PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cyclization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources
PubMed1996

Synthesis of Trideca-O-methyl-alpha-pedunculagin. Diastereo-Favoritism Studies on Intramolecular Ester-Cyclization of Axially Chiral Diphenic Acids with Carbohydrate Core.

Total synthesis of trideca-O-methyl-alpha-pedunculagin was achieved by a simple sequence. The key step is the synthesis of methyl 4,6-O-benzylidene-2,3-O-[(S)-4,4',5,5',6,6'-hexamethoxydiphenoyl]-alpha-D-glucopyranoside through intramolecular ester-cyclization of racemic hexamethoxydiphenoyl chloride with methyl 4,6-O-benzylidene-alpha-D-glucopyranoside at the 2,3-position. The diastereoselectivity results obtained in the intramolecular cyclization of hexamethoxydiphenic acid to the carbohydrate core raises a very interesting point in considering the pathway of (R)-diphenic acid biosynthesis.

Journal Article↗
PubMed1996

Highly Stereoselective Cationic Cyclization Assisted by a Sulfenyl Group. Scope, Limitation, and Mechanism.

When 8-acetoxy-2-methyl-9-(phenylthio)-2-nonene (1a) was treated with an acid, followed by a base, alkylative cyclization proceeded to give a mixture of 1,2-disubstituted cyclohexanes: 2a, 3a, and 4a. The stereochemistry of the reaction was only slightly affected by the leaving group and the reaction conditions, such as the temperature, solvent, and acid. However, the bulkiness of the sulfenyl group had a great effect on the stereochemical course of the reaction. High trans selectivity was attained when 1c (a derivative of 1a with a bulkier sulfenyl group) was used as a substrate. On the other hand, the length and rigidity of the carbon chain of the substrate also had a major effect on the stereochemistry of the reaction; a high cis selectivity was observed when 10a (a one-carbon-fewer analog of 1a) or 15a (a derivative with one more double bond in the carbon chain than in 1a) was used as the substrate. The reaction proceeded via a 6,5- or 5,5-fused-ring intermediate. The sulfenyl-group-assisted reaction could be a useful method for the stereoselective cyclization of acetates of alpha-sulfenylated secondary alcohols.

Journal Article↗
PubMed1996

Reductions, Reductive Alkylations, and Intramolecular Cyclizations of Acyl Silanes with Samarium Diiodide or Tributyltin Hydride.

A series of acyl silanes including aliphatic-, aromatic-, and bis-acyl silanes, as well as the acyl silanes bearing other substituents such as a bromine atom and alkenyl, succinimide, and carbonyl groups, were prepared, and their reactions with samarium diiodide or tributylstannane were studied. The reactions of acyl silanes occurred in various manners such as reductions, reductive alkylations, intramolecular radical cyclizations, pinacol couplings, aldol reactions, and Tishchenko reactions, depending on the nature of substrates and reaction conditions. Acyl silanes were generally reduced to give the corresponding alpha-silyl alcohols without transfer of silyl groups. Intramolecular radical cyclizations of 5-hexenoyl silanes and 1-silyl-1,5-pentanedione were realized to give alpha-silyl cyclopentanols and 1,2-cyclopentanediol derivatives, respectively. On treatment with samarium diiodide in tetrahydrofuran, 1-(trimethylsilyl)-1,6-hexanedione underwent a pinacol coupling reaction in the presence of t-BuOH, whereas it underwent a Tishchenko reaction in the presence of MeOH. The Tishchenko reaction of 1-silyl-1,5-pentanedione gave a delta-silyl-delta-lactone. On treating with samarium diiodide, 1-(trimethylsilyl)-1,5-hexanedione and 1,5-bis(trimethylsilyl)-1,6-hexanedione, underwent, respectively, intramolecular aldol reactions.

Journal Article↗
PubMed1996

A Radical Cyclization Approach to Isoindolobenzazepines. Synthesis of Lennoxamine.

The alkaloid lennoxamine (1) was synthesized by transannular cyclization of a 10-membered lactam obtained by intramolecular addition of an aryl radical to a (trimethylsilyl)acetylene. The isoindolo[1,2-b][3]benzazepine skeleton present in lennoxamine was also obtained by means of regioselective 7-endo-trig radical cyclization of methylenephthalimidines.

Journal Article↗
PubMed1996

Synthesis of Tricyclic beta-Methylene Spiro Lactones Related to Bakkenolides by Successive Radical Cyclization-High Pressure Diels-Alder Reactions.

