Transition metal catalyzed C-C bond formations belong to the most important reactions in organic synthesis. One particularly interesting reaction is olefin metathesis, a metal-catalyzed exchange of alkylidene moieties between alkenes. Olefin metathesis can induce both cleavage and formation of C-C double bonds. Special functional groups are not necessary. Although this reactionwhich can be catalyzed by numerous transition metals-is used in industry, its potential in organic synthesis was not recognized for many years. The recent abrupt end to this Sleeping-Beauty slumber has several reasons. Novel catalysts can effect the conversion of highly functionalized and sterically demanding olefins under mild reaction conditions and in high yields. Improved understanding of substrate -catalyst interactions has greatly contributed to the recent establishment of olefin metathesis as a synthetic method. In addition to the preparation of polymers with fine-tuned characteristics, the metathesis today also provides new routes to compounds of low molecular weight. The highly developed ring-closing metathesis has been proven to be a key step in the synthesis of a growing number of natural products. At the same time interesting applications can be envisioned for newly developed variants of bimolecular metathesis. Improvements in the selective cross-metathesis of acyclic olefins as well as promising attempts to include alkynes as viable substrates provide for a vivid development of the metathesis chemistry.

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COMMUNICATIONSoxidative addition of 1 to the Pto complex, ["] followed by reductive elimination of diborane (Scheme 4). Formation of D could be suppressed by using [Pt(PPh,),] as a catalyst, that is, in the presence of excess PPh,. 1 A -LnP/ SIR', D Scheme 4. Possible route of formation of a bis(sily1)platinum complexThe silaboration reaction made possible a regioselective C-C bond formation at the boryl-substituted C atom. For example, one-carbon homologation of 2 a and 5, prepared from 1 -octene and 1-octyne, respectively, was carried out (Scheme 5). Treatment of 2a and 5 with chloro(trimethy1silyI)methyllithium gave the corresponding homologation products 6 and 7, respectively, after selective removal of the trimethylsilyl group by tetrabutylammonium fluoride (TBAF) .["] SiMqPh a,b 74% 2a -Hex 0, .o PhMe Si uB a,b 72% Hex 5 -7 Scheme 5. Synthesis of 6 and 7: a) Me,SiCH,Cl, sBuLi, N,N,N',N'-tetramethyl ethylene diamine, THF, -78°C b) TBAF, THF, reflux.Here we have presented preliminary results on the regioselective silaboration of simple alkenes. Optimization of the reaction conditions on the basis of the mechanism shown in Scheme 3 is currently underway. Experimental SectionGeneral procedure for silaboration of alkenes: To a solution of platinum catalyst (0.076 mmol) in dioxane (1 mL) were added silylborane 1 (3.9 mmol) and alkene (5.9 mmol). The mixture was heated at reflux for 2 h. Evaporation of volatile materials under reduced pressure was followed by column chromatography on silica gel to give 2 and 3 in the yields listed in Tables 1 and 2.

Übergangsmetallkatalysierte C‐C‐Verknüpfungen gehören zu den wichtigsten Reaktionen in der organischen Synthese. Eine interessante Reaktion aus dieser Klasse ist die Olefinmetathese, ein metallkatalysierter Austausch von Alkylidengruppen zwischen Olefinen. Die Olefinmetathese ermöglicht die Spaltung und Knüpfung von C‐C‐Doppelbindungen. Besondere funktionelle Gruppen sind dabei nicht erforderlich. Obwohl die durch eine Vielzahl von Übergangsmetallen katalysierte Reaktion industriell genutzt wird, lag ihr Potential für die organische Synthese lange Zeit weitgehend brach. Daß dieser Dornröschenschlaf vor kurzem ein jähes Ende fand, hat mehrere Gründe. So ermöglichen neue Katalysatoren die Umsetzung hochfunktionalisierter und sterisch anspruchsvoller Olefine unter milden Reaktionsbedingungen und in hohen Ausbeuten. Ein verbessertes Verständnis der Substrat‐Katalysator‐Wechselwirkungen hat wesentlich dazu beigetragen, daß sich die Olefinmetathese derzeit als Synthesemethode etabliert. Außer der Herstellung von Polymeren mit maßgeschneiderten Eigenschaften eröffnet die Metathese heute auch neue Zugänge zu komplexen niedermolekularen Verbindungen. Die bereits hochentwickelte Ringschlußmetathese bewährt sich als Schlüsselschritt in der Synthese einer wachsenden Zahl von Naturstoffen. Zugleich zeichnen sich für neuentwickelte bimolekulare Metathesevarianten interessante Anwendungen ab. Fortschritte bei der selektiven gekreuzten Metathese acyclischer Olefine lassen ebenso wie vielversprechende Ansätze zur Einbeziehung von Alkinen eine weiterhin lebhafte Entwicklung der Metathesechemie erwarten.

