Efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). Methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. The limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.

http://science.sciencemag.org/content/sci/254/5037/1471.full.pdf

The atom economy--a search for synthetic efficiency

Metal-catalyzed cycloisomerization reactions of 1,n-enynes have appeared as conceptually and chemically highly attractive processes as they contribute to the highly demanded search for atom economy and allow the discovery of new reactions. Since the pioneering studies with palladium by the research group of Barry Trost in the mid-1980s, several other metals have been identified as excellent catalysts for the rearrangement of enyne skeletons. Moreover, the behavior of 1,n-enynes may be influenced by other functional groups such as alcohols, aldehydes, ethers, alkenes, or alkynes, thus enhancing the molecular complexity of the synthesized products. Apart from the intrinsic rearrangements of 1,n-enynes, several tandem reactions incorporating intramolecular trapping agents or intermolecular partners have been discovered. This Review aims to highlight the main contributions in this field of catalysis and to propose and comment on the mechanistic insights of the recent discoveries.

Cycloisomerization of 1,n-enynes: challenging metal-catalyzed rearrangements and mechanistic insights.

Cyclic carbopalladation. a versatile synthetic methodology for the construction of cyclic organic compounds

Cyclizations of N-acyliminium ions.

Die Effizienz der Synthese komplexer organischer Verbindungen zu steigern gehort zu den reizvollsten Aufgaben fur Synthesechemiker. Als erster Schritt hierzu ist die Entwicklung einer grosen Zahl einfacher Additionsreaktionen und die Minimierung von Abfallprodukten erforderlich. Im Brennpunkt solcher Forschungen stehen Ubergangsmetallkomplexe, die durch Anderung des Metalls und/oder der Liganden sowohl elektronisch als auch sterisch an die jeweiligen Erfordernisse exakt angepast werden konnen. Mit Ausnahme der katalytischen Hydrierung sind solche Methoden in komplexen Synthesen selten angewendet worden und waren fur CC-Verknupfungen bis zur Entwicklung der Kreuzkupplungen nahezu unbekannt. Ubergangsmetallkomplexe konnen an einer Vielzahl von CC-Bindungsbildungen beteiligt sein, die fur den Aufbau der Grundgeruste organischer Verbindungen von Bedeutung sind. Ihre Fahigkeit, sich in CH-Bindungen einzuschieben, ist Grundlage zahlreicher Additionsreaktionen an relativ unpolare π-Elektronensysteme. Sie ermoglichen nicht nur selektivere Reaktionen, sondern auch unkatalysiert nicht bekannte. Auf der Fahigkeit dieser Komplexe, π-Elektronensysteme zu praorganisieren, beruhen sowohl einfache Additionen, die im allgemeinen mit anschliesenden Wasserstoffverschiebungen einhergehen, als auch Cycloadditionen. Die Bildung „reaktiver” Zwischenstufen unter milden Bedingungen stellt auserdem neue Arten von CC-Verknupfungen in Aussicht. Auch wenn hier eine Vielzahl erfolgreicher neuer Reaktionen vorgestellt wird, sind die Moglichkeiten fur neue Entdeckungen enorm und bei weitem noch nicht ausgeschopft.

Atomökonomische Synthesen – eine Herausforderung in der Organischen Chemie: die Homogenkatalyse als wegweisende Methode

Synthesis of optically active pyrrolizidinediols: (+)-heliotridine

Unusual substituent effect on a palladium-mediated cyclization: a total synthesis of (.+-.)-sterepolide

We have studied a model compound for oxyhemoglobin and oxymyoglobin, the iron-dioxygen complex of \"picket fence porphyrin\" (5,10,15,20-tetrakis(a,a,a,~-~pivalamidophenyl)porphyrinato)iron (11) (( 1-MeIm)O,), as well as oxymyoglobin and oxyhemoglobin themselves, by using 170 solid-state nuclear magnetic resonance spectroscopy. For the model picket fence porphyrin, the principal components of the chemical shift tensors for both bridging and terminal oxygens in the Fe-0, unit have been determined, and the isotropic chemical shifts occur at 1200-1600 and 2000 ppm, respectively, somewhat deshielded from the 1750 and -2500 ppm values found by Gerothanassis et al. in solution (J. Am. Chem. Soc. 1989, I l l , 7006-7012). The anisotropies of the shift tensors are very large for both oxygens (A8 = -2200 ppm for the bridging oxygen and A6 = 3350 ppm for the terminal oxygen, at 77 K). From partial averaging of the shift tensors at room temperature, due to fast axial rotation of the dioxygen ligand, an Fe-O-O bond angle of 140' has been derived for the model system. Temperature dependence studies indicate essentially no change in the isotropic chemical shift of the terminal oxygen down to 4.2 K, while there is an apparent low-frequency shift of the bridging oxygen on cooling to 77 K, possibly due to the freezing in of one conformational substate. Spectra of oxymyoglobin and oxyhemoglobin, at 77 K, are very similar to those of the model compound at low temperature. Our results indicate that the 170 nuclear quadrupole coupling constants must be relatively small for both oxygens ( 5 5 MHz) in all systems, much smaller than the 8.5and 20-MHz values found for ozone, suggesting extensive *-delocalization in the Fe-0-0 fragment. Our results are also consistent with an overwhelmingly spin paired configuration, both in the model system, and in oxyhemoglobin and oxymyoglobin themselves.

