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A vinylsilane-ketiminium ion cyclization involving iminium species derived from amines 6 and 7 was investigated experimentally as a possible approach to some biologically interesting 1-azaspirocycles. However, even under conditions of microwave irradiation at high temperatures no such cyclization was observed whereas (in line with previous results) the corresponding vinylsilane-aldiminium ion cyclizations were more successful. Aldiminium species substituted alpha to nitrogen displayed no diastereoselectivity in the cyclization of precursors derived from 6 while high trans diastereoselectivity could be obtained for iminium species derived from 7. Quantum-mechanical investigations of the general reaction mechanism underlined the lack of reactivity of ketiminium species and also convincingly explained the observed diastereoselectivities of aldiminium species. The calculations further revealed that (Z)-vinylsilanes cyclize via a silicon-stabilized beta-carbocation, and that any formal aza-Cope rearrangement of the starting material to an allylsilane-iminium species does not take place in a concerted fashion. However, the calculations show that the aza-Cope rearrangement precedes cyclization for the corresponding (E)-vinylsilanes, the overall reaction being energetically slightly less favoured than cyclization of the (Z)-isomers.

International audience; We present a method for measuring absorption at the 1x10^(-5) cm^(-1) level in high-quality opticalmaterials. Using a Shack–Hartmann wave-front detector, thermal lensing in these materials may bemeasured. Then, the absorption coefficient may be estimated by fitting the observed deformation to athermal lensing model based on the temperature dependences of the refractive index and the thermalexpansion coefficient. For a particular sample of fused silica, the absorption coefficient was determinedto be 1.8±0.4x10^(-5) cm^(-1). Obtaining this result requires a resolution in the optical path length betterthan ±0.1 nm.

(E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the synthesis of enantiomerically pure enone 12 which is a key intermediate for the total synthesis of zoanthamine, a structurally complex marine natural product.

The selectivity-determining step in enantioselective copper-catalyzed cyclopropanation with diazo compounds has been studied by experimental and computational methods. The addition of the very reactive metallacarbene intermediate in an early transition state to the substrate alkene is concerted but strongly asynchronous, with substantial cationic character on one alkene carbon in the neighborhood of the transition state. Evidence from isotope effects and Hammett studies supports the nature of the transition state. Formation of a metallacyclobutane intermediate by a [2+2] addition is kinetically disfavored. Ligand-substrate interactions influencing the enantio- and diastereoselectivity have been identified, and the preferred orientation of the alkene substrate during the addition is suggested.

A new method for enantioconvergent synthesis has been developed. The strategy relies on the combination of an asymmetric Horner-Wadsworth-Emmons (HWE) reaction and a palladium-catalyzed allylic substitution. Different alpha-oxygen-substituted, racemic aldehydes were initially transformed by asymmetric HWE reactions into mixtures of two major alpha,beta-unsaturated esters, possessing opposite configurations at their allylic stereocenters as well as opposite alkene geometry. Subsequently, these isomeric mixtures of alkenes could be subjected to palladium-catalyzed allylic substitution reactions with carbon, nitrogen, and oxygen nucleophiles. In this latter step, the respective (E) and (Z) alkene substrate isomers were observed to react with opposite stereospecificity: the (E) alkene reacted with retention and the (Z) alkene with inversion of stereochemistry with respect to both the allylic stereocenter and the alkene geometry. Thus, a single gamma-substituted ester was obtained as the overall product, in high isomeric purity. The method was applied to a synthesis of a subunit of the iejimalides, a group of cytotoxic macrolides.

The crystal structure determination of the title compound, C12H20O2, is part of a model study carried out to investigate the chemistry related to our ongoing efforts toward the total synthesis of the zoanthamine alkaloids. The cyclo­hexene ring adopts a half-chair conformation. In the crystal structure, the mol­ecules are linked by inter­molecular O—H⋯O hydrogen bonds between the hydroxyl groups of neighbouring mol­ecules, forming columns parallel to the b axis.

The lethal effects of Africanized honey bee venom depend on the absorption of venom delivered during simultaneous sting attacks by large numbers of bees. The hypothesis that antibodies to whole bee venom and bee venom components could neutralize the lethal effect of bee venom was tested. Antibodies from beekeepers and immunized rabbits were incubated with bee venom and neutralization was studied by survival of intravenously injected mice. Beekeeper serum antibodies were found effective in protecting mice challenged with whole venom, and serum from rabbits immunized with phospholipase A2 (PLA2) was effective in protection against lethal effects of PLA2. Serum antibodies from rabbits immunized with whole venom or melittin were ineffective in neutralizing whole venom in vivo and had low titers in a venom enzyme-linked immunosorbent assay. The results suggest the need for development of more effective methods for raising antitoxic antibodies to bee venom components in other animals as a means of developing an antiserum that would be effective for treatment of human victims of multiple bee stings.

