Library

Notes: β-Cryptoxanthin (1) was acetylated and then epoxidized with monoperoxyphthalic acid. After hydrolysis, repeated chromatography, and crystallization, (3S,5R,6S)-5,6-epoxy-β-cryptoxanthin (3), (3S,5S,6R)-5,6-epoxy-β-cryptoxanthin (4), (3R,5′R,6′R)-5′,6′-epoxy-β-cryptoxanthin (5), (3S,5R,6S,5′R,6′S)-5,6:5′,6′-diepoxy-β-cryp-toxanthin (6), and (3S,5S,6R,5′S,6′R)-5,6:5′,6′-diepoxy-β-cryptoxanthin (7) were isolated as main products and characterized by their UV/VIS, CD, 1H- and 13C-NMR, and mass spectra. The comparison of the carotenoid isolated from yellow, tomato-shaped paprika (Capsicum annuum var. lycopersiciforme flavum) with 3-5 strongly supports the structure of 3 for the natural product.

Notes: The 14-membered tetraazamacrocyclic Ni2+ and Cu2+ complexes of 4 (1, 4, 8-trimethyl-11-[(2-methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), 5. (1, 4-dimethyl-8, 11-bis[2-(methylthio)ethyl]-l, 4, 8, 11-tetraazacyclotetradecane), and 7 (1, 4, 8, ll-tetrakis[2-(methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), with pne, two, and four methylthio-substituted pendant chains, respectively, and the Ni2+ complex of 6 (1, 4-dimethyl-8, 11-bis (2-methoxyethyl)-1, 4, 8, 11-tetraazacyclotetradecane), with two methoxy-substituted pendant chains, were synthesized and their chemistry studied with regard to modelling F430. Solution spectra in H2O, MeCN, and DMF indicate participation of the side chain in metal coordination when the donor group is a thioether, whereas no coordination with the metal ion is observed with the ether group. Similarly the X-ray structures of the thioether-containing compounds [Ni(5)](ClO4)2, [Cu(5)](ClO4)2, and [Cu(7)](ClO4)2 show a coordination number of 5, whereas that of [Ni(6)](ClO4)2 with ether pendant chains, shows a coordination number of 4. Cyclic voltammetry of these complexes in MeCN reveals that Ni2+ is reversibly reduced to Ni+ between -0.64 and -0.77 V vs. SCE, the potential being influenced by the nature and number of the pendant chains. At more negative potentials, the thioether is cleaved, whereby a thiol is formed; the thiol is then oxidized at ca. + 0.8 V vs. SCE, when a glassy carbon electrode is used, or at ca. 0 V vs. SCE at a dropping Hg electrode. No cleavage of the ether bond in [Ni(6)](ClO4)2 is observed under similar conditions.

Notes: The photochemical synthesis of indole derivatives starting from the indoline-2-thiones 1 is described. Irradiation of indoline-2-thiones 1 in the presence of alkenes 3 gave 2-alkyl-3H-indoles 4-7 or 2-alkylindoles 8-22 through the ring cleavage of the intermediates, spirocyclic amino-thietanes, initially derived by [2 + 2] cycloaddition of the C=S bond of 1 and the C=C bond of 3. Irradiation of 1 in the presence of trialkylamines 26 gave desulfurization products 27-32 and unexpected 3-alkylindoles 33-40. N-Acylindoline-2-thiones 11-p yielded the deacylated products, indoline-2-thiones 1a-b, and ethyl esters 43 through γ-H abstraction by the excited thioamide S-atom when irradiated in CDC13/EtOH or benzene/EtOH. Oxygen analogues 2a-d also underwent intramolecular H abstraction to give the indolin-2-ones 2e-f and ethyl esters 43 in a similar way.

Notes: Antioxidant activity guided fractionation of extracts of the aerial parts of the title plant and HPLC separation yielded a series of oxygenated long-chain alkylcatechols. Their structures were inferred by spectroscopic methods and chemical transformations to be the novel 4-[(2S,4R,6S)-4-(acetyloxy)tetrahydro-6-pentyl-2H-pyran-2-yl]benzene-1,2diol (1a), 4-[(2S,4R6S)-tetrahydro-4-hydroxy-6-pentyl-2H-pyran-2-yl]benzene-1,2-diol (1b), 4-[(3S,5S)-5-(acetyloxy)-3-hydroxydecyl]benzene-1,2-diol (2a), 4-[(3S,5S)3-(acetyloxy)-5-hydroxydecyl]benzene-1,2-diol (2b), (3S,13Z)-1-(3,4-dihydroxyphenyl)-3-hydroxydocos-13-en-5-one (3a), (Z)-1-(3,4-dihydroxyphenyl)docos-13-en-5-one (4), besides the known l-(3,4-dihydroxyphenyl)icosan-5-one (5). The absolute configurations of the optically active compounds which are structurally related to the [n]-gingerols (6) and -diols (7) were established by the high-field 1H-NMR application of Mosher's method. All compounds are in vitro potent antioxidants, inhibiting the Fe2+-catalysed autoxidation of linoleic acid in the same order of magnitude as the commercial antioxidant 2,6-di(tert-butyl)-4-methylphenol (BHT). The dose-dependent inhibitory effects on soybean-lipoxygenase are in the μmol range, that of the most effective compound (3a) in the nmol range, hence being significantly more potent than the Known anti-inflammatory and analgesic drugs indomethacin and nordihydroguaiaretic acid.

Notes: The synthesis and X-ray crystal structure of a europium macrocyctic complex 1, an important catalyst used for the sequence-specific cleavage of RNA, is reported. The role of this metal complex in facilitating phosphate transesterification is discussed.

Notes: Starting from the easily available, highly functionalized acetylenic ketories 4a-i (Scheme 1), novel 2,3,5-trisubstituted thiophenes 1a-i (Scheme 2) were synthesized in good yields using a tandem Michael-addition/intramolecular Knoevenagel-condensation strategy, featuring Cs2CO3/MgSO4 (1:2) as an efficient base to effect the cyclization. Subsequent simple one-step transformations yielded 2,3-disubstituted thiophene-5-carbaidehydes 7a-c, carboxylic-acid derivatives 8, 9, and 11, and alcohol 10 (Scheme 3). These molecules constitute interesting novel thiophene-containing building blocks, useful for the preparation of low-molecular-weight compound libraries by combinatorial and parallel-chemistry techniques.

Notes: Lanthanide picrate complexes with the ligand N,N,N′,N′-tetraphenyl-3,6-dioxaactanediamide (tdd): [Ln(Pic)3(tdd)] (Ln = La, Nd, Eu, Tb, Er) have been prepared in a nonaqueous medium and characterized by elemental analysis, conductivity measurements, IR, and 1H-NMR spectra. The crystal structures of the complexes for Ln = Nd and Er were determined. The early lanthanide, NdIII, crystallizes as the nona-coordinate complex [Nd(Pic)3(tdd)]. 2 CH3CN in the monoclinic space group P21n with a = 11.384(2), b = 18.805(4), c = 27.526(5) Å, β = 99.41(1)°, V = 5832(2) Å3, and Dc = 1.58 gcm-3 for Z = 4. The structure was refined to R = 0.0505, based on 4772 observed Deflections. The late lanthanide, ErIII, forms an octa-coordinate complex [Er(Pic)3(tdd)]; crystals are triclinic, P1, with a = 12.449(2), b = 17.065(2), c = 26.243(4) Å, α = 72.12(1), β = 87.86(1), γ = 84.60(1)°, V = 5282(1) Å3, and Dc = 1.68 g cm-3 for Z, = 4. The structure was refined to R = 0.0469, based on 10666 observed reflections, The results reveal that tdd forms a ring-like structure with its four O-atoms, coordinating to the metal ions as multidentate ligand, together with one O-atom of the bidentate picrate. The structure of the complexes is greatly affected by the ionic radius due to participation of the picrates in coordination.

Notes: Intramolecular [Pd2(dba)3]/tri(2-furyl)phosphine-catalysed (dba = dibenzylideneacetone, PhCH=CHCOCH=CHPh) cyclisations of olefinic propargylic carbonates I provided alk-1-enyl-(3-aza)bicyclo[3.1.0]-hexanes VIII in good yields. A palladium cascade sequence I → II → III → IV → VII → VIII is proposed. Furthermore, chiral propargylic carbonates such as 23, 24 and 25 allowed diastereoselective formation of bicyclo[3.1.0]hexanes 29, 30 and 31, respectively. The first diastereoselective synthesis of the monoterpene, (-)-α-thujone 40 illustrates the potential of the method.

Notes: The structure of rogioldiol A ((-)-1), isolated from the red seaweed Laurencia microcladia, was determined. Employing the exciton-coupling technique for rogioldiol A p-bromobenzoate (2), the absolute configuration at C(9) of (-)-1 was assigned, and, together with extensive NMR experiments, the absolute configuration at C(10) and preferred conformations of (-)-1 were determined. The absolute configuration of the hetero-substituted cyclohexane ring was deduced in analogy from the X-ray structure of 4, a derivative of the aldehyde 3, which was isolated from the same seaweed and is believed to be a degradation product of (-)-1.

Notes: New chromenes annulated with different six-membered azaheterocycles were prepared, i.e., the 3H-pyra-no[3,2-f]quinolines 9/10 and 14, the 8H-pyrano[2,3-h]isoquinoline 11, the 8H-pyrano[3,2-f]quinazolme 12, the 8-H-pyrano[3,2-f]quinoxaline 13, and the 2H-pyrano[2,3-f]isoquinoline 15. The synthesis was achieved using conveniently substituted α,β-unsaturated aldehydes and organotitanium intermediates arising from azaheterocyclic phenols. Their photochromic behaviour (photocolouration yield, UV/VIS spectrum of photomerocyanines, rate constant of thermal bleaching) were studied besides those of corresponding naphthopyrans. The heterocycle effect and the role of substituents in the pyran moiety were investigated quantitatively through the study of the photochromic properties and the solvent effects. Diaryl-substituted azino-fused chromenes, especially isoquinoline derivatives, exhibit increased colourabilities and bathochromically shifted spectra for photomerocyanines which open up new prospects for photochromic applications.

Notes: The 2′,3′-O-isopropylideneuridine (1) reacts with MeI in the presence of an excess of NaH in THF giving 2′,3′-O-isopropylidene-5′-O-methyluridine (2). Prolonged reaction time gives rise to 2′,3′-O-isopropylidene-3,5′-O-dimethyluridine (4). The use of an equimolar amount of base and alkylating agent results predominantly in methylation at N(3) (→ 3).

Notes: We describe a new, efficient synthesis of DX-9065a (4), a potent inhibitor of the blood coagulation enzyme factor Xa (fXa) which has previously been prepared in more than 20 steps. We saved approximately 10 steps starting with a Pd-catalyzed cyanation of the triflate 10 of 7-methoxynaphthalen-2-ol (9). After cleavage of the MeO group with boron tribromide, the triflate 6 was coupled to acrylate 5 in a Heck reaction (→3). The subsequent transformations led to DX-9065 a.