Solid-State Oxygen-17 Nuclear Magnetic Resonance Spectroscopic Studies of [17O2] Picket Fence Porphyrin, Myoglobin, and Hemoglobin

We have obtained 1H and 13C magic-angle sample-spinning (MAS) nuclear magnetic resonance (NMR) spectra of three glycosyldiacylglycerol-water (1:1, weight ratio) mesophases, at 11.7 T, as a function of temperature, in order to probe lipid headgroup, backbone, and acyl chain dynamics by using natural-abundance NMR probes. The systems investigated were monogalactosyldiacyldiglyceride [MGDG; primarily 1,2-di[(9Z,12Z,15Z)octadec-9,12,15-trienoyl++ +]-3-beta-D-galactopyranosyl- sn-glycerol]; digalactosyldiacyldiglyceride [DGDG; primarily 1,2-di[(9Z,12Z,15Z)octadec-9,12,15-trienoyl++ +]-3- (alpha-D-galactopyranosyl-1-6-beta-D-glactopyranosyl)-sn-glycerol] ; and sulfoquinovosyldiacyldiglyceride [SQDG; primarily 1-[(9Z,12Z,15Z)octadec-9,12,15-trienoyl]-2 -hexadecanoyl-3-(6-deoxyl-6- sulfono-alpha-D-glucopyranosyl)-sn-glycerol]. At approximately 22 degrees C, all three lipid-water systems give well-resoled 13C and 1H MAS NMR spectra, characteristic of fluid, liquid-crystalline mesophases. 13C spin-lattice relaxation times of the headgroup and glycerol backbone carbons of all three materials give, within experimental error, the same NT1 values (approximately 400 ms), implying similar high-frequency motions, independent of headgroup size and charge. Upon cooling, pronounced line broadenings are observed, due to an increase in slow motional behavior. For each lipid, the onset of line broadening is seen with the glycosyl headgroup, glycerol backbone, and the first two or three carbons of the acyl chains. By approximately -20 degrees, all headgroup carbon resonances are broadened beyond detection. Both galactose moieties in DGDG "freeze out" together, implying a rigid-body motion of the disaccharide unit. Upon further cooling, the bulk polymethylene chain resonances in all three systems (in both 13C and 1H MAS) broaden greatly, followed by the olefinic and allylic carbon resonances.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectroscopic studies of lipids and biological membranes: carbon-13 and proton magic-angle sample-spinning nuclear magnetic resonance study of glycolipid-water systems.

We have obtained proton-coupled carbon-13 nuclear magnetic resonance (NMR) spectra of a variety of lipid-water and lipid-drug-water systems, at 11.7 T, as a function of temperature, using the "magic-angle" sample-spinning (MAS) NMR technique. The resulting spectra show a wide range of line shapes, due to interferences between dipole-dipole and dipole-chemical shielding anisotropy interactions. The differential line-broadening effects observed are particularly large for aromatic and olefinic (sp2) carbon atom sites. Coupled spectra of the tricyclic antidepressants desipramine and imipramine, in 1,2-dimyristoyl-sn-glycero-3-phosphocholine-water mesophases, show well-resolved doublets having different line shapes for each of the four aromatic methine groups, due to selective averaging of the four C-H dipolar interactions due to rapid motion about the director (or drug C2) axis. 2H NMR spectra of [2,4,6,8-2H4]desipramine (and imipramine) in the same 1,2-dimyristoyl-sn-glycero-3-phosphocholine-water mesophase exhibit quadrupole splittings of approximately 0-2 and approximately 20 kHz, indicating an approximate magic-angle orientation of the C2-2H(1H) and C8-2H(1H) vectors with respect to an axis of motional averaging, in accord with the 13C NMR results. Selective deuteration of imipramine confirms these ideas. Spectra of digalactosyl diglyceride [primarily 1,2-di[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl ]-3- (alpha-D-galactopyranosyl-1-6-beta-D-galactopyranosyl)-sn-glycerol]-H2O (in the L alpha phase) show a large differential line broadening for C9 but a reduced effect for C10, consistent with the results of 2H NMR of specifically 2H-labeled phospholipids [Seelig, J., & Waespe-Saracevic, N. (1978) Biochemistry 17, 3310-3315].(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon-13 nuclear magnetic resonance spectroscopy of lipids: differential line broadening due to cross-correlation effects as a probe of membrane structure

John Chung

Papers

Synthesis of optically active pyrrolizidinediols: (+)-heliotridine

Unusual substituent effect on a palladium-mediated cyclization: a total synthesis of (.+-.)-sterepolide

Solid-State Oxygen-17 Nuclear Magnetic Resonance Spectroscopic Studies of [17O2] Picket Fence Porphyrin, Myoglobin, and Hemoglobin

Spectroscopic studies of lipids and biological membranes: carbon-13 and proton magic-angle sample-spinning nuclear magnetic resonance study of glycolipid-water systems.

Carbon-13 nuclear magnetic resonance spectroscopy of lipids: differential line broadening due to cross-correlation effects as a probe of membrane structure