The synthesis of some novel bakkenolides and their epi-spiro analogues was achieved by a new approach. Photolysis of allyl 1-(phenylseleno)-2-oxocyclopentanecarboxylates 7-9 afforded the corresponding spiro lactones 10-12 by radical cyclization via group transfer of the phenylseleno group. Selenoxide elimination of 11 and 12 produced the corresponding beta-methylene lactones 14 and 15. Diels-Alder cycloaddition of lactone11 with piperylene failed at ambient pressure, but proceeded in generally good yield in the presence of various Lewis acids at pressures of ca. 16 kbar, to give mixtures of beta-exo, alpha-endo, and beta-endo cycloadducts 19, 21, and 23, respectively. The preponderance of endo products 21 and 23, formed via highly hindered, but more compact, transition states was attributed to the high pressure and resulted in trans-dimethyl configurations of the products. The facial selectivity was dependent upon the Lewis acids, and the greatest alpha:beta ratio was observed with catalysts of the type TiCl(2)(OR)(2). Epimerization of the C-4 methyl group in 21 and 23 to furnish the corresponding cis-dimethyl analogues was achieved via exo-epoxidation, regioselective reduction, oxidation to the corresponding 3-keto derivatives, and base-catalyzed equilibration, thereby affording (+/-)-3,6-dioxobakkenolide-A (39) and its epi-spiro derivative 28, respectively. When the radical cyclization step was performed subsequent to the Diels-Alder cycloaddition by photolysis of perhydrindane 43, only the epi-spiro product 44 was obtained.

Journal Article↗
PubMed1997

Utilization of the Intramolecular Cycloaddition-Cationic pi-Cyclization of an Isomünchnone Derivative for the Synthesis of (+/-)-Lycopodine.

A new annulation sequence leading to the tetracyclic skeleton of the Lycopodium family of alkaloids is effected by using the tandem cycloaddition-cationic pi-cyclization reaction of an isomünchnone dipole as the key strategic element. Synthesis of the required alpha-diazo imide precursor involved treating 5-methylcyclohex-2-en-1-one with the organocopper reagent derived from 3-methoxybenzyl chloride in the presence of chlorotrimethylsilane. Ozonolysis of the resulting silyl enol ether followed by a Wittig reaction and conversion to the desired alpha-diazo imide was carried out using standard malonylacylation and diazotization procedures. Treatment of the alpha-diazo imide with rhodium(II) perfluorobutyrate afforded a transient 1,3-dipole which subsequently cycloadded across the tethered pi-bond. The resulting cycloadduct was treated with BF(3).2AcOH to give a rearranged tetracyclic compound derived from a Pictet-Spengler-type cyclization of an N-acyliminium ion. The rearranged product was subsequently converted into a key intermediate previously used for the synthesis of (+/-)-lycopodine.

Journal Article↗
PubMed1999

Conformational Switching and the Synthesis of Spiro[2H-indol]-3(1H)-ones by Radical Cyclization.

Radical cyclization of 1-(2-bromophenylamino)cyclohexanecarbonitriles (3, X = CH) and 4-(2-bromophenylamino)-4-piperidinecarbonitriles (3, X = N) provide spiro[2H-indole-2-cyclohexan]-3(1H)-imines (5, X = CH) and spiro[2H-indole-2,4'-piperidin]-3(1H)-imines (5, X = N), respectively, in 33-57% yields. This contradicts a recent report that 1-(2-bromophenylamino)cyclohexanecarbonitrile (3, X-R(2) = CH(2)), treated under apparently identical conditions, led only to nitrile transfer product 6 (X-R(2) = CH(2)). Acidic hydrolyses of the imines provide the corresponding ketones 2 in quantitative yields. Single-crystal X-ray analyses of ketone 2e and nitrile 3e indicate that the relative configuration of the aromatic nitrogen has been inverted during the cyclization. In addition, NOE NMR analyses of spiroindolepiperidine 2c and its aniline-nitrogen-methylated analogue 10a show that the relative conformation of the piperidine ring has inverted. Thus, methylation of 2c acts as a conformational "switch" for the spiroindolepiperidine ring system.

Journal Article↗
PubMed1998

Intramolecular Cyclization of Azides by Iminium Species. A Novel Method for the Construction of Nitrogen Heterocycles under Vilsmeier Conditions.

