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Cyclization Step (cyclization + step)
Selected AbstractsThe Effect of Ring Size on Catenane SynthesisEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 17 2003Stefan Duda Abstract The synthesis of a [2]catenane with 87-membered rings was improved and extended to [2]catenanes with 63- and 147-membered rings. One of the key features is the carbonate linkage between phenols with tolane substituents in the 2- and 6-positions, which serves as a covalent template for the geometrical arrangement of a macrocycle and a ring precursor. Subsequent cyclization of the threaded ring precursor gives the precatenane as the main product, and this is converted into the catenane by carbonate hydrolysis. As well as the precatenane, its dumbbell shaped isomer is formed in the cyclization step. From the known conformation of the templating carbonate moiety and the strong dependence of the ratio of precatenane and dumbbell on the ring size, the dumbbell's origin is attributed to the conformational flexibility of the large rings and not to geometrical ambiguity of the carbonate moiety. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Diverse Asymmetric Quinolizidine Synthesis: A Stereodivergent One-Pot ApproachADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 2-3 2010Wei Zhang Abstract A diverse stereodivergent organocatalytic one-pot addition/cyclization/annulation sequence to optically active quinolizidine derivatives from easily available starting materials is presented. The one-pot sequence relies on a pyrrolidine-catalyzed enantioselective conjugate addition of electron-deficient amide ,-carbons to ,,,-unsaturated aldehydes, spontaneous hemiaminal formation and acid-catalyzed/mediated N -acyliminium ion cyclization to give the quinolizidine framework. Simple tuning of the reaction conditions in the N -acyliminuim ion cyclization step provides a diastereomeric switch, which gives access to both of the two bridgehead epimers through kinetic, thermodynamic or chelation control. The methodology display a broad substrate scope that is demonstrated by the stereoselective formation of indolo-, thieno-, benzofuro-, furo- and different benzoquinolizidine derivatives with high atom efficiency, up to >99% ee and up to >95:5 dr. Due to its efficiency, synthetic diversity and operational simplicity, this protocol has the potential to find important use as a key step in natural product synthesis, biochemistry and pharmaceutical science. The stereochemical outcome of the one-pot sequence was investigated, and the mechanism and origin of stereoselectivity of the different steps is discussed. [source] Synthesis of 14C-labeled piperidines and application to synthesis of [14C]SCH 351125, a CCR5 receptor antagonistJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 7 2007Sumei Ren Abstract 1-Benzyl-4-hydroxy[2- 14C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [14C]formaldehyde in high yield. The distribution pattern of 14C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza-Cope rearrangement. These steps precede the rate-determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [14C]SCH 351125, required for metabolism studies, was prepared from 1-benzyl-4-hydroxy[2- 14C]piperidine in six steps. [14C]SCH 351125 is a mixture of four atropisomers. Preparation of [14C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd. [source] Solution, solid phase and computational structures of apicidin and its backbone-reduced analogsJOURNAL OF PEPTIDE SCIENCE, Issue 6 2006Michael Kranz Abstract The recently isolated broad-spectrum antiparasitic apicidin (1) is one of the few naturally occurring cyclic tetrapeptides (CTP). Depending on the solvent, the backbone of 1 exhibits two ,-turns (in CH2Cl2) or a ,-turn (in DMSO), differing solely in the rotation of the plane of one of the amide bonds. In the X-ray crystal structure, the peptidic COs and NHs are on opposite sides of the backbone plane, giving rise to infinite stacks of cyclotetrapeptides connected by three intermolecular hydrogen bonds between the backbones. Conformational searches (Amber force field) on a truncated model system of 1 confirm all three backbone conformations to be low-energy states. The previously synthesized analogs of 1 containing a reduced amide bond exhibit the same backbone conformation as 1 in DMSO, which is confirmed further by the X-ray crystal structure of a model system of the desoxy analogs of 1. This similarity helps in explaining why the desoxy analogs retain some of the antiprotozoal activities of apicidin. The backbone-reduction approach designed to facilitate the cyclization step of the acyclic precursors of the CTPs seems to retain the conformational preferences of the parent peptide backbone. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Preparation of cyclic peptide libraries using intramolecular oxime formationJOURNAL OF PEPTIDE SCIENCE, Issue 11 2004Dr Kade D. Roberts Abstract A new method for the synthesis of cyclic head-to-side chain peptide libraries has been developed in which the key cyclization step involves reaction between a C -terminal ketone and an N -terminal hydroxylamine to form a macrocyclic oxime. This methodology efficiently delivers cyclic products that consist of mixtures of syn and anti isomers. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Macrocyclic Hexaureas: Synthesis, Conformation, and Anion BindingCHEMISTRY - A EUROPEAN JOURNAL, Issue 19 2009Denys Meshcheryakov Dr. Abstract Varied flexibility: Cyclic oligoureas are formed by using anions as templates. Linking of six xanthene and/or diphenyl ether fragments by urea groups leads to the formation of five macrocyclic compounds with a 48-membered ring with variable flexibility (see picture). Their interaction with anions shows a strong influence of acetate and chloride ions on the cyclization from four precursor molecules. Five macrocylic compounds XXXXXX, XXDXXD, XDXDXD, XDDXDD, and DDDDDD with 48-membered rings, in which six xanthene and/or diphenyl ether fragments are linked through six urea (-NH-C(O)-NH-) groups, have been synthesized. In the cyclization step, a linear diamine was allowed to react with the appropriate diisocyanate by using a [5+1] (i.e., "XDXDX+D" for XDXDXD), [4+2] (DDDDDD), or [3+3] (XDDXDD) procedure. Compounds XXXXXX and XXDXXD were prepared from two molecules of the dimeric amine XX and two molecules of the respective monomeric diisocyanate (X or D) in a [2+1+2+1] (or 2×[2+1]) reaction. The (nonoptimized) yields in the cyclization step ranged from 45 to 80,%. The linear precursor diamines or diisocyanates were obtained by analogous condensation reactions by using partial protection with a tert -butoxycarbonyl group. All the macrocyclic compounds and synthetic intermediates were characterized by 1H,NMR and mass spectra. Three different crystal structures were obtained for XDDXDD, which show the molecule in a more or less strongly folded conformation determined by intramolecular hydrogen bonding. The interaction of the hexaureas with selected anions was studied by 1H,NMR spectroscopy and UV absorption spectrophotometry. [source] From Metacyclophanes to Cyclacenes: Synthesis and Properties of [6.8]3CyclaceneCHEMISTRY - A EUROPEAN JOURNAL, Issue 14 2009Birgit Esser Dr. Abstract Conjugated belts: [6.8]3cyclacene as the first hydrocarbon cyclacene was synthesized in a de novo strategy. Various [23]metacyclophanes are described as intermediates. The synthetic approach was extended to larger cyclacenes, and [24]metacyclophanes as precursors of [6.8]4cyclacene were synthesized. In this article we show synthetic pathways to [6.8]ncyclacenes demonstrated by the de novo synthesis of [6.8]3cyclacene as the first purely hydrocarbon cyclacene and of precursors for [6.8]4cyclacene. The design of the de novo synthesis by exploring alternative pathways is discussed and various precursors are shown. Crucial to the synthesis of [6.8]3cyclacene were two cyclization steps. The first is a Wittig trimerization reaction which yielded the hexamethyl substituted all - cis -[23]metacyclophanetriene. For the second cyclization step the methyl groups were converted to aldehyde functionalities by two subsequent oxidation steps of N-bromosuccinimide (NBS) bromination and oxidation with 2-iodoxybenzoic acid (IBX). The final cyclization of the second set of double bonds was achieved by a McMurry-coupling reaction. Towards the synthesis of [6.8]4cyclacene different synthetic pathways to methyl substituted all - cis -[24]metacyclophanetetraenes were explored. Insights into the structures of [23]metacyclophanetri- and [24]metacyclophanetetraenes were gained by X-ray crystallographic investigations on various intermediates. A crystallographic analysis of [6.8]3cyclacene revealed a D3h symmetrical structure with planar benzene rings and a formation of tubular structures in the solid state. [source] | ||||||||||