Showing papers in "Helvetica Chimica Acta in 1992"

On the Mechanisms of Enantioselective Reactions Using α,α,α′,α′ -Tetraaryl-1,3-dioxolane-4,5-dimethanol(TADDOL)-Derived Titanates: Differences between C2- and C1-symmetrical TADDOLs – facts, implications and generalizations†

Abstract: The titanates derived from α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs, prepared from tartrate) act as catalysts for enantioselective additions of dialkylzinc compounds to aldehydes. For the standard reaction chosen for this investigation of the mechanism, the addition of diethylzinc to benzaldehyde, there is very little change of selectivity with different aryl substituents on the TADDOLate ligands (Tables 2–4, examples). With 0.02 to 0.2 equiv. of the chiral titanates, selectivities above 90% are observed only in the presence of excess tetraisopropyl titanate! According to NMR measurements (Fig. 2), the chiral bicyclic titanate and the achiral titanate do not react to give new species under these conditions. From experiments with different stoichiometries of the components, and with different achiral or chiral OR groups on the Ti-atom of the seven-membered ring titanate, it is concluded (i) that a single chiral titanate is involved in the product-forming step, (ii) that the bulky TADDOLate ligand renders the Ti-center catalytically more active than that of (i-PrO)4Ti, due to fast dynamics of ligand exchange on the sterically hindered Ti-center (Table 5, Fig. 3), and (iii) that the role of excess (i-PrO)4Ti is to remove – by ligand exchange – the product alkoxides (R*O) from the catalytically active Ti-center (Scheme 4, Table 6). Three new crystal structures of TADDOL derivatives (two clathrates with secondary amines, and a dimethyl ether) have been determined by X-ray diffraction (Figs. 5–7), and are compared with those previously reported. The distances between the C(aryl)2O oxygen atoms in the C2- and C1-symmetrical structures vary from 2.58 to 2.94 A, depending upon the conformation of their dioxolane rings and the presence or absence of an intramolecular H-bond (Fig. 8). A single-crystal X-ray structure of a spiro-titanate, with two TADDOLate ligands on the Ti-atom, is described (Fig. 9); it contains six different seven-membered titanate-ring conformations in the asymmetric unit (Fig. 10), which suggests a highly flexible solution structure. The structures of Ti TADDOLate complexes are compared with those of C2-symmetrical Ru, Rh, and Pd disphosphine chelates (Table 7). A common topological model is presented for all nucleophilic additions to aldehydes involving Ti TADDOLates (Si attack with (R,R)-derivatives, relative topicity unlike; Fig. 11). Possible structures of complexes containing bidentate substrates for Ti TADDOLate-mediated ene reactions and cycloadditions are proposed (Fig. 12). A simple six-membered ring chair-type arrangement of the atoms involved can be used to describe the result of TADDOLate-mediated nucleophilic additions to aldehydes and ketones, with Ti, Zr, Mg, or Al bearing the chiral ligand (Scheme 6). A proposal is also made for the geometry of the intermediate responsible for enantioselective hydrogenation of N-(acetylamino)cinnamate catalyzed by Rh complexes containing C2-symmetrical diphosphines (Fig. 13).

Catalytic asymmetric synthesis of Secondary (E)-allyl alcohols from acetylenes and aldehydes via (1-alkenyl)zinc intermediates. Preliminary Communication

Abstract: Hydroboration of aliphatic 1-alkynes with freshly prepared dicyclohexylborane (1 mol-equiv., hexane), treatment of the resulting [(E)-1-alkenyl]boranes 5 with Et2Zn or Me2Zn (1.05 mol-equiv.) followed by addition of (−)-3-exo-(dimethylamino)isoborneol (DAIB, 8; 0.01 mol-equiv.), subsequent addition of a solution of an aromatic or aliphatic aldehyde (1 mol-equiv., hexane), and quenching with aq. NH4Cl provided (E)-allyl alcohols 6 usually in 70–95% yield with 79–98% enantiomeric excess (Scheme 3 and Table).