Purpose: To compare the presence of fibrosis through footplate positioning holes in two different silicone intraocular lenses (IOLs) following phacoemulsification with IOL implantation. Setting: Moran Eye Center, University of Utah, Salt Lake City. Methods: Twelve New Zealand white rabbits had phacoemulsification with placement of a control silicone IOL in one eye and a study IOL with a larger positioning hole in the opposite eye. The amount of force required to remove the IOLs from the capsular bag was analyzed at 3 and 6 weeks postoperatively. Results: The force necessary to remove the study lens with the larger positioning holes was statistically significantly greater at both 3 and 6 weeks than that necessary to remove the control lenses. Capsular fibrosis with proliferative lens cortical material through the larger positioning holes was also documented grossly using the Miyake technique. Conclusion: The larger footplate positioning holes in the study silicone IOL significantly increased capsular bag fixation in the rabbit model following phacoemulsification and IOL implantation.

Publisher Summary The use of palladium in organic synthesis has undergone a remarkable expansion in recent years. Many versatile synthetic methods have been developed and palladium is now the transition metal most frequently used in organic transformations. The reason for this rich chemistry is that palladium is highly efficient in almost all fundamental organometallic reactions, particularly those involving activation of organic substrates, and those leading to formation of new carbon–carbon and carbon–heteroatom bonds. This chapter focuses on the use of palladium-catalyzed reactions in the synthesis of alkaloids, but a few examples where palladium is used in stoichiometric amounts have also been presented in the chapter. The chapter describes a number of palladium-catalyzed processes that are often used in organic synthesis. These techniques can be conveniently divided into palladium(O) and palladium(II)-catalyzed reactions. In palladium(O)-catalyzed reactions the zerovalent metal is stabilized by ligands, most commonly by tertiary phosphines. Several different types of Pd(O)-catalyzed reactions are described in the chapter.

The Heidelberg Basin (HB) is a part of the Upper Rhine Graben that has undergone very strong subsidence throughout its existence. We present the first results of three-dimensional structural modelling of the basin, based on interpretation of reflection seismics, and decompaction based on our own porosity data measured from core material. Firstly, we mapped six horizons from all available industrial (ca. 100 km) and our own reflection seismic sections (ca. 15 km), which lie within a 8 km radius around the Heidelberg Uni-Nord 1/2 boreholes. We interpret these horizons as Base Quaternary, Internal and Base Pliocene, Base Upper Miocene, Internal and Base Mid Miocene Hydrobien beds.

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The thermal 1,5-hydrogen shift of the enantiomerically pure vinyl aziridines 1 yields allylic imines 3 in quantitative yields and as single diastereomers.

To determine if clarithromycin monotherapy is safe and effective in treating cutaneous disease (especially disseminated disease) due to Mycobacterium chelonae (formerly M. chelonae subspecies chelonae).An open, noncomparative trial of clarithromycin as single-drug therapy.Nationwide referrals.Culture-positive patients whose M. chelonae came from a cutaneous source and whose isolate was submitted to a single referral laboratory for susceptibility testing.Clarithromycin, 500 mg twice a day by mouth for 6 months. No attempt was made to alter use of immunosuppressive drugs.Acid-fast bacilli smears and cultures of skin lesions during and after treatment, with monitoring of clinical response, side effects, and development of new lesions.Fourteen patients (10 with disseminated disease) were enrolled in the study and completed at least 3 months of therapy. Underlying diseases included rheumatoid arthritis, other autoimmune disorders, and organ transplantation. All were taking corticosteroids (93%) or cyclophosphamide (7%). All patients had an excellent response to therapy, with only mild side effects from the drug. Two patients died of other diseases after improving clinically but while still taking medication. One noncompliant patient who prematurely discontinued therapy after 3.5 months relapsed 1 month later with an isolate resistant to clarithromycin. The remaining 11 patients have all completed therapy given for a mean of 6.8 months (range, 4.5 to 9 months). Therapy has been discontinued for 9 of the 11 patients for at least 6 months (mean, 7.1 months; range, 6 to 12 months), with no evidence of relapse. No remaining patient had positive acid-fast bacilli smears or cultures of skin lesions after 1 month of therapy.Clarithromycin may be the drug of choice for cutaneous (disseminated) disease due to M. chelonae, although more patients with long-term clinical follow-up need to be studied.

A short enantioselective synthesis of the spirocyclic alkaloid (+)-Nitramine ( 1 ) is reported, the azaspiro ring system being formed via intramolecular ring-opening of the chiral epoxy sulfone 7 .

The conformations and dynamic processes in two bicyclophanes have been analysed on the basis of temperature-dependent 1H NMR spectra. Both bicyclophanes are suggested to have a lowest-energy conformation of D3 symmetry in which the substituents at all ethylene bridges are gauche+ (or gauche−) oriented. The interconversion of the mirror image conformers of each bicyclophane equilibrates the two hydrogens in each methylene group, the barriers being ca 36 and 37 kJ mol−1, respectively, as determined by line-shape analysis.

An efficient enantioselective total synthesis of the antibiotic (+)-negamycin is described, the absolute stereochemistry deriving from ( R )-(+)-malic acid and subsequent use of the Sharpless asymmetric epoxidation reaction.

