspace of the vial for 45 min to allow adsorption of cyanide and IS. The fiber needle was then injected into a capillary gas chromatography (GC) instrument equipped with nitrogen-phosphorus detection. The headspace SPME-GC with a Supel-Q PLOT fused silica capillary column gave large peaks for cyanide and IS; almost no interfering peaks appeared. Recoveries of cyanide dnd IS from human whole blood were 3.02–4.06% and 0.21%, respectively. The calibration curve for cyanide added to human blood showed excellent linearity in the range of 0.04–4.0 μg mL−1; the detection limit was about 0.02 μg mL−1. The coefficients of intra-day and inter-day variation were not greater than 7.1 and 9.2%. Good correlation (r 2=0.999) was found between the present SPME-GC method and the conventional microdiffusion colorimetric method. Data on determination of cyanide in rat blood after intraperitoneal administration are also presented.

Notes: Summary The synergistic effect is investigated in mixed gas chromatographic stationary phases containing dibenzo-18-crown-6 +MPBHpB [o-methyl-p-phenylene-bis-(p-heptoxy benzoate)], [o-methyl-p-phenylene-bis-(p-heptoxy benzoate)], with benzene/cyclohexane, cyclokexanes, phenols, alcohols and aniline derivatives as sample compounds pairs. Some of the separations reveal positive or negative synergistic effect. This effect depends on the temperature, the mixing ratio and the linear velocity of the carrier gas.

Notes: Summary A rapid and new clean-up method utilizing sulfuric acid treatment is demonstrated to identify and quantify the level of organochlorine (OC) and organophosphorus (OP) pesticide residue concentrations in herbal essential oils by gas chromatography (GC). Essential oils fortified with pesticides, that are extracted from herbs by steam distillation are partitioned with 65% acetonitrile/water(v/v) and treated with sulfuric acid at different reaction times and sulfuric acid concentrations. Optimal conditions, to avoid interference from essential oils in gas chromatographic analysis, is 17% (v/v) of a mixed phase ratio of sulfuric acid to organic solvent (hexane/ethyl ether=9∶1, v/v) and a reaction time of 30s. The response of the flame ionization detector (FID) is linear for all pesticides determined. Recovery of pesticides from fortified herbs studied are in the range of 75% to 111% (RSD, 4% to 11%) for OC, and 72% to 116% (RSD, 2% to 11%) for OP. Although sulfuric acid treatment destroys carbamate and some organophosphorus pesticides, this method has efficiently reduced matrix interference and provides a rapid, economical clean-up method with excellent linear data having low coefficients of variation for the GC analyses of BHC isomers, DDD, DDE, DDT, chlorothalonil, chloropyrifos, tetradifon, fenitrothion, malathion, and parathion in matrices of herbal essential oils.