Warum Pentose‐ und nicht Hexose‐Nucleinsäuren?? Teil I. Einleitung und Problemstellung, Konformationsanalyse für Oligonucleotid‐Ketten aus 2′,3′‐Dideoxyglucopyranosyl‐Bausteinen (‘Homo‐DNS’) sowie Betrachtungen zur Konformation von A‐ und B‐DNS

Abstract: Why Pentose and Not Hexose Nucleic Acids? Part I. Introduction to the Problem, Conformational Analysis of Oligonucleotide Single Strands Containing 2′,3′-Dideoxyglucopyranosyl Building Blocks (‘Homo-DNA’), and Reflections on the Conformation of A- and B-DNA Summary in collaboration with Prof. Dr. C.E. Wintner, Haverford College, Haverford, PA 19041-1392; academic guest, ETH, March and June/July, 1991. Chemical rationalization of the structure of a biomolecule can be sought through consideration of two criteria: first, the relationship between the structure and its biological function; and second, the structure's potential for constitutional self assembly. The latter criterion convers the judgment, by chemical reasoning, of the chance of its preformation, that is, a synthetic event which must have been undergone by any molecular structure in order to have been selected (or to have selected itself) to become a biomolecule. One way to further the task of rationalizing a biomolecule's structure by experimental means is the design, synthesis, and study of structural alternatives which might have become biomolecules on the basis of either criterion, but which do not, in fact, appear in Nature today. In the formation of sugar phosphates from glycolaldehyde phosphate under basic conditions, straightforward and selective formation of rac-hexose 2,4,6-triphosphates is observed in the absence of formaldehyde, while rac-pentose 2,4-diphosphates are dominant, when (0.5 equiv.) formaldehyde is present [1]. This and other observations indicate that hexose sugars should be regarded to have had a chance of preformation comparable with that of pentose sugars. Why, then, did Nature choose pentoses and not hexoses as the sugar building blocks of nucleic acids? The reason must be functional; it must be the case that pentose nucleic acids are biologically superior to potential hexose alternatives. To the extent that biological function is a consequence of molecular structure and reactivity, the origin of this superiority should be decipherable through chemical experiment, that is, through synthesis of hexose nucleic acids, systematic study of their chemical properties, and comparison of these properties with those of their natural counterparts. This has been the object of the present investigation, initiated in 1986. The paper introduces a series of papers which will describe the results of a model study, namely, the synthesis, pairing properties and structure of homo-DNA oligonucleotides.

Synthesis, Isolation, and NMR‐Spectroscopic Characterization of Fourteen (Z)‐Isomers of Lycopene and of Some Acetylenic Didehydro‐ and Tetradehydrolycopenes

Abstract: Eight (Z)-isomers of lycopene were prepared by stereocontrolled syntheses and fully characterized by 1H-NMR, 13C-NMR, mass, and UV/VIS spectroscopy: (5Z)-, (7Z)-, (15Z)-, (5Z,5′Z)-, (7Z,7′Z)-, (7Z,9Z)-, (9Z,9′Z)-, and (7Z,9Z,7′Z,9′Z)-lycopene. Six additional (Z)-isomers, namely (9Z)-, (13Z)-, (5Z,9′Z)-, (9Z,13′Z)-, (5Z,9Z,5′Z)-, and (5Z,13Z,5′Z)-lycopene, were isolated in small quantities from isomer mixtures by semiprep. HPLC and were identified by 1H-NMR spectroscopy.

New 2,2'-bipyridine derivatives and their luminescence properties with europium(III) and terbium(III) ions

Abstract: Twenty differently substituted 2,2′,2″,2‴ -[(2,2′-bipyridine-6,6′-diyl)bis(methylenenitrilo)]tetrakis(acetc acids) 75–94 were synthesized with the purpose of developing new markers to be used in bioaffinity assays based on the unique luminescence properties of EuIII and TbIII ions. The relative luminescence yields, excitation maxima, and emission decay constants were determined for the corresponding EuIII and TbIII chelates. The substituents at the bipyridine moiety had a significant effect on the luminescence properties: the best relative luminescence yields R were obtained for ligands with electron-donating substituents (e.g. Me, Ph), electron-withdrawing substituents (e.g. NO2, COOH) had a reverse effect. However, no clear correlation between the relative luminescence yields and the substituent parameters was found.

New Heteroaromatic Complexing Agents and Luminescence of Their Europium(III) and Terbium(III) Chelates

Abstract: Twelve heteroaromatic complexing agents 9a–I were synthesized with the purpose to develop suitable labels for time-resolved luminescence-based bioaffinity assays. The relative luminescence yields, excitation maxima, and emission decay constants of their europium(III) and terbium(III) chelates were determined. According to these results, 2,2′,2″,2‴-[(2,2′-bipyridine-6,6′-diyl)bis(methylenenitrilo)]tetrakis (acetic acid) (9e) and 2,2′,2″,2‴-[(2,2′:6′,2″-terpyridine-6,6″-diyl)bis(methylenenitrilo)] tetrakis(acetic acid) (91) are the most promising agents.