Notes: The Cu2+ and Ni2+ complexes of three reinforced tetraazamacrocycles, containing a piperazine subunit and one or two alkyl substituents at the other two N-atoms have been prepared and their structural properties studied. In solution, the Ni2+ complexes are square-planar and show no tendency to axially coordinate a solvent molecule or an N3- ion. In contrast, the Cu2+ complexes change their geometry depending upon the donor properties of the solvent, being square-planar in MeNO2 and pentacoordinate in DMF. They also easily react in aqueous solution with N3- to give ternary species with pentacoordinate geometry, the stabilities of which have been determined. In the solid state, the X-ray crystal structures of three Cu2+ complexes also show both geometrical arrangements, two having a square-planar, the other one a distorted square pyramidal geometry. The difference behavior of Ni2+ and Cu2+ stems from the fact that the structural change from square-planar to square-pyramidal can easily be accomplished for Cu2+, whereas, for Ni2+, it is accompanied by an electronic rearrangement from the low-spin to the high-spin configuration. The relatively rigid ligands cannot Adapt to the somewhat larger high-spin Ni2+ion.

Notes: N-Monosubstituted 1,3-diamines were selectively functionalized at the secondary N-atom via 2-Ph-substituted hexahydropyrimidine intermediates. Reaction of the diamines with benzaldehyde, followed by treatment with an electrophile and hydrolysis, provided the desired products with excellent selectivity and in high yields. N4,N9-bis[3-phenylprop-2-enoyl]spermine (4a), which was further converted to N1,N1 2-bis[3-phenylprop-2-enoyl]spermine (15) by a transamidation reaction, was prepared by this way in 82% yield from spermine (1). Compound 4a was alternatively synthesized in 83% yield, equally from 1, by a sequence involving intermediary protection of the terminal amino groups.

Notes: As previously shown, oligo- and poly(β-hydroxyalkanoates) have a high tendency to form lamellar crystallites with ca. 50-Å thickness which corresponds to chain lengths of 16 units (Fig. 1). To have monodisperse model compounds, we have now prepared bicyclic derivatives with three parallel (27-29) or two parallel and an antiparallel chain (68-70) consisting of up to 16 3-hydroxybutanoate (3-HB) units. We also prepared dendritic compounds (71-75, 82-85) containing oligo(3-HB) chains which cannot possibly be arranged as in the lamellae; the branching units were prepared from trimesic acid (= benzene-1,3,5-tricarboxylic acid). So far, none of the prepared samples formed crystals or contained crystalline domains which would have been suitable for single-crystal or powder-diffraction X-ray analysis. The terminally deprotected dendrimers (74, 75, and 85) are multi-anionic (up to 12 peripheral CO2H groups) and biodegradable. The macromolecular HB derivatives (molecular weight up to 10150 Da) have been fully characterized by IR, 1H- and 13C-NMR, [α]D, and elemental analysis. Especially important is the analysis by mass spectrometry with the MALDI-TOF technique (Fig. 2), proving that the products are monodisperse; application of a new variation of this MS method (post source decay = PSD or fragment analysis by structural time of flight = FASTTM) allows for the observation of metastable fragment ions and, thus, is a tool for structural oligomer analysis (Fig. 3).

Notes: 5-Methyl-1,4-naphthoquinone (1) is a remarkable probe to study hydrogen and proton transfer reactions. The photoenol 4-hydroxy-5-methylidene naphthalen-1 (5H)-one (2) is formed in the ground state within 2 ps of excitation and with a quantum yield of unity, presumably through a conical intersection of the S0 and S1 hypersurfaces. In aqueous acid, enol 2 is hydrated to 5-(hydroxymethyl)naphthalene-1,4-diol 3 (X = OH, Scheme 1). The rate of hydration of 2 increases linearly with acid concentration from ca. 1.5 × 104 s-1 at pH 6 to reach a maximum value of 9 ×107 s-1 when the remaining carbonyl function is protonated, pKa(2+) = 1.1. Contrary to an earlier suggestion, the rate-determining step in the acid-catalyzed hydration of 2 is addition of water to the conjugate acid 2+. Pronounced acceleration of the decay rate of 2 by hydrazoic-acid buffers indicates competitive trapping of 2+ by the azide ion. In neutral-to-weakly-basic solutions, enol 2 reacts by ionization, pKa(2) = 6.5, and nearly diffusion-controlled condensation of the carbanionic species 2- with quinone 1. Proto-nation at the methylidene C-atom does not compete measurably with protonation on carbonyl O-atom, despite a Substsial thermodynamic basic for carbon Portoation of ca. 50 kJ mol-1 for 2 and 100 mol-1 for 2-.

Notes: O-Alkylation of 8-hydroxy-1H-quinolin-2-one (1) afforded 8-(2-oxopropoxy)-1H-quinolin-2-one (2) which was immediately cyclized to form the tricyclic 2,3-dihydro-3-hydroxy-3-methyl-5H-pyrido[1,2,3-de][1,4]benzoxazine,-5-one (3). The Reformatsky-type condensation of 3 furnished antiplatelet 8-[(2,3,4,5-tetrahydro-2-methyl-4-methylidene-5-oxofuran-2-yl)melhoxy]-1H-quinolin-2-one (4). Its counterparts 7a-f, Ph-substituted at C(2) of the furan ring, were obtained from 1 via alkylation and the Reformatsky-type condensation. Although compound 4 was less active against platelet aggregation than 7a-f, it was the only compound which exhibited significant inhibitory activity on high-K+ medium, Ca2+-induced vasoconstriction and was more active than most of its Ph-substituted counterparts against norepinephrine-induced vasoconstrictions.

Notes: The two structurally similar 20-phenyl- and 20-(4-methoxyphenyl)-11-(nitrosooxy)pregnan-20-ol derivatives 4 and 7 behave differently under photolytic conditions, the former nitrous acid ester affording, as a main product, the benzo-fused hexacyclic compound 9, and the latter the 21-nitro derivative 12. Mechanistic aspects of these transformations are discussed.

Notes: The synthesis of a variety of potent macrocyclic growth hormone secretagogues, i.e. 5, 9, 12, and 20-22, based on the known lead structure L-692,429 (1) is described. These conformationally constrained growth hormone secretagogues were prepared by joining the two essential pharmacophores, the amino-acid side chain at the 1H-1-benzazepine moiety and the 1,1′-biphenyl moiety with a variety of linkers. The most potent analog was found to be L-744,080 (21), a derivative in which a 2′-carboxamide moiety at 1,1-biphenyl is N,O-joined to the OH group of the (2-hydroxypropyl)amino-acid side chain by a C4 ester linker. This potent analog may be useful in determining the bound conformation of the benzolactam class of growth hormone secretagogues at the newly identified GHS receptor, L-744,080 (21) with an ED50 of 20 nM was up to fifty times more potent than the seco-acid precursor and 3-fold more potent than the parent 2′-tetrazole compound L-692, 429 (1).

Notes: Addition of CH2N2 to 2,3:5,6-di-O-isopropylidene-1-thio-mannono-1,4-lactone (1) gave the 2,5-dihydro-1,3,4-thiadiazole 2 and the 4,5-dihydro-1,2,3-thiadiazole 3. First-order kinetics were observed for the thermolysis of 3 (Scheme 3) at 80-110° in C6D5Cl solution and of 2 (Scheme 3) at 20-35° in CDC13, respectively. The 1,2,3-thiadiazole 3 led to mixtures of the thiirane 9, the starting thionolactone 1, the thiono-1,5-lactone 8, and the enol ether 7, while the isomeric 1,3,4-thiadiazole 2 led to mixtures of the anomeric thiiranes 9 and 12, the O-hydrogen S,O,O-ortholactone α-D-14, the S-methyl thioester 15, the S,S,O-ortholactone 13, and the 2,3:5,6-di-Oisopropylidene-mannono-1,4-iactone (16). Pure products of the thermolysis were isolated by semipreparative supercritical fluid chromatography (SFC), whereas preparative HPLC led to partial or complete decomposition. Thus, the β-D-mannofuranosyl β-D-mannofuranoside 10, contaminated by an unknown S species, was isolated by preparative HPLC of the crude product of thermolysis of 3 at 115-120° and partially transformed in CD3OD solution into the symmetric di(α-D-mannofuranosyl) tetrasulfide 11. Its structure was evidenced by X-ray analysis. Similarly, HPLC of the thermolysis product of 2 gave the enethiol 17, the sulfide 19, and the mercapto alcohol 18 as secondary products. Thermolysis of the thiirane 9 at 110-120° (Scheme 4) led to the anomeric thiirane 12 which was transformed into mixtures of the enethiol 17 and the enol ether 7. Addition of H2O to 17 and 7 gave the corresponding hemiacetals 18 and 20. The mechanism of the thermolysis of the dihydrothiadiazoles 2 and 3, and the thiiranes 9 and 12 is discussed.

Notes: α-Substituted N-acylbornane-10, 2-sultams 6, 9, and 10 can be converted into enantiomerically pure ketones 5. 13, and 14, respectively, via a two-step procedure involving a known mercaptolysis reaction followed by an [Fe(acac)3]-mediated coupling of the resulting S-benzyl thioesters with Grignard reagents. Furthermore, enantiomerically pure aldehydes 23 can be obtained from α-substituted N-acylbornane-10,2-sultams 6 via a one-step reduction with (i-Bu)2AIH. No epimerization at the α-chiral center is observed during the cleavage reaction whereby the chiral auxiliary, bornane-10,2-sultam 1 or ent-l, was recovered. By using this methodology, several natural products or precursors thereof can be prepared.

Notes: Benzo[a]heptalene has been synthesized by two different approaches. The first one follows a pathway to hexahydrobenzo[a]heptalenone 19a that has been already described by Wenkert and Kim(Scheme). Indeed, 19a was obtained in a mixture with its double-bond-shifted isomer 19b. Reduction of this mixture to the corresponding secondary alcohols 26a/26b and elimination of H2O lead to a mixture of the tetrahydrobenzo[a]heptalenes 23a-d (Scheme7 and 8). Reaction of 23a-d with 2 equiv. of triphenylmethylium tetrafluoroborate in boiling CHCl3, followed by treatment with Me3N in CH2Cl2, generated directly 2, unfortunately in a mixture with Ph3CH that could not be separated from 2 (Scheme 10 and 11). The second approach via dimethyl benzo[a]heptalene-6,7-dicarboxylate (30) (Scheme 12) that was gradually transformed into the corresponding carbaldehydes 37 and 43 (Scheme 14) both of which, on treatment with the Wilkinson catalyst [RhCl(PPh3)3] at 130° in toluene, smoothly decarbonylated, finally gave pure 2 as an unstable orange, viscous oil. UV/VIS, NMR, and mass spectra of 2 are discussed in detail (cf. Chapt.3).

Notes: The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and i-proline alkyl esters with several nitroolefins was investigated. Cyclic and acyclic nitroolefins add to the anti form of the ylide in a highly diastereoselective but poorly regioselective manner to give pyrrolizidine derivatives. In a few cases, the stereochemical results strongly support a stepwise mechanism.

