Eight-membered ring templates for stereoselective radical cyclizations

Chemistry and Biology of Taxol

Abstract: One can view plants as a reference library of compounds waiting to be searched by a chemist who is looking for a particular property. Taxol, a complex polyoxygenated diterpene isolated from the Pacific Yew, Taxus brevifolia, was discovered during extensive screening of plant materials for antineoplastic agents during the late 1960s. Over the last two decades, interest in and research related to taxol has slowly grown to the point that the popular press now seems poised to scoop each new development. What was once an obscure compound, of interest only to the most masochistic of synthetic chemists and an equally small number of cellular biologists, has become one of the few organic compounds, which, like benzene and aspirin, is recognizable by name to the average citizen. In parallel, the scientific study of taxol has blossomed. Physicians are currently studying its effects on nearly every known neoplasm. Biologists are using taxol to study the mechanisms of cell function by observing the effects of its interactions with the cellular skeletal systems. Synthetic chemists, absorbed by the molecule's unique and sensitive structure and functionality, are exploring seemingly every available pathway for its synthesis. Indeed, the demand for taxol has risen so in the last five years that alternative sources to the extraction of T. brevifolia are being vigorously pursued. Because of the rapidly expanding scope of research in the multifaceted study of taxol, those who are interested in the field may find acquisition of a reasonable base of knowledge an arduous task. For this reason, this account attempts to bring together, for the first time, in a cogent overview the chemistry and biology of this unique molecule.

Free radicals in the synthesis of medium-sized rings

Abstract: Applications of free radical chemistry in the syntheses of seven- to nine-membered rings are presented in this review.

Chemie und Biologie von Taxol

Abstract: Die Pflanzen konnten als Quelle von Verbindungen betrachtet werden, aus denen sich der Chemiker solche mit besonderen Eigenschaften heraussuchen kann. Taxol, ein komplexes, polyoxygeniertes Diterpen aus der Pazifischen Eibe, Taxus brevifolia, wurde in den spaten sechziger Jahren bei einer umfassenden Untersuchung pflanzlicher Stoffe auf antineoplastische Wirkstoffe entdeckt. In den vergangenen zwei Jahrzehnten sind das Interesse an Taxol und die damit verbundenen Forschungsarbeiten langsam an dem Punkt angelangt, an dem es scheint, das die Medien aufmerksam geworden sind und jede neue Entwicklung gespannt erwarten. Das, was einstmals eine weitgehend unbekannte Verbindung war, an der nur die masochistischsten unter den Synthesechemikern und eine ebenso kleine Zahl von Zellbiologen Interesse zeigten, ist heute eine der wenigen organischen Substanzen, die — wie etwa Benzol oder Aspirin — auch dem Durchschnittsburger, dem Namen nach bekannt sind. Die wissenschaftlichen Untersuchungen von Taxol haben sich in dieser Zeit enorm ausgeweitet: Arzte erforschen zur Zeit seine Wirkung auf nahezu jedes bekannte Neoplasma; Biologen untersuchen die Wechselwirkungen zwischen Taxol und Zellskelettsystemen, um auf diese Weise die Mechanismen zu ergrunden, nach denen Zellen funktionieren; Synthesechemiker, die von der einzigartigen und empfindlichen Struktur sowie von der Funktionalitat des Taxols gefesselt sind, arbeiten intensiv daran, einen synthetischen Zugang zu ihm zu finden. Die Nachfrage nach Taxol ist in der Tat in den letzten funf Jahren so stark gestiegen, das intensiv nach Quellen alternativ zur Extraktion von T. brevifolia gesucht wird. Da bei den vielfaltigen Arbeiten uber Taxol der Wissensumfang schnell zunimmt, mag es fur den in diesem Gebiet Interessierten schwierig sein, sich ein angemessenes Grundwissen anzueignen. Wir wollen in diesem Beitrag daher erstmalig versuchen, einen Uberblick sowohl uber die Chemie als auch uber die Biochemie dieser einzigartigen Verbindung zu geben.

Radical Cyclization Reactions

Abstract: Radical cyclization reactions are among the most powerful and versatile methods for the construction of mono- and polycyclic systems. The advantages these reactions offer to the synthetic organic chemist include high functional group tolerance and mild reaction conditions combined with high levels of regio- and stereochemistry. Furthermore, the recent progress in radical chemistry has led to the development of a broad range of very useful practical methods to conduct radical cyclization reactions. In general, radical cyclization reactions comprise three basic steps: selective radical generation, radical cyclization, and conversion of the cyclized radical to the product. For the generation of the initial radical a broad variety of suitable precursors can be employed, such as halides, thio- and selenoethers, alcohols, aldehydes and hydrocarbons. The cyclization step usually involves the intramolecular addition of a radical to a multiple bond. Most often carbon–carbon multiple bonds are employed; however, there are also examples known for the addition to carbon–oxygen and carbon–nitrogen bonds. Depending on the method employed, the cyclized radical is converted to the desired product by trapping with a radical scavenger, by a fragmentation reaction, or by an electron transfer reaction. The section Mechanism, Regio- and Stereochemistry provides an introduction to the key features of radical cyclization with a special emphasis on the factors controlling the regio- and stereochemistry. The section Scope and Limitations covers the different methods used to conduct radical cyclization. The basic principles of radical chemistry and general practical considerations when conducting radical cyclizations are not discussed in detail. Several excellent review articles and books dealing with these topics are available. Keywords: radical cyclization reactions; mechanism; regiochemistry; steroechemistry; small rings; scope; limitations; medium-sized rings; formation; monocycles; macrocyclizations; bi-cycles; polycycles; metal hydride; tin hydride; mercury hydride; fragmentation methods; thiohydroxamine; methods; Barton method; atom transfer; hydrogen atom transfer; halogen atom transfer; radical/radical coupling; redox methods; sequential reactions; experimental conditions; experimental procedures; comparison of methods; tabular survey

Chemical consequences of conformation in macrocyclic compounds

Abstract: In this paper we show that the conformational properties of medium- and large-ring organic molecules have profound consequences on the stereochemical course of their chemical reactions. Kinetic enolate alkylations, dimethylcuprate additions and catalytic hydrogenations were examined on a variety of monosubstituted 8- to 12-membered macrocyclic ketones and lactones, and the diastereomeric composition of the products was determined. In many systems a single Me substituent provided enough conformational bias to allow highly stereoselective formation of new asymmetric centers. The diastereoselection exhibited by the reactions investigated appears to be intimately associated with the conformational properties of the macrocyclic substrates employed since simple molecular mechanics calculations allowed semiquantitative prediction of the product distributions in every case.