Warum Pentose- und nicht Hexose-Nucleinsäuren??. Teil II. Oligonucleotide aus 2′,3′-Dideoxy-β-D-glucopyranosyl-Bausteinen (‘Homo-DNS’): Herstellung.†

Abstract: Why Pentose and Not Hexose Nucleic Acids? Part II. Preparation of Oligonucleotides Containing 2′,3′-Dideoxy-β-D-glucopyranosyl Building Blocks(7) This paper describes the preparation of the 2′,3′-dideoxy-β-D-glucopyranosyl-( = 2′,3′-dideoxy-β-D-erythro-hexopyranosyl)-derived nucleosides of the five bases adenine, cytosine, guanine, thymine, and uracil ( = ‘homo-de-oxyribonucleosides’) as well as the synthesis of oligonucleotides derived from them. The methods used for both nucleoside and oligonucleotide synthesis closely follow the known methods of synthesis in the corresponding series of natural 2′-deoxyribonucleosides and oligonucleotides. The efficient methods of automated DNA synthesis proved to be fully applicable to the synthesis of homo-DNA oligonucleotides, the only change necessary for achieving satisfactory coupling yields being a slight lengthening of the coupling time. Homo-DNA oligonucleotides with chain lengths of up to twelve nucleoside units were assembled on solid support either manually or on a commercial DNA synthesizer in scales of 0.4 μmol to as much as 200 μmol and were purified by either reversed-phase or ion-exchange HPLC to single-peak purity according to both chromatographic systems (estimated purity > 95%). The choice of the specific base sequences to be synthesized was determined primarily by the constitutional problems of base pairing that emerged from experimental observations made in the course of systematic studies of the pairing properties of homo-DNA oligonucleotides. About 100 homo-DNA sequences were prepared for this purpose. Their pairing properties will be described in Part III of this series; the present paper is restricted to the characterization of the purity and constitutional integrity of a few selected (single-stranded) oligonucleotides by 1H-, 31P-, and 13C-NMR spectroscopy as well as by FAB and time-of-flight mass spectroscopy. The English Footnotes to Schemes 1–9, Fig. 1–12, and Table 1 provide an extension of this summary.

Structure and Reactivity of Five- and Six-Ring N, N-, N, O-, and O, O-acetals: A lesson in allylic 1, 3-strain (A1, 3 strain)

Abstract: The X‐ray structures of fifteen 1, 3‐imidazolidine, 1, 3‐oxazolidine, 1, 3‐dioxan‐4‐one, and hydropyrimidine‐4(1H)‐one derivatives are described (Table 2) and compared with known structures of similar compounds (Figs. 1–20). The differences between structures containing exocyclic N‐acyl groups and those lacking this structural element arise from the A1,3 effect of the amide moieties. Even t‐Bu groups are forced into axial positions of six‐ring half‐chair or into flag‐pole positions of six‐ring twist‐boat conformers by this effect (Figs. 16–20). In the N‐acylated five‐membered heterocycles, a combination of ring strain and A1, 3 strain leads to strong pyramidalizations of the amide N‐atoms (Table 1) such that the acyl groups wind up on one side and the other substituents on the opposite side of the rings (Figs. 4–9 and Scheme 3). Thus, the acyl (protecting!) groups strongly contribute to the steric bias between the two faces of the rings. Observed, at first glance surprizing stereoselectivities of reactions of these heterocycles (Schemes 1 and 2) are interpreted (Scheme 3) as an indirect consequence of the amide A1, 3 strain effect. The conclusions drawn are considered relvant for a better understanding of the ever increasing role which amide groups play in stereoselective syntheses. Copyright © 1992 Verlag GmbH & Co. KGaA, Weinheim

Metal-ion-coordinating properties of various phosphonate derivatives, including 9-[2-(phosphonylmethoxy(ethyl]adenine (PMEA)- an adenosine monophosphate (AMP) analogue) with antiviral properties