Notes: Some 2′-deoxy-1′,2′-seco-D-ribosyl (5′→3′)oligonucleotides (= 1′,2′-seco-DNA), differing from natural DNA only by a bond scission between the centers C(1′) and C(2′), were synthesized and studied in order to compare their structure properties and pairing behavior with those of corresponding natural DNA and homo-DNA oligonucleotides (2′,3′-dideoxy-β-D-glucopyranosyl oligonucleotides). Starting from (-)-D-tartaric acid, 2′-deoxy-1′,2′-secoadenosine derivative 9a and 1′,2′-secothymidine (9b) were obtained in pure crystalline form. Using the phosphoramidite variant of the phosphite-triester method, a dinucleotide monophosphate 1′,2′-seco-d(T2) was synthesized in solution, while oligonucleotides 1′,2′-seco-d[(AT)6], 1′,2′-seco-d(A10) and 1′,2′-seco-d(T10) were prepared on solid phase with either automated or manual techniques. Results of UV- and CD-spectroscopic as well as gel-electrophoretic studies indicated that neither adenine-thymine base pairing (as observed in natural DNA and homo-DNA), nor the adenine-adenine base pairing (as observed in homo-DNA) was effective in 1′,2′-seco-DNA, Furthermore, hybrid pairing was observed neither between 1′.2′-seco-DNA and natural DNA nor between 1′,2′-seco-DNA and homo-DNA.

Notes: Flavo-thiazolio-cyclophane 6 was prepared on a gram scale by an 18-step synthesis (Schemes 3 and 4). This pathway involved the very efficient preparation of bromo-cyclophane 32 (37% yield over 13-steps), which can be readily modified to create various multiply functionalized receptors. This bromide 32 was subsequently converted into the corresponding boronic acid and connected to the 7-bromoflavin 10 (Scheme 2) via Suzuki coupling to give flavo-cyclophane 36. The thiazolium unit was then introduced after quaternization of the tertiary amino groups of 36. Flavo-thiazolio-cyclophane 6, with both prosthetic groups attached in proximity to the well-defined cyclophane binding site, is a functional model for the enzyme pyruvate oxidase. In basic methanolic solution, 6 catalyzes the oxidation of aromatic aldehydes to their corresponding methyl esters. Cyclophane 6 shows saturation kinetics, and the turnover number calculated for the oxidation of naphthalene-2-carbaldehyde to methyl naphthalene-2-carboxylate (kcat = 0.22 s-1) is one of the highest reported for an artificial enzyme. Control experiments showed that the catalytic advantages of 6 result from the macrocyclic binding and reaction site as well as from the covalent attachment of both cofactors to this site. The catalytic cycle is completed by electrochemical re-oxidation of the reduced flavin moiety at a low working electrode potential (- 0.3 V vs. Ag/AgCl), and up to ca. 100 catalytic cycles can be performed on a preparative scale, The intramolecular nature of the electron transfer from the active aldehyde intermediate to the flavin is particularly conducive to the oxidation of unreactive aldehydes.

Notes: The phosphoramidites 6b and 9 as well as the phosphonate 6a derived from 7-(hex-1-ynyl)- and 7-[5-(trifluoroacetamido)pent-1-ynyl]-substituted 7-deaza-2′-deoxyguanosines 1 and 10, respectively, were prepared (Scheme 1). They were employed in solid-phase oligodeoxynucleotide synthesis of the alternating octamers d(hxy7c7G-C)4 (12), d(C-hxy7c7G)4 (13), and d(npey 7c7G-C)4 (15) as well as of other oligonucleotides (see 22-25; Table 2; hxy = hex-1-ynyl, npey = 5-aminopent-1-ynyl). The Tm values and the thermodynamic data of duplex formation were determined and correlated with the major-groove modification of the DNA fragments. A hexynyl side chain introduced into the 7-position of a 7-deazaguanine residue (see 1) was found to fit into the major groove without any protrusion. The incorporation of the (5-aminopent-1-ynyl)-modified 7-deaza-2′-deoxyguanosine 2 into single-stranded oligomers of the type 24 and 25 did not lead to change in duplex stability compared to the parent oligonucleotides. The self-complementary oligomer 15 with alternating npey7c7Gd (2) and dC units did not lead to a cooperative melting, either due to orientational disorder or interaction of the 5-aminopent-1-ynyl moiety with a base or with phosphate residues nearby or on the opposite strand.

Notes: The determination of the chemical structure of a previously unknown Maillard reaction product with an amino acid incorporated in a four-ring structure is reported. The red compounds 1a and 1b, isolated from a thermally treated aqueous solution of furan-2-carbaldehyde and L-alanine, were identified as (S)-4{(E)-1-formyl -2-(2-furyl)ethenyl}-5-(2-furyl)-2-{(E)-(2-furyl)methylidene}-2, 3-dihydro-α-methyl-3-oxo-1H-pyrrole-1-acetic acid and its 2-{(Z)-(2-furyl)methylidene}isomer, respectively, by several 1D- and 2D-NMR techniques, MS, UV, and IR spectroscopy as well as by synthetic experiments. 2D-NOESY and 2D-ROESY experiments performed for conformation analysis indicated the existence of two atropisomers.

Notes: Irradiation (λ = 350 nm) of 1H-[2]benzothiopyran-1-one (2) in the solid state affords selectively and in good yield 6aα, 6bα, 12bα, 12cα -tetrahydrocyclobuta[1, 2-c:4, 3-c′]bis([2]benzothiopyran)-5, 8-dione (3), the head-to-head (HH) cis-cisoid-cis-cyclodimer of 2, X-Ray analysis of 2 confirms that this reaction proceeds according to the well-established topochemical principles. The same dimer 3 is obtained in low yields on irradiation of 10-1 M solutions of 2 in either MeOH or MeCN, while no conversion at all is observed in benzene. On irradiation of 2 in MeCN in the presence of tetrachloroethene, the [2 + 2] photocycloadduct 4 is formed in good yield, the conversion 2 → 4 being efficiently quenched by naphthalene. In contrast, no reaction is observed -on irradiation of 2 in the presence of 2, 3-dimethylbut-2-ene, neither in polar nor in apolar solvents.

Notes: The difference in steric strain between the oxidized and the reduced forms of tetraaminecopper complexes is correlated with the corresponding reduction potentials. The experimentally determined data considered range from -0.54 to -0.04 V (vs. NHE) in aqueous solution and from -0.35 to -0.08 V (vs. NHE) in MeCN. The observed and/or computed geometries of the tetraaminecopper(II) complexes are distorted octahedral or square-pyramidal (4 + 2 or 4+1) with (distorted) square-planar CuN4 chromophores (CuII—N = 1.99-2.06 Å; Cu—O4+2Ax ≈ 2.5 Å; Cu—O4+1ax ≈ 2.3 Å), those of the tetraaminecopper(I) complexes are (distorted) tetrahedral (four-coordinate; CuI—N = 2.12-2.26 Å; tetrahedral twist angle ∅ = 30-90°). The reduction potentials of CuII/I couples with primary-amine ligands and those with macrocyclic secondary-amine ligands were correlated separately with the corresponding strain energies, leading to slopes of 70 and 61 kJ mol-1 V-1, with correlation coefficients of 0.89 and 0.91, respectively. The approximations of the model (entropy, solvation, electronic factors) and the limits of applicability are discussed in detail and in relation to other approaches to compute reduction potentials of transition-metal compounds.

Notes: The reaction of thiobenzophenone (= diphenylmethanethione; 8a) or 9H-fluorene-9-thione (8b) and methyl fumarate (9) in excess PhN3 at 80° yields a mixture of diastereoisomeric thiiranes 10 and 11 (Scheme 1). A mechanism involving the initial formation of 1-phenyl-4, 5-dihydro-1H-1, 2, 3-triazole-4, 5-dicarboxylate 12 by 1, 3-dipolar cycloaddition of PhN3 and 9 is proposed in Scheme 2. The diazo compound 13, which is in equilibrium with 12, undergoes a further 1, 3-dipolar cycloaddition with thioketones 8 to give 2, 5-dihydro-1, 3, 4-thiadiazoles 14. Elimination of N2 yields the thiocarbonyl ylide 15 which cyclizes to the corresponding thiirane. Desulfurization of the thiiranes 10 and 11 with hexamethylphosphorous triamide leads to the olefinic compounds 16 (Scheme 3). The crystal structures of 10a, 11a, and 16b were determined.

Notes: β-Hexapeptides 1-5 and a β-dodecapeptide 6 with sequences containing two different types of β-amino acids (aliphatic proteinageous side chains in the 2- or in the 3-position) have been prepared. CD (Fig. 1) and NMR measurements indicate that, with one exception, the secondary structures formed by these new β-peptides differ from those of isomers studied previously. Detailed NMR analysis of the β-hexapeptide 5 (with alternating β2,β3-building blocks) and molecular-dynamics simulations have produced a minimum energy conformation (Fig. 2,b)which might be described as a novel irregular helix containing ten- and twelve-membered H-bonded rings. This demonstrates the great structural variability of β-peptides, since three different helical secondary structures have been discovered to date.

Notes: Catalytic control of regio-, diastereo-, and enantioselectivity in the 1,3-dipolar cycloaddition of 3-acryl-oyloxazolidin-2-one (4) with different nitrones 2 by the application of a [TiX2(TADDOLato)] complex as the catalyst was developed (TADDOL = α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanol). In the absence of a catalyst, the 1,3-dipolar cycloaddition of 4 with 2 proceeded to give a mixture of regioisomers, whereas, in the presence of a catalyst, the regioselectivity of the reaction could be controlled. Three asymmetric [TiX2(TADDOLato)] catalysts were tested, and it was found that use of the [Ti(OTs)2(TADDOLato)] complex gave complete regioselectivity, high ‘endo’-selectivities (〉 90% d.e.), and enantioselectivities corresponding to 48-70% e.e.

Notes: A systematic investigation of the rotational behavior of aryl substituents in α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs) is presented. In the use as chiral ligands for enantioselective metal-catalyzed reactions, a change from phenyl to bulkier substituents, e.g., 1-naphthyl, gives rise to an astounding alteration of the selectivity, The possible existence of preferred rotamers of TADDOLs has so far not been given due attention, which encouraged us to look at the validity of the Knowles model, originally formulated for diaryl substituted bisphosphines. 1H-NMR Investigations at various temperatures as well as X-ray powder diffraction were employed to study the rotation in the case of tetra(1-naphthyl) TADDOL 1. To support the interpretation of the experimental results, molecular mechanics, semiempirical, and ab initio calculations were performed. For comparison, the energy surface of tetraphenyl TADDOL 2 was calculated as well. Our results lead to the conclusion that for 1, only one major conformation is present in both solution and solid state, which determines the stereochemical outcome of the catalyzed reactions.

Notes: Synthesis of Triafulvalene Precursors by ‘Carbene-Dimerization’ of 1-Halogeno-1-lithiocyclopropanesBi(cyclopropylidenes) 7a, 7c, and 7e are available in a simple one-pot reaction by treating 1,1-dibromocyclo-propanes 5 at -95° with BuLi and CuCl2. Attempts towards triafulvalene precursors with good leaving groups are reported. The most promising attempt makes use of 2,2′-bis(phenylthio)-3,3′-bis(trimethylsilyl)-1,1′-bi(cyclopropylidene) (7c) which has been oxidized to give the bis(phenylsulfonyl) derivative 7g. So far, F--induced elimination experiments with 7g failed.

Notes: Preparation of 2-biarylcarbaldehydes using an intramolecular free-radical ispo-substitution is described. The two aryl moieties to be coupled are pre-associated using a glycolamide derivative. An unusual amidomethyl leaving group was successfully employed in this process.