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Abstractα-adrenergic receptors (αARs) are G protein-coupled receptors that regulate vital functions of the cardiovascular and nervous systems. The therapeutic potential of αARs, however, is largely unexploited and hampered by the scarcity of subtype-selective ligands. Moreover, several aminergic drugs either show off-target binding to αARs or fail to interact with the desired subtype. Here, we report the crystal structure of human α1BAR bound to the inverse agonist (+)-cyclazosin, enabled by the fusion to a DARPin crystallization chaperone. The α1BAR structure allows the identification of two unique secondary binding pockets. By structural comparison of α1BAR with α2ARs, and by constructing α1BAR-α2CAR chimeras, we identify residues 3.29 and 6.55 as key determinants of ligand selectivity. Our findings provide a basis for discovery of α1BAR-selective ligands and may guide the optimization of aminergic drugs to prevent off-target binding to αARs, or to elicit a selective interaction with the desired subtype.

This paper describes an efficient enzymatic procedure for the synthesis of phospholipid-inhibitor conjugates. The chemoselectivity, regioselectivity, and stereoselectivity of phospholipase-D-catalyzed phosphatidylations were investigated, and phospholipids containing inhibitors such as azasugars, nucleosides, and peptides were synthesized. These phospholipid conjugates in aqueous solution generally form liposome bilayers with multivalent inhibitors (the head groups) displayed on the surface and may find use in drug delivery and targeting. They also exhibit interesting structural features in different solvent systems as indicated in the NMR spectra.Liposome technology has provided a powerful tool for efficient drug delivery and targeting,' as a number of pharmaceuticals have been encapsulated in liposome forms2 or attached onto the surface of liposomes by a labile bond. Liposomes containing 2,3dipalmitoyl-sn-glycerol-1 -phospho-S'-azidot h ymidine, for example, showed a greatly enhanced inhibition of human immunodeficiency virus (HIV) replication in u i~r o .~.~ The liposomes with inhibitors displayed on the surface could either directly interact with the targeted surface receptors via a multivalent contact or serve as prodrugs for a sustained release of the inhibitor upon enzymatic hydrolysis in vivo (e.g., by cellular lipases and phospholipases)? As part of our interest in the development of new methods for the preparation of phospholipids, we describe here the study of phospholipase D (PLD, EC 3.1.4.4) for the synthesis of phospholipid-inhibitor conjugates.PLD catalyzes the hydrolysisof the terminal phosphate diester bond of glycerophospholipids to release phosphatidic acid.6 Previous studies showed that PLD catalyzed the transfer of the phosphatidyl group from phosphatidylcholine to primary alcoh0ls,7-~ but little was known regarding its synthetic utility. t Deutsche Forscbungsgemeinschaft Postdoctoral Fellow. Abstract published in Aduance ACS Abstracts, October IS, 1993. (1) Ostro, M. J.(3) Hostetler, K. Y.; Stahmiller, L. M.; Lenting, H. B. M.; Bosch, H. V. D.; Richman, D. D. J. Biol. Chem. 1990,265,6112. Wijik,G. M. T.;Gadella, T. W. J.; Wirtz, K. W. A.; Hostetler, K. Y.; Bosch, H. V. D. Biochemistry 1992.31 , 59 12. (4) Similar approaches have been publishad; see: Spevak, W.; Nagy, J. 0.; Charych, D. H.; Schaefer, M. E.; Gilbert, J. H.; Bednarski, M. D. Schubert, G.; Enhsen, A.; Baringhaus, K.-H.; Glombik, H.; Mullner, S.; Bock, K.; Kleine, H.; John, M.; Neckermann, G.; Hoffmann, A. Tetrahedron Left. 1993, 34.8 19. (5) Wijk,G.M.T.;Hostetler,K.Y.;Schlame,M.;Basch,H.(8) Shuto, S.; Imamura, S.; Fukukawa, K.; Sakakibara, H.; Murase, J. Chem. Pharm. Bull. 1987,35,447. Juneja, L. R.; Kazuoka, T.; Goto, N.; Yamane, T.; Shimizu, S. Biochim. Biophys. Acta 1989, 1003,277. Shuto, S.; Ucda, S.; Imamura, S.; Fukukawa, K.; Matsuda, A.; Ueda, T. Tetrahedron Leu. 1987,28, 199. Shuto, S.; Itoh, H.; Ueda, S.; Imamura, S.; Fukukawa, K.; Tsujino, M.; Matsuda, A.; Ucda, T. Chem. Pharm. Bull. 1988,36,209. FL, 1984; Val. 1-111. ...