Abstract: The stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, (in part) Zn2+, or Cd2+ and (phosphonylmethoxy)ethane (PME2−) or 9−[2−(phosphonylmethoxy)ethyl]adenine (PMEA2−) were determined by potentiometric pH titration in aqueous solution (I = 0.1M, NaNO3; 25°). The experimental conditions were carefully selected such that self-association of the adenine derivative PMEA and of its complexes was negligibly small; i.e., it was made certain that the properties of the monomeric [M(PMEA)] complexes were studied. Recent measurements with simple phosphate monoesters, R–MP2– (where R is a non-coordinating residue; S. S. Massoud, H. Sigel, Inorg. Chem.1988, 27, 1447), were used to show that analogously simple phosphonates (RPO) – we studied now the complexes of methyl phosphonate and ethyl phosphonate – fit on the same log K/logKvs. pK/ pK straight-line plots. With these reference lines, it could be demonstrated that for all the [M(PME)] complexes with the mentioned metal ions an increased complex stability is measured; i.e., a stability higher than that expected for a sole phosphonate coordination of the metal ion. This increased stability is attributed to the formation of five-membered chelates involving the ether oxygen present in the OCH2PO residue of PME2− (and PMEA2−); the formation degree of the five-membered [M(PME)] chelates varies between ca. 15 and 40% for the alkaline earth ions and ca. 35 to 65% for 3d ions and Zn2+ or Cd2+. Interestingly, for the [M(PMEA)] complexes within the error limits exactly the same observations are made indicating that the same five-membered chelates are formed, and that the adenine residue has no influence on the stability of these complexes, with the exception of those with Ni2+ and Cu2+. For these two metal ions, an additional stability increase is observed which has to be attributed to a metal ion-adenine interaction giving thus rise to equilibria between three different [M(PMEA)] isomers. These equilibria are analyzed, and for [Cu(PMEA)] it is calculated that 17(±3)% exist as an isomer with a sole Cu2+-phosphonate coordination, 34(±10)% form the mentioned five-membered chelate involving the ether oxygen, and the remaining 49(±10)% are due to an isomer containing also a Cu2+-adenine interaction. Based on various arguments, it is suggested that this latter isomer contains two chelate rings which result from a metal-ion coordination to the phosphonate group, the ether oxygen, and to N(3) of the adenine residue. For [Ni(PMEA)], the isomer with a Ni2+-adenine interaction is formed to only 22(±13)%; for [Cd(PMEA)] and the other [M(PMEA)] complexes if at all, only traces of such an isomer are occurring. In addition, the [M(PMEA)] complexes may be protonated leading to [M(H·PMEA)]+ species in which the proton is mainly at the phosphonate group, while the metal ion is bound in an adenosine-type fashion to the nucleic base residue. Finally, the properties of [M(PMEA)] and [M(AMP)] complexes are compared, and in this connection it should be emphasized that the ether oxygen which influences so much the stability and structure of the [M(PMEA)] complexes in solution is also crucial for the antiviral properties of PMEA.

Structural and photophysical properties of lanthanide nitrate 1:1 complexes with planar tridentate nitrogen ligands analogous to 2,2':6',2''-terpyridine

Abstract: The ligand 2,6-bis(1-methylbenzimidazol-2-yl)pyridine (mbzimpy, 1) reacts with EuIII to give [Eu(mbzimpy)(NO3)3(CH3OH)] [4] whose crystal structure (EuC22H21N8O10, a = 7.658(3) A, b = 19.136(2) A, c = 8.882 A, β = 104.07(1)°, monoclinic, P21, Z = 2) shows a mononuclear structure where EuIII is ten-coordinate by a meridional tridentate mbzimpy ligand, three bidentate nitrates, and one CH3OH molecule, leading to a low-symmetry coordination sphere around the metalion. Essentially the same coordination is found in the crystal structure of [Eu(obzimpy)(NO3)3] (8) (EuC35H45N8O9, a = 9.095(2) A, b = 16.624(2) A, c = 26.198(6) A, β = 95.85(1)°, monoclinic, P21/c, Z = 4) obtained by reaction of 2,6-bis(1-octylbenzimidazol-2-yl)pyridine (obzimpy, 2) with EuIII. Detailed photophysical studies of crystalline [Ln(mbzimpy)(NO3)3(CH3OH)] and [Ln(obzimpy)(NO3)3] complexes (Ln = Eu, Gd, Tb, Lu) show that 1 and 2 display 1ππ* and 3ππ* excited states very similar to those observed in 2,2′:6′,2″-terpyridine, leading to efficient ligand to LnIII intramolecular energy transfer. Spectroscopic results show that an extremely efficient mbzimpy-to-EuIII transfer occurs in [Ln(mbzimpy)(NO3)3(CH3OH)] and in the case of TbIII, a TbIII-to-mbzimpy back transfer is also implied in the deactivation process. The origin of these peculiar effects and the influence of ligand design by going from mbzimpy to obzimpy are discussed. 1H-NMR and luminescence data indicate that the structure found in the crystal is essentially maintained in solution.