Notes: The synthesis and X-ray analysis of a racemic dilithiated S-ethyl-N-methyl-S-phenylsulfoximine cluster 2 with N,N,N′,N′-tetramethylethane-1,2-diamine (TMEDA) as coordinating solvent is presented. The lithium complex 2 consists of a mixed tetrameric mono- and dilithio salt. Unexpectedly, a separation of the enantiomers in mono-and dilithiated antipodes with respect to the chirality center on the S-atom is observed. Dilithiation of S-ethyl-N-methyl-S-phenylsulfoximine (1) affords a chiral dinucleophile which undergoes highly regie- and stereoselective alkylation reactions with bis-electrophiles.

Notes: Hetero- or homocoupling of protected 1,4-cis-diethynylated 1,5-anhydroglucitols leads to two isomeric cyclotrimers and to four isomeric cyclotetramers. The C3-symmetric cyciotrimer 31, the C4-symmetric cyclotetramer 35, and the D2-symmetric cyclotetramer 6 have been prepared before. We have now synthesized the C1-symmetric cyciotrimer 13, and the C1- and the C2-symmetric cyclotetramers 22 and 27, respectively. The cyclotrimer 13 was prepared by intramolecular, oxidative homocoupling and, alternatively, by a one-pot trimerization/cyclization of the monomer 36 (Schemes 1 and 5, resp.). Oxidative homocoupling was used for the cyclization of the tetramers 19 and 25, leading to 22 and 27. The tetramer 19 was made by sequential Cadiot-Chod-kiewicz coupling (Scheme 2)and the tetramer 25 by a combination of a Cadiot-Chodkiewicz reaction and an intermolecular, oxidalive homocoupling (Scheme 3). The acetates 34 and 38, corresponding to 35 and 27, respectively, were also made by a one-pot dimerization/cyclization of the dimer 37 (Scheme 5). Intramolecular oxidative heterocoupling is also feasible and results in an alternative, more convenient synthesis of the acetylated cyclotrimer 30 and the acetylated cyclotetramer 34 (corresponding to 31 and 35, resp.; Scheme 4). The solid-state conformation of the C4-symmetric cyclotetramer 34 corresponds well to the one predicted by force-field calculations. We compared the water-solubilities of the cyclotrimers 13 and 31 and the tetramers 6, 22, 27, and 35, their calculated conformations (MM3*), and the D-adenosine binding properties of the cyclotetramers 6, 27, and 35.

Notes: X-Ray crystal structure of 4-(methylthio)-4-nitro-1-(pyrrolidin-1-yl)buta-1,3-diene (2b)The C-atoms of the butadiene chain have been numbered as shown in 1 and 2. These numbers have been retained throughout the discussion for the sake of clarity and consistency. indicates the presence of a C—H…S hydrogen bond. This might also explain the observed downfield shift of this proton in solution.

Notes: An approach to a new class of cyclic hydroxamic acids is described leading to a formal combination of a benzoxazine subunit related to some natural aglucones occurring in plants with the steroidal skeleton from two members of the estra-1,3,5(10)-triene series. The annelation procedure for a 4-hydroxy-1,4-oxazine moiety to the aromatic A-ring in estrone (1) and 1-hydroxy-4-methylestra-1,3,5(10)-trien-17-one (7), used as steroidal precursors, proceeds in four or three steps, respectively (Schemes 1 and 2, resp.). First, a 2-nitro group is introduced regioselectively by a novel nitrosation-oxidation procedure or by conventional nitration (→ nitrophenols 2 and 8). Reaction of the phenolic unit of 2 and 8 with methyl bromoacetate or ethyl chlorooxoacetate gives rise to the nitro esters 3, 4, 9, and 10, which are subjected to reductive cyclization either by means of Zn dust in ammonium chloride solution (for the acetates) or of H2/Pt(S)/C (for the sensitive oxalates). Hence, the novel cyclic hydroxamic acids 5, 6, 11, and 12 of the estra-1,3,5(10)-triene series are obtained.

Notes: The synthesis of the tricyclo-deoxynucleoside analogs 1 and 2 and of the corresponding cyanoethyl phosphoramidite building blocks 16 and 21 for oligonucleotide synthesis is described. These tricyclic deoxynucleoside analogs differ from the recently introduced bicyclo-deoxynucleosides by an additional cyclopropane unit joined to the centers C(5′) and C(6′) of the latter (se Fig. 1), and thus represent a further member of the class of nucleoside analogs with constraint conformational flexibility. The synthesis of the tricyclo-deoxynucleoside was achieved by a diastereoselective carbene addition to the enantiomerically pure silyl enol either 8/9 and a Vorbrüggen condensation of the tricyclic carbohydrate unit 10/11 with in situ persilylated thymine and N6-benzoyladenine. Selective tritylation of the tertiary OH—C(5′) and phosphinylation of OH—C(3′) of 1 and 2 afforded the corresponding phosphoramidites 16 and 21. The ‘exo’-configuration of the newly introduced cyclopropane ring was confirmed by 1H-NMR-NOE spectroscoy. The α-D- and β-D-configuration at C(1′) of the nucleoside analogs 1 and 14 (2 and 19, resp.) was assigned by 1H-NMR-NOE spectroscopy and NOESY. Modeling studies of the β-D-anomeric nucleoside analog 1 indicate a preference for the 2′-endo-conformation of the furanose ring and a partial correction of the torsion angle γ to the anti-clinal range compared to bicyclo-deoxynucleosides.

Notes: The hydroxo complex (Bu4N)2[Ni2(C6F5)4(μ-OH)2]reacts with 2,3,4,5,6-pentafluoro benzenamine (C6F5-NH2), 1,3-diaryltriaz-1-enes (ArNH—N=N—Ar, Ar = Ph, 4-MeC6H4, 4-MeOC6H4), 7-aza-1H-indole (= 1H-pyrrolo[2.3-b]pyridine; Hazind), N-phenylpyridin-2-amine(pyNHPh), and N-phenylpyridine-2-carboxamide (py-CONHPh) at room temperature in acetone to give the binuclear complexes (Bu4N)2[Ni2(C6F5)4(μ-C6F5NH)2] (1) and (Bu4N)2[{Ni(C6F5)2} 2(μ-OH)(μ-azind)] (2) and the mononuclear complexes Bu4N[Ni(C6F5)2(ArN3Ar)] (3-5), Bu4N[Ni(C6F5)2(pyNPh)] (6), and Bu4N[Ni(C6F5)2(pyCONPh)] (7). The hydroxo.complex (Bu4N)2[{Ni(C6F5)2-(μ-OH)}2] promotes the nucleophilic addition of water to pyridine-2-carbonitrile, 2-aminoacetonitrile, and 2-(dimethylamino)acetonitrile, and complexes 8-10 containing pyridine-2-carboxamidato, 2-aminoacetamidato and 2-(dimethylamino)acetamidato ligands are formed. Analytical (C, H, N) and spectroscopic (IR, 1H and 19F-NMR, and FAB-MS) data were used for structural assignments. A single-crystal X-ray diffraction study of (Bu4N)2[{Ni(C6F5)2}2(μ-OH)(μ-azind)] (2) established the binuclear nature of the anion; the two Ni-atoms are bridged by an OH group and a 7-aza-7H-indol-7-yl group, but the central Ni—O—Ni—N—C—N ring is not planar, the dihedral angle between the Ni—O—Ni and Ni—N—C—N—Ni planes being 84.4°.

Notes: Two simple thiols derived from the parent TADDOL, α,α,α′,α′ tetraphenyl-2,2-dimethyl-1,3-clioxolan-4,5-dimethanol, are used to prepare Cu1 complexes C and D to catalyze (0.05 equiv.) 1,4-additions of Grignard reagents RMgCl to cyclic enones with enantioselectivities which are comparable to or better than previously reported (enantiomer ratios up to 92:8).

Notes: It has been found that dimethyl heptalene-4,5-dicarboxylates, when treated with 4 mol-equiv. of lithiated N,N-dialkylamino methyl sulfones or methyl phenyl sulfone, followed by 4 mol-equiv. of BuLi in THF in the temperature range of -78 to 20°, give rise to the formation of 3-[(N,N-dialkylamino)sulfonyl]- or 3-(phenylsul-fonyl)benzo[a]heptalene-2,4-diols of. (cf. Scheme 4, and Tables 2 and 3). Accompanying products are 2,4-bis{[(N,N-dialkylamino)sulfonyl]methyl}- or 2,4-bis[(phenylsulfonyl)methyl]-4,10a-dihydro-3H-heptaleno[1,10-bc]furan-3-carboxylates as mixtures of diastereoisomers of. cf. Scheme 4, and (Tables 2 and 3) which are the result of a Michael addition reaction of the lithiated methyl sulfones at C(3) of the heptalene-4,5-dicarboxylates, followed by (sulfonyl)methylation of the methoxycarbonyl group at C(5) and cyclization of. (cf. Scheme 5). It is assumed that the benzo[a]heptalene formation is due to (sulfonyl)methylation of both methoxycarbonyl groups of the heptalene-4,5-dicarboxylates of. (cf. Schemes 6 and 8). The resulting bis-enolates 35 are deprotonated further. The thus formed tris-anions 36 can then cyclize to corresponding tris-anions 37 of cyclopenta[d]heptalenes which, after loss of N,N-dialkylamido sulfite or phenyl sulfinate, undergo a ring-enlargement reaction by 1,2-C migration finally leading to the observed benzo[a]heptalenes of. (cf. Schemes 8 and 9). The structures of the new product types have been finally established by X-ray crystal-structure analyses (cf. Figs. 1 and 2 as well as Exper. Part).

Notes: A comprehensive series of multiple adducts of C60 was prepared by tether-directed remote functionalization. When the tether-reactive-group conjugates 2 and 10 were attached to methano[60]fullerenecarboxylic acid ( = cyclopropafullerene-C60-Ih-carboxylic acid) and C60, respectively, the e-bis-adducts 4 and 9 (Schemes 1 and 2) were obtained with complete regioselectivity as predicted by semi-empirical PM3 calculations (Fig. 2). Attachment of the anchor-tether-reactive-group conjugate 13 to C60 by Bingel reaction, followed by double intramolecular Diels-Alder cycloaddition afforded the tris-adduct 12 (Scheme 3). Starting from 12, a series of selective e-additions led to the tetrakis-adducts 16 and 19 (Scheme 4), pentakis-adducts 20-23 (Scheme 5), and, ultimately, to hexakis-adducts 24 and 25 (Scheme 6), and 29 and 30 (Scheme 7) with a pseudo-octahedral addition pattern on the fullerene core. Oxidative cyclization of diethynylmethanofullerene 30 under Eglinton-Glaser conditions afforded the trimeric and tetrameric acetylenic macrocycles 26, with three, and 27, with four appended C60 moieties, respectively (Scheme 8). These multinanometer-sized compounds are the first soluble derivatives of C195 and C260, two members of a new class of fullerene-acetylene hybrid C-allotropes with the general formula Cn(60 + 5). The matrix-assisted laser-desorption time-of-flight mass spectra of 26 and 27 showed a remarkable fragmentation; the sequential loss of fullerene spheres led to the formation of ions corresponding to mono-fullerene adducts of the cyclocarbons cyclo-C15 and cyclo-C20 (Fig. 4). Large solvent effects were observed in the Bingel addition of 2-bromomalonates to higher adducts of C60, with the use of polar solvents enhancing the reaction rate without loss of regioselectivity. Experimental evidence for the enhanced reactivity of eface over eedge bonds was obtained, which had previously been predicted in computational studies. The correlated series of mono- to hexakis-adducts of C60 allowed identification of the changes in reactivity and physical properties that occur, when the conjugated π-electron chromophore of the fullerene is reduced as a result of increasing functionalization; this analysis is the subject of the directly following paper.