N-tosyl amides and lactams can be prepared easily and under mild conditions by the inter- or intramolecular condensation of carboxylic acids and secondary sulfonamides. The coupling reagent used is dicyclohexyl-carbodiimide (DCC) in the presence of 4-pyrrolidinopyridine (4-PPY) and the reactions proceed readily, usually in high yield, at room temperature.

The title compound has been synthesised by a reductive coupling of bibenzyl-4,4′- dicarbaldehyde and its dynamic properties and photoinduced isomerisations are briefly described.

On prepare les composes du titre par double ou triple reaction de Wittig suivie d'une copulation reductrice de dialdehydes

The molecular structure and dynamic behaviour of the bridged [4n] annulene 1,6:9,14-bismethano-[16]annulene is unravelled by NMR and X-ray investigations, combined with force field calculations.

An enantioselective synthesis of the carbapenem antibiotic (+)-PS-5 is described. The starting point is the chiral Sharpless epoxy-alcohol 3 which is transformed stereospecifically to the aziridine 6 . Regioselective ring-opening of 6 by LiEt2Cu followed by RuO4 oxidation yields the β-sulfonamido carboxylic acid 8 which is cyclised under mild conditions and in excellent yield to the N-tosyl azetidinone 9 . Deprotection at nitrogen, unmasking of the side-chain hydroxyl and oxidation then furnishes 11 , a known advanced intermediate for (+)-PS-5.

Limited space permits description of only two examples of Kevlar applications research. There are numerous others. In the early product development there were some indications that Kevlar would go mainly into tire reinforcement. This has turned out not to be true. In the mid-seventies Kevlar was participating in only ten market segments and less than fifty specific applications, but today, it is in more than twenty market segments, serving more than two hundred applications, and continued growth is anticipated. Kevlar is produced in a 45 million pound plant in Richmond, VA, USA. In 1988, a second plant was started up in Northern Ireland and plans for a third plant in Japan were announced. The Kevlar innovation story exemplifies the kind of obstacles, interdisciplinary skills and systems approach involved in bringing a laboratory discovery to commercial reality. The story is still unfolding and applications currently not envisioned will undoubtedly become important in the future. .

The title compounds, 1 and 1 ', are readily available in four steps from 2-benzyloxymethyl-2-propen-1-ol, the key step being Sharpless asymmetric epoxidation to give the chiral epoxides 5 or 5 '. The total chemical yield of 1 or 1 ' is 50%, the final products being obtained essentially optically pure. By suitable protecting group manipulation, both title enantiomers can be produced from either of the antipodal epoxides 5 or 5 '.

Reductive coupling of cychoheptatriene-1,6-dialdehyde using a low-valent titanium reagent provides a one-step route to a paratropic bismethano [16] annulene.

Two simple, efficient and stereocontrolled routes to the cis -azaspiro-[5-5]-undecan-8-ol skeleton of the histrionicotoxin alkaloids are described.

The title ketone has been synthesised in 96% e.e. from the corresponding methyl ester and MeLi. The [α]D value for the product was considerably higher than values previously reported for the enantiomer.

Three cyclophanes, each displaying a different type of dynamic process, have been studied by NMR methods. The barriers to these processes are attributed mainly to the decrease in π-electron overlap between the benzene rings and adjacent double bonds which occurs in the transition state for each process. In [5 2 ] paracyclophanetetraene, two successive flippings of the benzene rings interconvert the two hydrogens in the methylene groups (Scheme 1). In tetramethyl [2 4 ] paracyclophanetetraene, the passage of one methyl group through the central cavity of the molecule interconverts two conformations of similar, but not equal, free energy (Scheme 2). In [2 6 ] orthoparacyclophanehexaene, the orthosubstituted rings change sides by passing through the centre of the cyclophane (Scheme 3).

The structure and dynamic stereochemistry of a novel paracyclophane formed by electrocyclic ring closure of a hexatriene-bridged precursor are described.

An enantioselective total synthesis of the 14-membered macrolide antibiotic ingramycin, 1 , is described. In a convergent approach three chiral fragments A , B and C are assembled, the allylic bromide A deriving its chirality from L -serine while the asymmetric centres in sulfones B and C are introduced via the Sharpless enantioselective epoxidation technique. After coupling of these fragments and a highly efficient macrolactonisation (82% yield) a final deprotection step furnishes the target compound.

Two stereocontrolled routes to the alkaloid depentylperhydrohistrionicotoxin 3 , are described. The key steps are alkylation, with retention of configuration, of the iodide 8 and the mesylate 12 , respectively. A tricyclic aziridinium species is proposed as the reactive intermediate in the latter reaction. The synthesis of 3 represents a formal total synthesis of the title alkaloid.

L'alcaloide spiranique du titre est synthetise regio-, stereo- et chimioselectivement a partir de l'ether de benzyle et de cyclohexadiene-1',2'yl-4 butyle via des reactions catalysees par Pd(OH) 2 ou Pd(O Ac) (Ac=acetyl)

A short and completely stereocontrolled total synthesis of the title alkaloid is described, the key step being spirocyclisation of the epoxy sulfone 4 .