Isolation of Toxic and Potentially Toxic Sesqui‐ and Monoterpenes from the Tropical Green Seaweed Caulerpa taxifolia Which Has Invaded the Region of Cap Martin and Monaco

Abstract: The green seaweed Caulerpa taxifolia (VAHL) C. AGARDH (Caulerpales), which, after its recent accidental introduction, is growing in the region of Cap Martin much more vigorously than in the tropics, is shown to contain the known sesquiterpenic toxins caulerpenyne (1) – in larger amounts than in tropical Caulerpales – and oxytoxin 1 (2). Novel, potentially toxic products isolated in small amounts from this seaweed include the sesquiterpenes taxifolial A ( = (5E)-6,10-dimethyl-2-[(E)2-oxoethylidene]undeca-5,9-dien-7- yne-1,3-diyl diacetate; 3), taxifolial B (= (1E,6E,10E)-3-[(Z)-acetoxymethylidene]-7, 11-dimethyl-12-oxododeca-1,6,10-trien-8-yne-1,4-diyl diacetate; 4), 10,11-epoxycaulerpenyne ( = (1E,6E)-3-[(Z)-acetoxymethylidene]-10,11-epoxy-7, 11-dimethyldodeca-1,6-dien-8-yne-1,4-diyl diacetate; 1:1 diastereoisomer mixture; 5), and taxifolial C ( = (2Z,6E)-3-formyl-7,11-dimethyldodeca-2,6,10-trien-8-yne-1,1, 4-triyl triacetate; 6), besides, as the first example of a monoterpene from the Caulerpales, taxifolial D ( = (2Z)-3,7-dimethylocta-2, 6-dien-4-ynal; 7).

Asymmetric Synthesis of α‐Amino Acids and α‐N‐Hydroxyamino Acids from N‐Acylbornane‐10,2‐sultams: 1‐chloro‐1‐nitrosocyclohexane as a practical [NH] equivalent

Abstract: Successive treatment of N-acylsultams 3 with sodium hexamethyldisilazide, 1-chloro-1-nitrosocyclohexane (1), and aq. HCl gave diastereoisomerically pure, crystalline N-hydroxyamino-acid derivatives 5. These were converted into various amino acids 7, N-hydroxyamino acids 8, and an N-Boc-amino acid 9. (S, S)-Isoleucine (17) and (S, S)-2-acetamido-3-phenylbutyric acid (23) were obtained from N-crotonoylsultam 15via 1,4-addition of an organomagnesium or organocopper reagent followed by enolate ‘amination’ with 1.

A New General Approach to Enantiomerically Pure Cyclic and Open-Chain (R)- and (S)-α,α-Disubstituted α-Amino Acids

Abstract: A wide range of cyclic and open-chain alpa,alpha-disubstituted alpha-amino acids 1a-p were prepared. The racemic N-acylated alpha,alpha-disubstituted amino acids were resolved by coupling to chiral amines 15-18 derived from (S)- phenylalanine to form diastereoisomers 19/20 or 21/22 that could be separated by crystallization and/or flash chromatography on silica gel (Scheme 3). Selective cleavage via the 1,3-oxazol-5(4H)-ones 10a-p gave the corresponding optically pure alpha,alpha-disubstituted amino-acid derivatives 11 or 12 in high yield (Scheme 3). The absolute configurations of the alpha,alpha-disubstituted amino acids were determined from X-ray structures of the diastereoisomers 20, 21g', 22d.

A complex pyrrolo-oxazinone and its iodo derivative isolated from a tunicate

Abstract: Two cytotoxic triphenylpyrrolo-oxazinones were isolated from a tunicate and their structures elucidated by spectral methods. Lukianol A ( = 3,7,8-tris(4-hydroxyphenyl)pyrrolo[2,1-c][1,4]oxazin-1 (1H)-one; 1) had MIC of 1 μg/ml in KB cytotoxicity tests; MIC value for 2 was 100 μg/ml.