Notes: The 3-alkyl-2,2-dimethyl-4-(tert-butyl)-2H-thietes 9a-c were obtained in several steps from the corresponding, newly synthesized, 3-alkyl-2-(tert-butyl)thiophenes 5a-c. Irradiation (254nm) of these tetraalkylated four membered S-heterocycles leads to a photostationary equilibrium with enethiones 10a-c (thiete/enethione 3:1).

Notes: Electron Transfer and Ion-Pair Formation: Titrations of Tetracyanoethene by Alkaline and Alkaline Earth Metals in Aprotic SolutionFor alkaline and earth alkaline metal ‘titrations’ of the π-acceptor tetracyanoethene in aprotic (c(H⊕) 〈 0.1 ppm) solution, UV/VIS and ESR spectra have been measured in a sealed glas apparatus. Isosbestic points prove uniform but differing metal-mirror reduction processes for [Li]x, [Na]x, and [K]x vs. [Cs]x. The formation of solvent-shared or solvent-separated contact ion pairs detected is supported by subsequent crystallization and structure determination. For the tetracyanoethene radical anion, semiempirical PM3 calculations with limited configuration interaction allow to reproduce the structural data as well as the long-wavelength charge transfer excitation.

Notes: Interactions in Crystals: The Dimorphism of (2-Pyridyl)(2-pyrimidyl)aminePreceding structural studies of 2-aminopyridine derivatives prove that they form polymorphic H-pair-bonded dimmers, and, therefore, (2-pyrimidyl)amine has been crystallized under different conditions. Two different monoclinic modifications are characterized by their crystal structures of the same space group P21/c: form I exhibits the well known herringbone motif and form II the sandwich-herringbone one. Both modifications contain almost identical planar, H-pair-bridged molecular dimmers. Crystals of form I are readily obtained from any solvent, whereas those of form II result either on fast evaporation of a Et2O solution or by resolidification of the melt. Differential thermal analysis (DTA) and crystallization experiments at different temperatures prove, for both modifications, no transitions in the temperature range between -25° and the melting point at 152° and, therefore the system should be monotropic. The structural and thermodynamic aspects of the (2-pyridyl)(2-pyrimidyl)amine dimorphism are discussed in comparison to those of the trimorphism observed for di(2-pyridyl)amine.

Notes: Interaction in Crystals: The Keyboard of Na⊕ Coordination Numbers in Its Carbazole Anion SaltsSome local minima in the shallow potential of the system carbazole anion, sodium cation, and the ethers tetrahydrofuran, 1,2-dimethoxyethane, diglyme, triglyme, tetraglyme, 15-crown-5 as well as 2.2.1-cryptand are explored experimentally and by quantum-chemical calculations. Three prototype contact-ion multiples of Na⊕-solvated carbazole anion M⊖ salts have been crystallized and structurally characterized: polyether-solvated monomers [M⊖Na⊕solv]1, solvent-shared dimers [M⊖Na⊕solv]2, and solvent-separated polyions [(M⊖)nNa⊖solv](n-1)- [Na⊕solv](n-1). The Na⊕ coordination numbers stretch from 3 to 7 as illustrated by the compounds [(M-)3Na+]⊖⊖[Na+(2.2.1-crytand)]2 for 3 and 7, [(M-)2Na+(THF)2]⊖ [Na⊕(2.2.1-cryptand)] for 4 and 7, [M- Na+(diglyme)]2 for 5, or [M- Na+(l 5-crown-5)] for 6. Structural comparison is based on literature analogies as well as on results of MNDO calculations concerning charge distribution and enthalpies of formation. Taken together, the results demonstrate the delicate energy balance, by which cation solvation can influence the formation of organic salts.

Notes: Alkylation of 3-oxo-1,2-thiazetidine 1,1-dioxide 2 yields the N-alkylated 3-oxo-β-sultams 3a-i. Solvolysis with NaOH or NH3 selectively opens the N—S bond forming the sulfonate carboxamides 4 and the sulfonamidocarboxamides 7, respectively. Furthermore, the hitherto unknown compounds of type 5 are prepared, representing a strained four-membered ring with a diacylated, sulfonated N-atom. Depending upon the reaction conditions, 3b-d and 3g are rearranged by base-catalyzed reactions into the substituted 4-oxothiazolidine 1,1-dioxides 9 or 10. Structures are elucidated by spectroscopic methods, established by crystal-structure analyses, and a possible way of formation is proposed. Furthermore, some side reactions and transformations are reported.

Notes: Synthesis of (3-Aminopropyl)arylsilanes, Including One or Two Heterocyclic Patterns, Potential FungicidesFlusilazole is an effective silylated fungicide used on a large scale for plant protection. We synthesized several flusilazole analogs and also copied the tebuconazole design, an other very efficient fungicide, which has four atoms between the aromatic group and the heterocyclic moiety. In contrast to flusilazole, we obtained dissymetric structures around the Si-atom by using successively two different Grignard reagents. In another way, the 1H-1,2,4-triazole moiety was exchanged in several cases by other N-heterocycles such as 1H-imidazole, piperidine, and 2,6-dimethylmorpholine, already present in other fungicidal compounds. Finally, several compounds having two N-heterocycles of the same or different nature were prepared.

Notes: The 2,2-disubstituted 2H-azirin-3-amines 7 (2,2-disubstituted 3-amino-2H-azirines) were used as amino-acid synthons in the preparation of medium-sized cyclic depsipeptides and peptides derived from salicylic acids 6 and anthranilic acid 19, respectively (Schemes 2--4 and 5, resp.). The combination of the ‘azirine/oxazolone method’ for the synthesis of linear peptides containing α,α-disubstituted α-amino acids and the acid-catalyzed amide cyclization in DMF at 60° proved to be an excellent preparative route to ten-membered cyclic depsipeptides and peptides. In the case of the anthranilic-acid derivative, a transannular ring-closure reaction was observed (24 → 25). Larger rings proved to be extremely sensitive to hydrolysis.

Notes: Second derivatives of the UV spectra of 2-(4-alkoxybenzyl)cyclopentan-1-ols and their acetates were used for the quantitative analysis of reaction kinetics of enzyme-mediated hydrolytic process. To determine the enantiomeric purity of the products using non-chiral HPLC columns, their diastereoisomeric esters of 3,3,3-trifluoro-2-methoxy-2-phenylpropanoic acid(MTPA) were prepared. The absolute configuration of the products was established using a combination of the results of a HPLC analysis and 1H/19F-NMR measurements of the diastereoisomeric MTP esters. The analytical method described consists of an easy routine HPLC analysis which can sometimes be used as a quick on-line analysis of the reaction kinetics and as a quick stepwise analysis of the optical purity and the absolute configuration of the products.

Notes: The partial synthesis of 10,22-dihydro-4,5-dioxo-4,5-secopheophorbide a (1) from pheophorbide a methyl ester (2) is described. A regioselective, photooxygenolytic reaction of (pheophorbidato a methyl ester)cadmium(II)(3) provides the entry to the crucial 4,5-secoporphinoid structure in form of the (10,22-dihydro-4,5-dioxo-4,5-seco-pheophorbidato a methyl ester)cadmium(II) (4). The hydride reduction of this 4,5-dioxo-4,5-secophytoporphyrin ester occurs selectively at the ‘eastern’ meso-position to lead (after demetallation) to 10,22-dihydro-4,5-dioxo-4,5-secopheophorbide a methyl ester (5). This oxobilin-carbaldehyde has the structure assigned earlier to an ester of an isolation form of the red pigment(s) from Chlorella protothecoides. Hydrolysis of the propanoate ester function of 5, selectively catalyzed by pig liver esterase, then yields the title compound 1. The red tetrapyrrole 1 may represent an intermediary chlorophyll catabolite in degreening plants.

Notes: Treatment of celery leaves (Apium graveolens, cv. secalinum) with Jasmonic acid (JA, 1) or analogues of amino-acid conjugates of Jasmonic acid such as the leucine conjugate with 1-oxoindan-4-carboxylic acid (IN-ILE, 2) stimulated the biosynthesis of the furanocoumarins psoralen (6), xanthotoxin (8), bergapten (7), and isopimpinellin (9). Besides the increase of the compounds within the leaf, a significant amount (ca. 20%) of the total furanocoumarins was deposited on the surface of the leaf. The two monomethoxy furanocoumarins, 7 and 8, began to increase steadily and simultaneously within the leaf and on the leaf surface ca. 40 h after the onset of the jasmonic-acid stimulus. Within the leaf, the ratio 7/8 was ca. 1.3:1.0, while among the surface lipids 8 dominated (7/8 0.8:1.0), indicating that the export of the compounds to the surface is not a simple diffusive translocation along the oil-ducts. Females of the carrot fly (Diptera, Psilidae) responded with an increased oviposition to the altered leaf surface chemistry of the JA-treated celery plants. The effect shown for total leaves was corroborated by surrogate leaves treated with leaf-surface extracts of JA-induced leaves. Based on the known stimulation of oviposition by furanocoumarins, we conclude that the enhanced amount of furanocoumarins on the surface can explain the insects' preference for the JA-stimulated plants. This is the first report of a JA-induced change of the surface chemistry of a plant and an increase of the acceptability of treated leaves for a specialist insect, like the carrot fly.

Notes: The stepwise palladium-catalyzed coupling of dibromo-1,6-methano[10]annulene derivatives to a phenyl-acetylene substituted by an electron-withdrawing group followed by coupling with a phenylacetylene possessing an electron-donating group allows the preparation of donor/acceptor systems which contain three aromatic moieties linked by ethynediyl bridges. The same type of cross-coupling starting from 2-ethynyl-1,6-methano[10]annulene and bromo-substituted azobenzene derivatives provides easy access to a new class of azo dyes. The properties of these compounds are compared to those of analogous compounds containing only benzene rings.

Notes: The title alkaloids were prepared from the common chiral precursor (-)-(2S)-2-phenyl-1, 5, 9-triazacy-clotridecan-4-one (4) which we had synthesized earlier. The spectral data for the spermidine macrocycles are in good agreement with the data reported for the isolated samples. Our experimental results indicate that the originally reported [α]D value of -2.6 (c = 0.10, MeOH) for natural (S)-viburnine is erroneous and should be + 17.0 (c = 0.92, MeOH). As a result of the chiroptical study conducted, it can be shown empirically that all alkaloids of the ‘celacinnine’ type have the (S)-configuration.

Notes: The two conformers of a cyclohexa-2, 4-dienone with different substituents at C(6) on irradiation are believed to undergo ring opening stereospecifically affording a mixture of two configurationally isomeric diene-ketenes (and descendents thereof)- Exceptions are generally found for those dienones with one C and one O substituent or even with two C substituents, if one of them carries a polar group at a site able to interact through space with the ring C=O group. In these cases, only one of the two anticipated diene-ketenes (and descendents thereof) is produced. A thorough investigation of the photochemistry of a series of structurally different cyclohexa-2, 4-dienones on analytical as well as on preparative scale extends our mechanistic knowledge of the various routes from diene-ketenes into a variety of compound classes. Novel compound classes accessible to diene-ketenes are seven-membered carbocycles (by intramolecular aldolization of the zwitterion of appropriately substituted, transiently formed diene-(N, O)-ketene acetals) and β-lactams (by Staudinger reaction).