An unprecedented attack of the azide functionality by iminium species, generated in situ under Vilsmeier conditions, provided a novel route for the construction of nitrogen heterocycles. Thus, the treatment of 2-azidoacetophenones with Vilsmeier reagent under reflux conditions gave 5-aryloxazole-4-carboxaldehydes. One-pot synthesis of oxazole carboxaldehydes from 2-bromoacetophenones by dehaloazidation-Vilsmeier cyclization reaction sequence provided better yields. The susceptibility of the carbonyl group to undergo chloroformylation at room temperature without affecting the azide function was exploited to provide an attractive scheme for the synthesis of alpha-azido-beta-chlorovinyl azides from phenacyl azides. The synthesis of a series of N-aryl 5-chloro-2-(dimethylamino)imidazole-4-carboxaldehydes was accomplished by the Vilsmeier cyclization of N-aryl-2-azidoacetamides. The possible mechanisms for the reactions are also discussed.

Journal Article↗
PubMed1999

4-Endo-Trig Cyclization Processes Using Bis(collidine)bromine(I) Hexafluorophosphate as Reagent: Preparation of 2-Oxetanones, 2-Azetidinones, and Oxetanes.

Reaction in methylene chloride of bis(collidine)bromine(I) hexafluorophosphate with alpha,beta-unsaturated acids and alpha,beta-unsaturated N-sulfonamides was found to lead diastereospecifically to the corresponding 2-oxetanones and 2-azetidinones in moderate yields (23-60%), by an almost unknown 4-endo cyclization. This process allow the synthesis of these interesting classes of products in one step from common substrates. Similarly, the reaction of cinnamic alcohols led, by the same cyclization procedure, to oxetanes (20-36%); the presence of a gem-dimethyl group in alpha of the alcohol function appeared beneficial.

Journal Article↗
PubMed1999

A Backbone Linker for BOC-Based Peptide Synthesis and On-Resin Cyclization: Synthesis of Stylostatin 1(,).

We have developed a new 4-alkoxybenzyl-derived linker that anchors the C-terminal amino acid to the resin through the alpha-nitrogen atom. The linker allows BOC solid-phase peptide assembly and peptide cleavage using standard HF protocols. This linking strategy provides a versatile on-resin route to cyclic peptides and avoids the diketopiperazine formation that is prominent when using FMOC chemistry on backbone linkers. The linker was prepared by forming the aryl ether from 4-hydroxybenzaldehyde and bromovaleric acid. Subsequent reductive amination of the aldehyde with an allyl-protected amino acid ester and acylation of the resulting secondary amine provided the tertiary amide. After linking the amide to the resin, standard BOC SPPS, followed by allyl deprotection, cyclization, and HF cleavage gave cyclic peptides in high purity. To exemplify the strategy, the cytotoxic heptapeptide, stylostatin 1, was synthesized from two linear precursors. For comparison purposes, the yields of the on-resin and solution-phase cyclization were determined and found to be dependent upon the linear precursor. This linker technology provides new solid-phase avenues in accessing libraries of cyclic peptides.

Journal Article↗
PubMed1999

Design and Preparation of 3,3'-Disubstituted 2,2'-Bis(oxazolyl)-1,1'-binaphthyls (boxax): New Chiral Bis(oxazoline) Ligands for Catalytic Asymmetric Wacker-Type Cyclization.

New optically active 2,2'-bis(oxazolyl)-1,1'-binaphthyls (boxax) bearing various substituents (methoxycarbonyl, trimethylsilyl, (dimethylamino)carbonyl, formyl, and iodo) at their C3 and C3' positions were prepared via ortho-lithiation promoted by the oxazolyl groups. The 3,3'-disubstituted boxax ligands showed much higher enantioselectivity than the 3,3'-unsubstituted ones in the palladium(II)-catalyzed Wacker-type cyclization of an o-allylphenol. The cyclization of (E)-2-(2-methyl-2-butenyl)phenol (10) in the presence of a cationic palladium catalyst coordinated with (S)-2,2'-bis(4,4-dimethyloxazol-2-yl)-3,3'-bis(methoxycarbonyl)-1,1'-binaphthyl gave (S)-2-ethenyl-2-methyl-2,3-dihydrobenzofuran of 96% ee.

Journal Article↗
PubMed1999

Studies on the Biosynthesis of the Fungal Metabolite Oudenone. 2. Synthesis and Enzymatic Cyclization of an alpha-Diketone, Open-Chain Precursor into Oudenone in Cultures of Oudemansiella radicata.