Endohedral fullerene-noble gas clusters formed with high-energy bimolecular reactions of Cxn+ (x=60, 70; n=1,2,3)

Abstract: Results are reported for high-energy beam experiments which establish the formation of endohedral carbon cluster-noble gas compounds by bimolecular reactions of C (x = 60, 70; n = 1, 2, 3) with He and C with Ne. The ions were accelerated up to 8 ke V in a four-sector mass spectrometer and allowed to collide with the noble gas in a collision chamber at room temperatur. Product ions were monitored with a B/E = constant linked scan. Within the sensivity of the experiments, no carbon cluster-gas compounds were observed in the reactions of C with H2, D2, O2, Ar, and SF6, or of C with O2. The observed fall in the cross-section for carbon cluster-noble gas compounds with increasing size of the noble gas, the observation of unimolecular loss of C2 from mass-selected CxHe+ ions, and the elimination of carbon fragments instead of He observed in the formation of the collision-induced CxHen+ product ions are taken as evidence for endohedral compound formation. Results of ab initio molecular-orbital calculations for the perpendicular penetration of the plane of ionized benzene with He, Ne, and Ar indicate that sufficient kinetic energy should be available in the collisions with C to penetrate the C cage at the collision energies of the experiments.

Benzene Oxidation by ‘Bare’ FeO+ in the Gas Phase

Abstract: Bare FeO+ reacts in the gas phase with benzene at collision rate (k = 1.3 × 10−9 cm3 molecule−1 s−1), giving rise to the formation of Fe(C6H4)+/H2O(5%), Fe(C5H6)+/CO(37%), Fe(C5H5)+/CO/H. (2%), and Fe+/C6H5OH (56%). Neither the reaction rate nor the product distribution are subject to a significant kinetic isotope effect, thus, ruling out several mechanistic variants described in the literature to the operative for ‘analogous’ arene oxidation processes in solution. A mechanism is suggested which is in keeping with the experimental findings, and which also accounts for some remarkable results obtained, when two [Fe, C6,H6H6O]+ isomers are generated and subjected to a neutralization-re-ionization experiment in the gas phase.

Channel‐Type Molecular Structures. Part 2. Synthesis of Bouquet‐Shaped Molecules Based on a β‐Cyclodextrin Core

Abstract: A new series of channel-type molecules presenting the features of potential transmembrane structures is described They result from the grafting of amphiphilic side chains on a β-cyclodextrin derivative 3 that constitutes the organizing core They belong to the ‘bouquet’ family (B) Compounds bearing poly(oxyethylene) side chains, B16 and 17, and their polymethylene analogues B18 and 19, were synthesized The properties investigated emphasize the suitability of such molecules to be incorporated into lipid bilayer membranes

Cyclization of Hydroxyenol Ethers into Spiroacetals. Evidence for the position of the transition state and its implication on the stereoelectronic effects in acetal formation

Abstract: Acid-catalyzed cyclizations under thermodynamically and kinetically controlled conditions of the hydroxyenol ethers 18–21 are reported. Thermodynamically controlled cyclizations of 18, 19 and 21 produced only the more stable corresponding spiroacetals 22 and 27. Thermodynamically controlled cyclization of compound 20 produced a 1:1 mixture of non-epimerisable spiroacetals 24 and 26. On the other hand, kinetically controlled cyclizations of the same four hydroxyenol ethers produced, along with the more stable spiroacetals mentioned above, the less stable spiroacetals 23, 25, and 28. These results show that the kinetically controlled cyclization takes place via an early transition state which produces a mixture of the less stable and the more stable isomers. These results are explained by an early transition state taking into account the principle of stereoelectronic control while following the antiperiplanar lone-pair hypothesis (Burgi-Dunitz angle of attack of a nucleophile on a π system).

Synthesis and Properties of Macrobicyclic Cryptates Incorporating Five‐ and Six‐Membered Biheteroaryl Units

Abstract: The socium cryptates of the macrobicyclic ligands 1–6 have been synthesized by direct macrobicyclisation or by stepwise procedures. They incorporate 2,2′-bithiazole, 2,2′-biimidazole, 2.2′-bipyrimidine as well as 2,2′-bipyridine units. Treatment of the sodium complexes with europium(III) chloride gave the corresponding EuIII cryptates. The structural and spectral properties of these compounds are described. The EuIII complexes present characteristic 1H-NMR chemical-shift features. Their luminescence properties are described.