Notes: Khusimone (1), one of the main odor-donating compounds of vetiver oil, is subject of the following study on structure/odor relationship. Ring opening of the carbonyl-functionalized bridge of the tricyclic khusimone leads to the bicyclic structures 2a/b. The enantioselective approach to these degraded structures is described, and the olfactory consequences are studied. Starting point of the synthesis is an enantiomerically pure enone ester which is easily obtainable from camphorsulfonic acid.

Notes: Replication (single-turnover) of pyranosyl-RNA (= p-RNA) sequences can be accomplished reliably by template-directed ligation of 2′, 3′-cyclophosphates of short oligomers. The ligation process was studied using (mostly) octamers as templates and tetramers as ligands. The transcription of the sequence pr(GGGCGGGC) into the (antiparallel) complementary sequence pr(GCCCGCCC) by ligation of two molecules of pr(GCCC)-2′, 3′-cp was investigated in detail; In aqueous 1.5M LiCI solution of pH 8.5 at room temperature (0.45 mM ligand, 0.15 m,M template), the reaction proceeds in up to 60% yield within a week. It is limited by concomitant hydrolysis of cyclophosphate groups of both reactand and ligation product as the only efficient side reaction, the latter occurring ca. three times more slowly than ligation. No ligation at all is observed in the absence of template. The reaction is highly regioselective: the (4′ → 2′) phosphodiester junction is formed exclusively; no isomeric (4′ → 3′) junctions are found. For ligation to occur, template and ligand must be homochiral and must have the same sense of chirality; with chiro-diastereoisomeric tetramer-2′, 3′-cyclophosphates containing a single enantio-ribopyra-nosyl unit, no ligation is observed, except to a minor extent in the case of the diastereoisomer that has that unit at the 4′-end. Observations made in experiments involving six different octamer templates containing isomeric base sequences indicate that the ligation process does not tolerate a mismatch at ligation sites. However, ligation still takes place when a mismatch occurs at either end of the (octamer) template. Ligation efficiencies differ widely, depending on the nature, as well as the sequence, of participating bases. These differences can be understood qualitatively by considering the relative stability of ternary pre-ligation complexes, together with the differences in interstrand base stacking at ligation sites, Dominance of the latter over intrastrand base stacking is the feature of the p-RNA structure that appears to determine most of the characteristic properties of p-RNA.As regards the etiological context of our work on nucleic-acid alternatives, it is essential that the chemical properties found for p-RNA be compared with the corresponding properties of RNA. In the RNA series, the two ligations of the replicative cycle r(GGGCGGGC) ↔ r(GCCCGCCC) using the corresponding ribofuranosyl-te-tramer 2′, 3′-cyclophosphates as ligands are found to proceed also, though somewhat less efficiently than in the p-RNA series; however, the ligation step produces exclusively the unnatural (5′ → 2′) phosphodiester junctions instead of the natural (5′→ 3′) junctions. This is in sharp contrast to p-RNA, where template-controlled 2′, 3′-cyclophosphate ligations produce the ‘correct’ phosphodiester junctions.

Notes: 1-(2′-Deoxy-2′-fluororibofuranosyl)pyrimidines were synthesized and incorporated into an RNA oligonucleotide to give 5′-r[CfGCf(UfUfCfG)GCfG]-3′ (Cf: short form of Cd2′f2′ = 2′-deoxy-2′-fluorocytidine; Uf: short form of Ud2′f2′ = 2′-deoxy-2′-fluorouridine). The oligomer was investigated by means of UV, CD, and NMR spectroscopy to address the question of how F-labels can substitute 13C-labels in the ribose ring. Through-space (NOE) and through-bond (scalar couplings) experiments were performed that make use of the ameliorated chemical-shift dispersion induced by 19F as an alternative heteronucleus. A comparison of the structures of fluorinated vs. unmodified oligomer is given. It turns out that the fluorinated oligonucleotide exists in a 14:3 equilibrium between a hairpin and a duplex conformation, in contrast to the unmodified oligonucleotide which predominantly adopts the hairpin conformation. Furthermore, the fluorinated hairpin structure adopts two distinct conformations that differ in the sugar conformation of the Uf5 and Cf6 nucleoside units, as detected by the 19F-NMR chemical shifts. The role of the 2′-OH group as stabilizing element in RNA secondary structure is discussed.

Notes: Non-racemic, planar chiral 1, 2-disubstituted [Cr(η6-arene)(CO)3] complexes were obtained via external chiral ligand-controlled nucleophilic addition of alkyl-, vinyl-, and aryllithium reagents to monosubstituted complexes followed by an endo-hydride abstraction with trityl cation. The reactions with [Cr(CO)3(η6-phenyloxazoline)], [Cr(CO)3(η6-phenylmethaneimine)], and [Cr(CO)3 (η6-phenylmethanenydrazone)] took place with complete ortho-selectivity and a high degree of enantioselectivity (up to 98% ee).

Notes: A First Example of a Porphyrinoid Fulvalene: Synthesis, Structure, ESR and Electrochemical InvestigationsThe macrocyclic tetraepoxy-1H-[21]annulen-1-one 4 can by synthesized by the cyclizing Wittig reaction of 5,5′-carbonylbis[furan-2-carboxaldehyde] (11) and the bisphosphonium salt 12, obtained from 2,2′-bifuran-5,5′-dicarboxaldehyde (13). According to an X-ray structure analysis, the annulenone 4 is not planar in the crystal; the 1H-NMR spectra of 4 reveal an averaged planarity with respect to the NMR timescale. The McMurry reaction of 4 yields fulvalene 3 in 43% yield as the most expanded fulvalene hithertoo known. The X-ray structure analyses of 3 surprising establishes a ‘syn’-orientation of the two rings with respect to the central C=C bond, thus forming a basket-like molecule. The 1H-NMR spectrum confirms the averaged planarity of both macrocycles in 3. CV and spectroelectrochemical measurements of 3 suggest a reversible two-electron reduction producing dianion 15 with two aromatic, anionic 5a,15a-didehydro-10H-21,22,23,24-tetraoxa-5a,15a-dihomocorrole (= tetraoxa[22]porphyrin(2.1.2.0)) ring systems containing 22π electrons each. The formation of 15 can also be achieved chemically by reaction of 3 with metallic potassium. The dication 16 of 3 may be antiaromatic, but the exact electronic structure is dubious. ESR and ENDOR investigations on the radical cation and the radical anion of 3 indicate that the free electron is delocalized in the entire molecule.

Notes: Four novel glycosides, bambusicolasides III-VI (1-4), were isolated from the aphid Pseudoregma bambusicola T. The structures of 1-4 were elucidated by spectral evidence including FAB-MS and C.H-COSY, HMBC, and NOE difference experiments, and by hydrolysis. In vitro tests with these compounds showed little cytotoxic activity against human KB cells (〈 10%).

Notes: Anomalous variations of one-bond C—C scalar coupling constants are observed in going from trinorbornane-to trinorbornene-like structures. Most notably, a 10-Hz increase is observed in the coupling constant involving the C-atoms of the ethano branch facing the C=C bond. An effect of about half the size is characteristic of higher homologues (bicyclo[2.2.2]octenes), but no such effect is observed for monocyclic molecules.

Notes: Syntheses of New Phosphono Analogues of Pantetheine DerivativesThe phosphono analogues 5 and 13 of pantothenate 4′-(dibenzyl phosphate) and pantetheine 4′-(dibenzyl phosphate), respectively, are prepared as intermediates for the synthesis of a coenzyme-A phosphono analogue (Schemes 1 and 2). The synthesis of phosphono analogues 20 and 21 of oxapantetheine, which are structurally similar compounds to the phosphono analogue of pantetheine, is also described (Scheme 3).

Notes: The syntheses of benzo-fused benzo[2, 1-b:3, 4-b′]dithiophenes 1 and benzo[2, 1-b:3, 4-b′:5, 6-c″]trithiophenes 2 are described. The treatment of easily available 3, 3′-bis(phenylethynyl)-2, 2′-bithiophene derivatives 5a and 6 (via PdII-catalyzed alkynylation of the corresponding 3, 3′-dibromo-2, 2′-bithiophenes; see Scheme 1) with chlorotris-(triphenylphosphine)rhodium(I) yields the corresponding cyclic rhodium complexes 7 (Scheme 2) which smoothly react with acetylenes and sulfur to give 1 and 2 in good yields (Schemes 3-5).

Notes: The treatment of bromo-substituted 1,6-methano[10]annulenes with sodium thiolates in DMF provides easy access to alkylthio- and arylthio-substituted 1,6-methano[10]annulenes (Schemes 2-4). These compounds are then brominated with N-bromosuccinimide (NBS) to study their reactivity in electrophilic substitution reactions (Schemes 5 and 6). The resulting brominated thio-1,6-methano[10]annulenes are, in a subsequent reaction, subjected to Heck coupling with (4-nitrophenyl)acetylene (13) to produce the alkynylated derivatives 14 in reasonable yield (Scheme 7).

Notes: Comparative semi-empirical PM3 and ab initio STO 3-21G calculations on bornanesultam-derived dienophiles containing the structural moiety SO2—N—C(O)—X(α) = Y(β) suggest that, among the conformers of low energy, the thermodynamically less stable SO2/C(O)-syn,C(O)/X=Y-s-cis conformation is also reactive in terms of LUMO level and atomic coefficients. Furthermore, the X(α), Y(β) LUMO atomic coefficients are nonequivalent with respect to both X(α)-re and X(α)-si faces, and thus have, depending on the conformation, a matching or mismatching stereoelectronic influence with the co-operative steric effect. This dissymmetry is believed to result from the generalized anemone effect of the N lone pair, itself anomerically stabilized and directed, in the absence of crucial steric interactions, by the pseudo-axial anti-periplanar S=O bond. Five N-acyl-substituted bornanesultams arc discussed ((-)-1a: N-acryloyl, X=CH, Y=CH2; (-)-1b; N-crotonoyl, X=CH, Y=CHMe; (-)-1c: N-N′-fumaroyl, X=CH, Y=CH(C(O)-bornanesultam); 2a: N-glyoxyloyl, X=CH, Y=O; 2b: N-acylnitroso, X=N, Y=O). In this context, differences with toluenesultams 3 are pointed out. A previous report on N-(acylnitroso)-bornanesultam 2b is revisited, and the diastereoselectivity observed is shown to result from thermodynamic control.

Notes: Ring Opening of Sterically Crowded Spirocyclic 2, 5-Dihydro-l, 3, 4-thiadiazoles by Cycloaliphatic Secondary AminesAt room temperature, the spirocyclic 2, 5-dihydro-l, 3, 4-thiadiazole 3 reacted with cyclic secondary amines 6 via ring opening to give N-alkylidene-hydrazones of type 7 (Scheme 2). A reaction mechanism via a base-catalyzed transformation of the dihydrothiadiazole ring to the corresponding thiolate 19 and the intermediate thioaldehyde 21 is proposed in Scheme 6. An analogous reaction occurred with the mixture of the dispiro compounds 4/5 and morpholine (6a) or azetidine (6d), leading to a mixture of isomeric dihydrazones 8 and 9 (Scheme 3). The structure of the symmetrical isomer 8a was established by X-ray crystallography. In addition to 8a and 9a, the thiirane lOa (Scheme 3) was isolated as a minor product.