The alpha-diketone 4 was shown to be the open-chain biosynthetic precursor of the fungal metabolite oudenone (1a and 1b). Intact incorporation of 4 into 1 was achieved upon incubation of a (2)H-labeled, N-acetylcysteamine thioester derivative of 4 with growing cultures of Oudemansiella radicata. A biosynthetic scheme for the formation of the hexaketide 4 and its enzymatic cyclization into oudenone (1), consistent with the experimental data, is described. The proposed mechanism for the cyclization of 4 to 1 is analogous to the "polyepoxide cascade" model, which has been previously implicated in the biosynthesis of polyether antibiotics.

Journal Article↗
PubMed2000

Electrocyclic ring-opening/pi-allyl cation cyclization reaction sequences involving gem-dihalocyclopropanes as substrates: application to syntheses of (+/-)-, (+)-, and (-)-gamma-lycorane.

The readily prepared gem-dibromocyclopropanes (+/-)-13 and (+/-)-19 each engage in a silver(I)-promoted electrocyclic ring-opening/pi-allyl cation cyclization sequence to deliver the hexahydroindole (+/-)-20, which participates in a Suzuki cross-coupling reaction with arylboronic acid 3 to give the tetracyclic compound (+/-)-21. Catalytic hydrogenation of this last compound proceeds in a completely stereoselective manner to give the saturated analogue (+/-)-24, which undergoes Bischler-Napieralski cyclization on reaction with phosphorus oxychloride. The resulting lactam (+/-)-25 is then reduced with lithium aluminum hydride to give (+/-)-gamma-lycorane [(+/-)-1]. By using (-)-menthyl-derived carbamates 27 and 28, this chemistry has been extended to the synthesis of the (+)- and (-)-modifications of the title compound.

Alkaloids↗
PubMed2005

Nature of bonding in the cyclization reactions of (2-Ethynylphenyl)triazene and 2-Ethynylstyrene.

The topological analysis of the electron localization function (ELF) has been applied to explore the nature of bonding in thermal cyclizations of (2-ethynylphenyl)triazene and 2-ethynylstyrene. These processes have been proposed to occur through both five- (i.e., coarctate) and six-membered (i.e., pericyclic) transition states. The analysis of electron delocalization, as measured from an irreducible ELF f-localization domain reduction diagram, allows us to characterize these cyclizations of 2-ethynylstyrene in terms of a more pronounced pericyclic or coarctate character than those associated with (2-ethynylphenyl)triazene. The latter evolve through pseudopericyclic and pseudocoarctate pathways. It is found that ELF results are also in good agreement with recent magnetic evidence data obtained from the anisotropy of induced current density (ACID) calculations.

Journal Article↗
PubMed2005

Growth versus cyclization in the early stages of the polycondensation of metal alkoxides.

The early steps of the polycondensation of transition metal alkoxide have been studied from the chemical and structural points of view. Polyoxoalkoxides are described like macromolecules by the composition of the repeating unit, the degree of polymerization (N), and the radius of gyration (R). The fraction p of binding sites of the coordination sphere of the metal centers occupied by terminal ligands determines N as follows: N proportional, variant pdf (dA-df), where df is the fractal dimension and dA is defined by Np proportional, variant RdA. This approach addresses difficulties raised by both coordinative unsaturation and cyclization in the modelization of the polycondensation of metal alkoxides. The coordinative unsaturation is accounted for by a particularly small value of dA= 1 in the very early steps, while the cyclization frequency is measured by the difference dA-df. This difference is not constant along the polycondensation process, and its dependence on the extent of reaction provides clues for understanding the high apparent kinetics order of gelation often reported in the literature.

Journal Article↗
PubMed2006

Theoretical study of free-radical-mediated 5-exo-trig cyclizations of chiral 3-substituted hepta-1,6-dienes.

Free radical-mediated 5-exo-trig cyclizations of hepta-1,6-dienes incorporating allylsilane, alkyl and alkoxy analogues are modeled using correlated ab initio calculations. The structural, electronic and thermochemical properties of reactants, products and transition species involved in the key step of the radical cyclization process are analyzed and compared with those predicted by the Beckwith-Houk transition models. The product ratios are calculated from the Gibbs energy differences between the possible transition structures following the Curtin-Hammet principle and compared to experimental values.

Journal Article↗
PubMed1999

A cyclized didemnimide alkaloid from the caribbean ascidian didemnumconchyliatum

A novel, cyclized alkaloid of the didemnimide class, 5, has been isolated from extracts of the Caribbean ascidian Didemnum conchyliatum. The structure of 5 was assigned using combined spectral methods that emphasized one- and two-dimensional NMR methods. The new alkaloid is the cyclization product of didemnimide A (1) formed via a C-2 indole condensation with the imidazole nitrogen.

Journal Article↗