Glycosylidene Carbenes. Part 9. Regioselective glycosidation of diols and triols: Intra‐ and intermolecular hydrogen bonds

Abstract: Glycosidation of the myo-inositol derivatives 2 and 3 by the diazirine 1 yields 90% of a diastereoisomer pair of β-D-glycosides in a 1:1 ratio, i.e.5/6 and 7/8, respectively (Scheme 1). The crystal structure of 3 shows a strong intramolecular H-bond, which persists in solution, as indicated by FT-IR and 1H-NMR spectra. Yields and diastereoselectivity are lower for the glycosidation of 24 by 1 (Scheme 3). The resulting 1,2- and 1,4-linked disaccharides 25–28 were isolated as their acetates 29–32. The previously determined crystal structure of 24 shows no intramolecular H-bonds. The yield of the glycosidation of 24, but not of 3, depends upon the concentration, indicating that activation of 24 by intermolecular H-bonds is required. Glycosidation of 2 and 3 with the trichloroacetimidate 14 gave mixtures of four (5,6,15, and 16), and six (7,8, and 17–20) disaccharides, respectively (Scheme 2).

High-yield formation of arbutin from hydroquinone by cell-suspension cultures of Rauwolfia serpentina

Abstract: High-density cell-suspension cultures of Rauwolfia serpentina cultivated in a nutrition medium optimized for the production of the glucoalkaloid raucaffricine synthesize hydroquinone glycosides from continuously added hydroquinone with a total yield of 23.87 g/1 (18 g/1 of arbutin and 5.87 g/1 of a hydroquinone diglycoside) in 7 days. This arbutin production is by far the highest formation of a natural product by plant-cell-culture systems reported to date.

Carbocyclic analogs of nucleosides. Part 2.. Synthesis of 2′,3′‐dideoxy‐5′‐homonucleoside analogs

Abstract: A set of derivatives of cyclopentaneacetic acid cis-substituted at position 3 by nucleoside bases (both purines and pyrimidines) were prepared and characterized (see 11, 14, and 23a, b;Schemes 2–4). These molecules are carbocyclic analogs of 2′,3′-dideoxy-5′-homonucleosides. In this synthesis, the skeleton was constructed from norbornanone and a novel method based on Mitsunobu chemistry used for the introduction of nucleoside-base substituents. The scope of this method was further explored via the preparation of a cyclobutyl analog of dideoxyguanosine (see 17, Scheme 3).

Stereoselektive Synthese von (2S,6S)-2,6-Diaminoheptandisäure und von unsymmetrischen Derivaten der meso-2,6-Diaminoheptandisäure

Abstract: Stereoselective Synthesis of (2S,6S)-2,6-Diaminoheptanedioic Acid and of Unsymmetrical Derivatives of meso-2,6-Diaminoheptanedioic Acid Specific inhibition of enzymes of the diaminopimelate pathway (L-lysine biosynthesis) should, in principle, lead to selective antibacterial agents or herbicides. For this purpose, enantioselective syntheses were devised for (2S, 6S)-2, 6-diaminoheptanedioic acid (L, L-diaminopimelate, 1), (2R,6S)-2,6-diamino-2-methylhept-3-enedioic acid (10), (2R, 6S)-2, 6-diaminohept-3-enedioic acid (9), (2R, 6S)-2, 6-diamino-4-fluorohept-3-enedioic acid (42), and (2S, 6S)-2, 6-diamino-3-chloroheptanedioic acid (5). The Schollkopf bislactim-ether methodology was applied to control the configuration of C(2) and C(6) of 1, C(2) of 10, as well as C(6) of 9 and 42. Semialdehyde derivatives of L-glutamate afforded C(6) of 10 and 5, while the (R)-configurated C(2) of 9 and 42 were derived from L-serine. For this purpose, the synthesis of the Garner aldehyde 32 has been improved. As chromatographic purifications and the low temperatures for the reduction of the carboxylic acid are eliminated, this valuable intermediate can now be prepared in bulk quantities. An enantio- and diastereoselective aldol addition of a glycine titanium-enolate was applied for the construction of 5 (C(2) and C(3)). As all chiral building blocks and reagents used are available in both enantiomeric forms, these routes should also be suitable for the selective synthesis of the other stereoisomers of these bis(α-amino acids).

Preparation of Campholenal Analogues: Chirons for the lipophilic moiety of sandalwood-like odorant alcohols†

Abstract: In connection with structure-activity relationship studies, analogues of campholenal ((+)-4b), an important building block for sandalwood-like odorants, were prepared. The five-membered-ring analogues 4 were obtained by epoxidation of the corresponding α-pinene derivatives 2, followed by catalytic ZnBr2 isomerisation (Scheme 2). The six-membered-ring skeleton was obtained by ozonolysis of α-campholenyl acetate ((−)-14b), followed by intramolecular aldol condensation (Scheme 5). 13C-NMR assignments are given.