Notes: The synthesis of novel TbIII labels suitable for protein labelling are reported. Their luminescence properties as antibody conjugates were measured and compared to the results of corresponding TbIII chelates of the parent ligand structures. When the lowest triplet-state energy level of the parent donor ligand was over 23000 cm-1, i.e., the energy gap between the 5D4 level of TbIII and the lowest triplet-state energy level of the ligand exceeded 2600 cm-1, the label derivative with a long decay time (τ = 1.35-2.93 ms) and a high luminescence yield (ε. Φ = 3770-4560) was found to be suitable for bioaffinity assays.

Notes: This work describes a straightforward synthesis of two 3′-(β-D-glycopyranosyloxy)flavylium ions thought to be good models of natural anthocyanins (pigments). For both pigments and for the non-glycosylated flavylium ion taken as a reference, H2O addition and proton-transfer reactions as well as formation of molecular complexes with chlorogenic acid and caffeine (copigmentation) are quantitatively investigated in mildly acidic aqueous solution. A remarkable affinity of caffeine for the trans-chalcone form of the pigments is demonstrated. Moreover, the differences in the flavylium pKa values are interpreted in terms of possible intramolecular H-bonding between the glycosyl residue and the chromophore. The discussion is then extended to a series of malonylated anthocyanins recently reported for their unusual pigmentation properties. A possible role for the malonyl group (frequently encountered in the structure of naturally occurring anthocyanins) in plant colour expression is outlined for the first time.

Notes: The inhibition of δ-chymotrypsin with optically active, axially and equatorially substituted trans-3-(2,4-dini-trophenoxy)-2,4-dioxa-3λ5-phospbubicyclo[4.4.0]decan-3-ones ( = hexahydro-4H-1,3,2-benzodioxaphosphorin 3-oxides) was investigated. Their inhibitory power was determined by kinetic measurements, and the stereochemical course of the reaction of stoichiometric amounts of the enzyme and inhibitor was monitored with 31P-NMR spectroscopy at pH 7.8. The irreversible inhibitors show significant enantioselectivity (the (Sp)-enantiomer reacting faster) and yield diastereoisomeric, covalently phosphorylated derivatives of δ-chymotrypsin.31P-NMR Spectroscopic studies of the inhibition by the axially substituted inhibitor revealed for the racemic (±)-2a first a resonance at -4.4 ppm and later, while inhibition proceeded, a second one at -4.5 ppm. The reaction with optically active (+)-2a showed only one signal at -4.4 ppm and its enantiomer (-)-2a only one signal at -4.5 ppm. Using the equatorially substituted racemic epimer (±)-2b, we observed the main resonance at -5.3 ppm and two minor ones at -4.4 and -4.5 ppm. The optically active compound (+)-2b showed two peaks at -4.5 and -5.3 ppm, whereas its antipode (-)-2b revealed two signals at -4.4 and -5.3 ppm.Comparing the 31P chemical shifts of the corresponding covalent phosphoserine derivatives 4a (-5.7 ppm, axial) and 4b (-4.5 ppm, equatorial) shows the inhibition with the axial compounds 2a to proceed via neat inversion of the configuration at the P-atom, whereas the equatorial epimers 2b with a higher conformational flexibility seem to follow a different stereochemical pathway which results in both inversion and retention.

Notes: The synthesis of three novel pyrazole-containing complexing acids, N,N,N′,N′-{2, 6-bis[3-(aminomethyl)pyrazol-1-yl]-4-methoxypyridine}tetrakis(acetic acid)(1), N,N,N′,N′-{2, 6-bis[3-(aminomethyl)pyrazol-1-yl]pyrazine}-tetrakis(acetic acid) (2), and N,N,N′,N′-{6, 6′-bis[3-(aminomethyl)pyrazol-1-yl]-2, 2′-bipyridine}tetrakis(acetic acid) (3) is described. Ligands 1-3 formed stable complexes with EuIII, TbIII, SmIII, and DyIII in H2O whose relative luminescence yields, triplet-state energies, and emission decay lifetimes were measured. The number of H2O molecules in the first coordination sphere of the lanthanide ion were also determined. Comparison of data from the EuIII and TbIII complexes of 1-3 and those of the parent trisheterocycle N,N,N′,N′-{2, 6-bis[3-(aminomethyl)pyrazol-l-yl]pyridine}tetrakis(acetic acid) showed that the modification of the pyridine ring for pyrazine or 2, 2′-bipyridine strongly modify the luminescence properties of the complexes. MeO Substitution at C(4) of 1 maintain the excellent properties described for the parent compound and give an additional functional group that will serve for attaching the label to biomolecules in bioaffinity applications.

Notes: Simple recommendations for the configurational description of chiral fullerenes and fullerene derivatives with a chiral functionalization pattern are presented in detail and illustrated with examples for different types of compounds. The descriptor system is based on the fact that the numbering schemes proposed for fullerenes are chiral (helical) and, thus, constitute an ideal reference for differentiating between enantiomers of chiral carbon cages and of fullerene derivatives with a chiral functionalization pattern. A single descriptor is sufficient to specify the configuration of the chiral spheroids, regardless of their functionalization degree. According to the helicity of the numbering scheme to be used, the descriptors are fC (clockwise) or fA (anticlockwise). The proposed configurational description can also be extended to related classes of compounds such as chiral bowl-shaped condensed ring systems and their derivatives with a chiral functionalization pattern.

Notes: Three binuclear copper(II) complexes, [Cu2(μ-L)(μ-N3)](ClO4)2′ 1-5 EtOH (1), [Cu2(μ-L)(μ-MeO)(ClO4)]-ClO4 - EtOH (2) and [Cu2(μ-L)(μ-C3H3N2)](ClO4)2 · 2H2O, (3) where L is the pentadentale bridging ligand derived from 5-(tert-butyl)-2-hydroxybenzene-1, 3-dicarbaldehyde bis(benzoylhydrazone) (HL) were synthesized and characterized. The crystal-structure determination of complex 2 provided the following crystal data: monoclinic, space group P21}/a, a = 11.412(2), b = 24.509(4), c = 14.833(4) Å, β = 104.41(2)°, K = 4018(3) Å3, Z = 4. The structure shows that the CuII ions are bridged by the endogenous phenolato O-atom and by an exogenous bridge CH3O-. The analysis of variable-temperature magnetic susceptibility data (4-300 K.) indicates that there is an antiferromagnetic interaction between the CuII ions in these complexes with an exchange parameter (2J) of -119.1 cm-1 for complex 1 and -361.8 cm-1 for complex 3. The effect of some exogenous bridging ligands on magnetic coupling for this type of complex is suggested.

Notes: The syntheses of several N-aryl-3-amino-4-nitroisothiazol-5(2H)-imines 12 from 3, 3-diamino-2-nitro-thioacrylamides 11 are reported (Scheme 3). In polar solvents, a spontaneous isomerization of some of the prepared isothiazol-5(2H)-imines 12 yielded benzothiazoles 13 (Scheme 4). In the case of 2-alkyl-substituted derivatives of type 12, the isomerization occurred only at higher temperatures. Electronic influences of different substituents on the rate of the isomerization were studied, and a polar reaction mechanism is proposed in Scheme 6. The structures of 12e and 13e were established by X-ray crystallography. Conformational analyses of 3-(methylamino)-2-nitro-N-phenyl-3-(pyrrolidin-1-yl)thioacrylamide (111) by NMR and X-ray methods were performed with the aim of explaining the distinct behavior of this amide towards Br2 or diethyl azodicarboxylate.

Notes: The 7-deaza-2′-deoxy-7-methylguanosine (2b) [9], which is the glycosylic-bond-stable, noncharged analogue of 2′-deoxy-7-methylguanosine (1b), was incorporated in DNA by solid-phase synthesis. As building blocks, the protected phosphonatc 3a and the phosphoramidite 3b were prepared. The 7-methyl group of 2b stabilizes the B-DNA duplex compared to 7-deaza-2′-deoxyguanosine but does not induce a B-Z transition as it is known from compound 1b. The stabilization by the 7-deaza-7-methylguanine moiety is sequence-dependent, and the nearest-neighbor influence is different from that of 7-deazaguanine. Homooligonucleotides of 2b show sigmoidal melting indicating a highly ordered single-stranded structure. In general, Oligonucleotides containing 2b are very stable against hydrolysis with calf-spleen phosphodiesterase (CS-PDE, 5′ → 3′ exonuclease), while phosphodiester hydrolysis with snake-venom phosphodiesterase (SV-PDE, 3′ → 5′ exonuclease) is only slightly reduced.

Notes: The selective N-monoderivatization of propane-1,3-diamine (5) with carbonyl and sulfonyl chlorides via2-phenylhexahydropyrimidine (6) was compared with the direct statistic monoderivatization. It was found that, under optimized conditions, both methods are competitive to one another, depending, however, strongly on the reactivity of the eleclrophile used. The ‘hexahydropyrimidine method’ is more reliable with respect to yields, which are moderate but invariably between 54 and 69%, whereas the ‘statistic method’ leads in certain cases to exceptionally high yields (up to 96%), in others, however, almost none.

Notes: N, N-Dimethylformamide dimethyl acetal transforms an allylic OH group, which is part of a tetracyclic hydrocarbon in a unique elimination reaction into a [5.5.5.5]fenestradiene (2b → 4). In topologically selective reactions of this diene 4 with [Fe2(CO)9,], the [Fe(CO)4(η2-diene)] and the [Fe(CO)3(η4-diene)] complexes 8 and 9, respectively, are formed by complexation on one side of the diene moiety, whereas complexation on the other side leads to a [Fe(CO)2(Cp)] complex 10.

Notes: 1,3-Dipolar Cycloadditions of a Carhonyl-ylide with 1,3-Thiazole-5(4H)-thiones and ThioketonesInp-xylene at 150°, 3-phenyloxirane-2,2-dicarbonitrile (4b) and 2-phenyl-3-thia-1-azaspiro[4.4]non-1-ene-4-thione (1a) gave the three 1:1 adduets trans-3a, cis-3a, and 13ain 61, 21, and 3% yield, respectively (Scheme 3). The stereoisomers trans-3a and cis-3a are the products of a regioselective 1,3-dipolar cycloaddition of carbonylylide 2b, generated thermally by an electrocyclic ring opening of 4b (Scheme 6), and the C=S group of 1a. Surprisingly, 13a proved not to be a regioisomeric cycloadduct of 1a and 2b, but an isomer formed via cleavage of the O—C(3) bond of the oxirane 4b. A reaction mechanism rationalizing the formation of 13a is proposed in Scheme 6. Analogous results were obtained from the reaction of 4b and 4,4-dimethyl-2-phenyl-1,3-thiazole-5 (4H)-thione (1b, Scheme 3). The thermolysis of 4b in p-xylene at 130° in the presence of adamantine-thione (10) led to two isomeric 1:1 adducts 15 and 16 in a ratio of ca. 2:1, however, in low yield (Scheme 4). Most likely the products are again formed viathe two competing reaction mechanisms depicted in Scheme 6. The analogous reactions of 4b with 2,2,4,4-tetramethylcyclobutane-1,3-thione (11) and 9H-xanthene-9-thione (12) yielded a single 1:1 adduct in each case (Schemes). In the former case, spirocyclic 1,3-oxathiolane 17, the product of the 1,3-dipolar cycloaddition with 2a corresponding to 3a, was isolated in only 11 % yield. It is remarkable that no 2:1 adduct was formed even in the presence of an excess of 4b. In contrast, 4b and 12 reacted smoothly to give 18 in 81 % yield; no cycloadduct of the carbonylylide 2a could be detected. The structures of cis-3a, 13a, 15, and 18, as well as the structure of 14, which is a derivative of trans-3a, have been established by X-ray crystallography (Figs. 1-3, Table).