1,2‐Stereoinduction in Radicals and Anions: A comparison between hydrogen abstraction and protonation

Abstract: Chiral enolates 5 and 10, generated by radical addition and subsequent reduction, show diastereofacial selectivity during protonation. In the presence of substituted amines, diastereoselectivity is enhanced and becomes comparable to radical stereoselection. Diastereoselectivities up to 99:1 and yields up to 90% are reached.

Efficient Synthesis of Enantiomerically Pure α‐Ionone from (R)‐ and (S)‐α‐Damascone

Abstract: (R)- and (S)-α-ionone ((R)- and (S)-1, resp.) were prepared from (R)- and (S)-α-damascone ((R)- and (S)-3, resp.) without racemization in 48% yield employing a new enone transposition. The described transposition is complementary to existing methods whose application is often prohibited by the structural requirements of the substrate. The now easily accessible α-ionones of desired absolute configuration are useful as chiral building blocks for terpenoid synthesis.

α,α,α′,α′‐Tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols (TADDOLs) for Resolutions of Alcohols and as Chiral Solvating Agents in NMR Spectroscopy

Abstract: The use of α,α,α′,α′ -tetraaryl-1,3-dioxolane-4,5-dimethanols ( = TADDOLs;1) as chiral NMR shift reagents (1H, 13C, 19F) is described. In many cases, the ratio of enantiomeric alcohols and amines can be determined under standard conditions of measurement (CDCl3 as solvent, room temperature). The preparation and use of a new type of TADDOL, the tetrakis(dimethylamino) derivative 1d, is described. Menthol, octan-2-ol, and oct-1-yn-3-ol are partially resolved by crystallization of clathrates with 1c and 1d.

Non‐destructive Cleavage of N‐Acylsultams Under Neutral Conditions: Preparation of Enantiomerically, Pure Fmoc‐Protected α‐Amino Acids

Abstract: Heating diastereoisomerically pure N-acylsultams 3 or 4 with allyl alcohol/Ti(OR)4 efficiently yields sultams 1 or 2 and allyl esters 5. Esters 5 are hydrolyzed under nonbasic conditions in the presence of Wilkinson's catalyst to give enantiomerically and diastereoisomerically pure carboxylic acids 7. A series of [(fluoren-9-yl)methoxy]-carbonyl-(Fmoc)-protected amino acids 14 were thus prepared from N-[N'-(Fmoc)amino]acylsultams 12.

1,3,5‐Triamino‐1,3,5‐trideoxy‐cis‐inositol, a New Ligand with a Remarkable Versatility for Metal Ions. Part 2. Safe and efficient ligand preparation and structure of the free ligand and the CoIII complex

Abstract: A new, convenient, and safe route to 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (taci) was investigated by hydrogenation of azo-coupled derivatives of phloroglucinol. In the presence of acetic anhydride, the reduction of trisphenylazophloroglucinol (H2/Pd(5%) on C) resulted in the formation of tri-, hexa-, and nona-acetylated derivatives of triaminophloroglucinol. All three compounds are air-stable, colorless solids. However, the succeeding hydrogenation to the cyclohexane derivative failed. Trisodiumtris(p-sulfonatophenylazo)phloroglucinol could be hydrogenated in a one-pot reaction to the desired taci· 1.5H2SO4 using a Pt/Rh oxide as catalyst. taci provides two distinct chair conformations with either three amino or three hydroxy groups for metal binding. The unique metal-binding properties are discussed in terms of minimal conformational changes required for coordination. Conformational analysis, based on X-ray structural data of [BiCl6][H3(taci)] ·2 H2O (Pnma, a = 24.314 (5) A, b = 10.215 (2) A, c = 7.422 (8) A, R = 5.8%) and [Co(taci)2(NO3)3]·2H2O (C2/c, a = 22.912 (8) A, b = 8.942 (2) A, c = 14.731 (3) A, β = 128.66 (2)°, R = 4.9%) and the previously investigated [Cr(taci)2]3+ revealed an almost ideal chair conformation in all three molecules.

Homolytic Substitution Reaction at a Silicon Atom

Abstract: Tris(trimethylsilyl)silane (2) is an efficient hydrosilylating agent of 1,6-dienes 1 operating via a free-radical chain mechanism. The intermediate alkyl radical 3 attacks the second olefinic bond of the diene 1 and forms cyclopentylalkyl radical 4. Using a low concentration of the hydrogen donor 2, a radical substitution reaction at the Si-center of cis-4 occurs and yields the bicyclic silane 6. The rate of this homolytic substitution at the Si-atom is 2.4 · 105 s-1 (80°).