Notes: The complexing behaviour of 2,2′-bithiazole-containing calix[4]arenes towards Cu1 was investigated. The extinction of the intrinsic blue fluorescence of the free ligands upon addition of stoichiometric amounts of the metallic salt was used as complexation probe. This extinction was directly related to the chelation of the metal and allowed the controlled synthesis of new mono- and dimetalic complexes which were fully characterized.

Notes: The base-pairing properties of N7-(2-deoxy-β-D-erythro-pentofuranosyl)guanine (N7Gd; 1) are investigated. The nucleoside 1 was obtained by nucleobase-anion glycosylation. The glycosylation reaction of various 6-alkoxy-purin-2-amines 3a-i with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D-erythro-pentofuranosyl chloride (8) was studied. The N9/N7-glycosylation ratio was found to be 1:1 when 6-isopropoxypurin-2-amine (3d) was used, whereas 6-(2-methoxyethoxy)purin-2-arnine (3i) gave mainly the N9-nucleoside (2:1). Oligonucleotides containing compound 1 were prepared by solid-phase synthesis and hybridized with complementary strands having the four conventional nucleosides located opposite to N7Gd. According to Tm values and enthalpy data of duplex formation, a base pair between N7Gd and dG is suggested. From the possible N7Gd dG base pair motives, Hoogsteen pairing can be excluded as 7-deaza-2′-deoxyguanosine forms the same stable base pair with N7Gd as dG.

Notes: To improve cell permeability, monomeric 3′-deoxyadenosine (cordycepin) and antivirally active trimeric 3′-deoxyadenylyl-(2′-5′)-3′-deoxyadenylyl-(2′-5′)-3′-deoxyadenosine (2′-5′)d3 (A-A-A); (cordycepin-trimer core) were modified at the 2′-O- or 5′-O-position by myristic, cholic, and folic acid = tetradecanoic, 3α, 7α, 12α -trihy-droxy-5β-cholan-24-oic, and N-{4-{[(2-amino-3,4-dihydro-4-oxopteridin-6-yl)methyl]amino}benzoyl}-L-glutamic acid, resp., linked by a 6-aminohexamoyl spacer. Syntheses of the trimeric educts 21, 27, and 28 were performed by phosphoramidite chemistry, using β-eliminating 2-(4-nitrophenyl)ethyl (npe), 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) and (9H-fluoren-9-yl)methoxycarbonyl (fmoc) groups which allow a deprotection by DBU in an aprotic solvent without harming the ester-bounded conjugates, to give the products 24-26 and 31-33. The metabollically stable (2′-5′)A derivatives 26 and 33, covalently linked to folic acid either at the 2′-terminus or at the 5′-terminus of (2′-5′)d3′(A-A-A), respectively, are a new class of the anti-HIV-1 compounds. Inhibition of HIV-1 reverse transcriptase (RT) activity by 26 and 33 was 45 and 81%, respectively. Only 33 activated recombinant, human RNase L by 35%.

Notes: The [Rh2(OAc)4]-catalyzed decomposition of {[(4-nitrophenyl)sulfonyl]imino}phenyl-λ3-iodane (NsN=IPh) resulted in formal insertions into CH bonds, activated by phenyl or vinyl groups, or by O-substituents. Scope and limitations of the reaction were investigated. Yields of up to 84% were achieved in the most favorable cases. Yields were enhanced by electron-releasing substituents and decreased by steric hindrance. Aziridination competed with allylic insertion with olefinic substrates. The insertion reaction proceeded with retention of configuration. With chiral RhII catalysts, a modest asymmetric induction was observed. A mechanism involving direct insertion by a Rh-complexed nitrene into the CH bond is proposed.

Notes: The ease of thermal breaking of the C(sp3)—O bond of the 2-aryl-2-methyl-2H-1-benzopyrans 1-9 was evaluated by measuring the free energy (ΔGe≠) of the racemization reaction of optically active compounds. The variation of ΔGe≠ of the thermal ring opening in terms of structural modifications is discussed. The synthesis of the studied compounds, the preparative separation of enantiomers by liquid chromatography, the determination of enantiomeric purity, the circular dichroism of enriched enantiomers, and the measurement of rate constants of enantiomerization by monitoring the decrease of the polarimetric angle of rotation at suitable temperatures are described.

Notes: Bovine β-1,4-galactosyltransierase is an efficient catalyst for the regioselective transfer of galactose from UPD-galactose, generated in situ with the UDP-glucose/UDP-glucose-4-epimerase system, to the kaurane glycosides stevioside (1) and Steviolbioside (2), affording the corresponding galactosyl derivatives 3 and 4 in high yields. By a combination of 2D NMR techniques (COSY, TOCSY, ROESY, HMQC, and HMBC), the structure of the products is established as 13-[(β -D-galactopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 2)- β -D-glucopyranosyl)oxy]kaur-16-en-19-oic acid β -D-glucopyranosyl ester (3) and 13-[(β-D-galactopyranosyl-(1 → 4)- β-D-glu-copyranosyl-(1 → 2)- β-D-glucopyranosyl)oxy]kaur-16-en-19-oic acid (4).

Notes: The synthesis and structural characterization of the vitamin B12 derivatives 9 and 10 equipped with a peripheral EDTA (ethylenediaminetetraacetic acid) binding site is described. It is based on the condensation of an activated ester of cobester-c-acid with ethane-1,2-diamine or 2-aminoethanol followed by acylation of the resulting amines with the monoanhydride 8 of EDTA. The title compounds 9 and 10 can be used as modifiers for metal oxide semiconductor electrodes and are potential precursors for the synthesis of bimetallic, supramolecular catalysts.

Notes: The Fe+-mediated [4+2] cycloaddition of dienes with alkynes has been examined by four-sector ion-beam and ion cyclotron resonance mass spectrometry. Prospects and limitations of this reaction were evaluated by investigating several Me-substituted ligands. Me Substitution at C(2) and C(3) of the diene, i.e., 2-methylbuta-1,3-diene, 2,3-dimethylbuta-1,3-diene, hardly disturbs the cycloaddition. Similarly, variation of the alkyne by use of propyne and but-2-yne does not affect the [4+2] cycloaddition step, but allows for H/D exchange processes prior to cyclization. In contrast, Me substituents in the terminal positions of the diene moiety (e.g., penta-1,3-diene, liexa-2,4-diene) induce side reactions, namely double-bond migration followed by [3+2] and [5+2] cycloadditions, up to almost complete suppression of the [4+2] cycloaddition for 2,4-dimethylhexa-2,4-diene. Similarly, alkynes with larger alkyl substituents (pent-1-yne, 3,3-dimethylbut-1-yne) suppress the [4 + 2] cycloaddition route. Stereochemical effects have been observed for the (E)- and (Z)-penta-1,3-diene ligands as well as for (E,E)- and (E,Z)-hexa-2,4-diene. A mechanistic explanation for the different behavior of the stereoisomers in the cyclization reaction is developed. Further, the regiochemical aspects operative in the systems ethoxyacetylene/pentadiene/Fe+ and ethoxyacetylcne/isoprene/Fe+ indicate that substituents avoid proximity.

Notes: Absolute rate constants for the addition of the highly nucleophilic 2-hydroxy-2-propyl radical to eight fast-reacting 1- and 1,1-disubstituted alkenes in MeOH at room temperature have been determined by laser flash photolysis. Also the absorption spectra of the 2-hydroxy-2-propyl and the benzylic and alkyl-type adduct radicals are presented. The rate constants were obtained using various methods for the analysis of the kinetic traces and support earlier findings.

Notes: Chemistry of α-Aminonitriles. Regioselective Synthesis and Crystal Structure of Uroporphyrinogen (Type I) OctanitrileA regioselective synthesis of uroporphyrinogen-octanitrile (type I) based on the strategy of multiple use of (dimethylmethylidene)ammonium iodide for stepwise regioselective functionalization of the pyrrole nucleus is described. This uroporphyrinogen derivative is remarkably stable and beautifully crystallizes in space group P1 with one molecule per unit cell. The crystal structure of the compound shows interesting conformational characteristics which are interpreted to be caused by subtle stereoelectronic effects. The English Footnotes to Schemes 1-3 and Figs. 1-12 provide an extension of this summary.

Notes: The synthesis of glycopeptides carrying tumour-associated antigens is of interest for cancer diagnosis and treatment. Here, a very efficient route lo disaccharide threonine building block 8 is presented which allows the introduction of the sialyl-Tn antigen into a peptide. The syntheses of the undecapeptide and the sialyl-Tn-containing glycoundecapeptide, which are a part of the repeating unit of MUC1, were performed by solid-phase synthesis with an allylic anchor cleavable under neutral conditions. After detachment from the resin, the peptide and the glycopeptide arc completely deprotected giving the target compounds 13 and 15, respectively.

Notes: The heterospirocyclic N-methyl-N-phenyl-2H-azirin-3-amines (3-(N-methyl-N-phenylamino)-2H-azirines) 1a-d with a tetrahydro-2H-thiopyran, tetrahydro-2H-thiopyran, and a N-protected piperidine ring, respectively, were synthesized from the corresponding heterocyclic 4-carboxamides 2 by consecutive treatment with lithium diisopropylamide (LDA), diphenyl phosphorochloridate (DPPCI), and sodium azide (Scheme 4). The reaction of these aminoazirines with thiobenzoic acid in CH2Cl2 at room temperature gave the thiocarbamoyl-substituted benzamides 13a-d in high yield. The azirines 1a-d were used as synthons for heterocyclic α-amino acids in the preparation of tripeptides of the type Z-Aib-Xaa-Aib-N(Ph)Me (18) by following the protocol of the ‘azirine/oxazolone method’: treatment of Z-Aib with 1 to give the dipeptide amide 15, followed by selective hydrolysis to the corresponding acid 16 and coupling with the 2,2-dimethyl-2H-azirin-3-amine 17 gave 18, again in high yield (Scheme 5). With some selected examples of 18, the selective deprotection of the amino and the carboxy group, respectively, was demonstrated (Scheme 6). The solid-state conformations of the protected tripeptides 18a-d, as well as that of the corresponding carbocyclic analogue 18e, were determined by X-ray crystallography (Figs. 1-3 and Tables 1-3). All five tripeptides adopt a β-turn conformation of type III or III′. The solvent dependence of the chemical shifts of the NH resonances (Fig. 6) suggests that there is an intramolecular H-bond between H-N(4) and O(11) in all cases, which is an indication that a relatively rigid β-turn structure also persists in solution. Surprisingly, the tripeptide acid 20a shows no intramolecular H-bond in the crystalline state (Fig. 7); O(11) is involved in an intermolecular H-bond with the OH group of the carboxy function.