Showing papers on "Piperidine published in 1997"

Synthesis and Biological Evaluation of Aza-C-disaccharides: (1→6), (1→4), and (1→1) Linked Sugar Mimics

Abstract: The synthesis of (1→6), (1→4), and (1→1) linked aza-C-disaccharides, a novel class of glycomimetic compounds, is described. The polyhydroxylated piperidine ring was synthesized using vinyl bromide 11 as a common intermediate which was synthesized de novo from bromobenzene utilizing the microbial oxidation metabolite bromodiol 10. A Suzuki coupling of 11 with an alkylboron reagent derived from olefinated carbohydrate precursors via hydroboration was used to form the C-glycosidic bond. Ozonolysis and selective reduction of the resultant carbonyl functions served to produce the azasugar ring. Fully deprotected aza-C-disaccharides were obtained upon acidic deprotection. Biological screening of the title compounds against several common glycosidase enzymes as well as in vitro anti-HIV assays are reported.

A General Synthetic Entry to Strychnos Alkaloids of the Curan Type via a Common 3a-(2-Nitrophenyl)hexahydroindol-4-one Intermediate. Total Syntheses of (±)- and (−)-Tubifolidine, (±)-Akuammicine, (±)-19,20-Dihydroakuammicine, (±)-Norfluorocurarine, (±)-Echitamidine, and (±)-20-Epilochneridine1

Abstract: A general strategy for the synthesis of pentacyclic Strychnos alkaloids with the curan skeleton has been developed. It utilizes 3a-(2-nitrophenyl)hexahydroindol-4-one (23), which was prepared from 2-allyl-2-(2-nitrophenyl)-1,3-cyclohexanedione (15), as the common, pivotal intermediate. Three different procedures have been employed for the closure of the bridged piperidine D ring from 23: (i) an intramolecular Michael-type conjugate addition; (ii) a Ni(COD)2-promoted biscyclization that assembles B and D rings in a single synthetic step, and (iii) an intramolecular cyclization of an enone−propargylic silane system. When necessary, depending on the procedure used, introduction of the oxidized one-carbon substituent at C-16, closure of the indole ring, and/or adjustment of the functionality of the C-20 two-carbon chain constitute the last stages of the synthetic route to the title alkaloids. The procedure involving the cyclization of a propargylic silane has been successfully extended to the enantiospecific...

Amine functions linked to MCM-41-type silicas as a new class of solid base catalysts for condensation reactions

Abstract: MCM-41 type silica surfaces were grafted with primary amino groups through silanation process. Tertiary amino groups covalently bound to the surface were prepared through displacement of previously anchored halogen atom by piperidine. The catalytic activities of the immobilized amino groups were studied in the Knoevenagel condensation of benzaldehyde with ethylcyanoacetate. The mechanism of the catalyst action is discussed

Synthesis of selenocysteine peptides and their oxidation to diselenide-bridged compounds.

Abstract: Using the Fmoc/tBu protection scheme and the p-methoxybenzyl derivative of selenocysteine, the synthesis of related peptides in the selenol-protected form could be optimized by operating the coupling steps in the absence of auxiliary bases and by reducing the piperidine treatment to the minimum time required for quantitative Fmoc cleavage. Under these conditions, β-elimination of the p-methoxybenzylselenol as the main side reaction of these syntheses, as well as epimerization of the protected selenocysteine, was largely suppressed. Conversion of the selenol- and thiol-protected bis-selenocysteine and selenocysteine, cysteine peptides into the related cyclic monomeric forms by iodine-mediated oxidation failed since a complex mixture of compounds was produced. Cleavage of the selenoether bond with mercuric acetate was found to proceed smoothly, but displacement of the heavy metal ions by treatment with excesses of thiols or hydrogen sulphide was unsuccessful since a stable Hg2+ diselenide complex was obtained. However, oxidation was achieved in good yields by the dimethylsulphoxide/trifluoroacetic acid procedure and the peptides were then used for determining the redox potential of the diselenide and selenide/sulphide bridge, respectively. © 1997 European Peptide Society and John Wiley & Sons, Ltd.

Piperidine derivatives, pharmaceutical compositions thereof and their use in the treatment of hepatitis c

Abstract: Derivatives of piperidine are useful in prophylaxis and treatment of hepatitis C virus infections.

Applications of Organosulfur Chemistry to Organic Synthesis: Total Synthesis of (+)-Himbeline and (+)-Himbacine

Abstract: Total syntheses of (+)-himbacine (1) and (+)-himbeline (2) are described. The synthesis involves the preparation of sulfone 38 and aldehyde 42 as single enantiomers followed by coupling of these compounds using a Julia−Lythgoe olefination. The preparation of sulfone 38 features an acid-promoted intramolecular Diels−Alder reaction of an α,β-unsaturated thioester while the synthesis of 42 features a Beak alkylation of piperidine 39.

Novel Heterospirocyclic 3-Amino-2H-azirines as Synthons for Heterocyclic α-Amino Acids†‡

Abstract: The heterospirocyclic N-methyl-N-phenyl-2H-azirin-3-amines (3-(N-methyl-N-phenylamino)-2H-azirines) 1a-d with a tetrahydro-2H-pyran, tetrahydro-2H-thiopyran, and a N-protected piperidine ring, respectively, were synthesized from the corresponding heterocyclic 4-carboxamides 2 by consecutive treatment with lithium diisopropylamide (LDA), diphenyl phosphorochloridate (DPPCl), and sodium azide (Scheme 4 ). The reaction of these aminoazirines with thiobenzoic acid in CH2Cl2 at room temperature gave the thiocarbamoyl-substituted benzamides 13a - d in high yield. The azirines l a - d were used as synthons for heterocyclic 1-amino acids in the preparation of tripeptides of the type Z-Aib-Xaa-Aib-N(Ph)Me (18) by following the protocol of the „azirine/oxazolone method“: treatment of Z-Aib with 1 to give the dipeptide amide 15, followed by selective hydrolysis to the corresponding acid 16 and coupling with the 2,2-dimethyl-2H-azirin-3-amine 17 gave 18, again in high yield (Scheme 5 ). With some selected examples of 18, the selective deprotection of the amino and the carboxy group, respectively, was demonstrated (Scheme 6). The solid-state conformations of the protected tripeptides 18a - d, as well as that of the corresponding carbocyclic analogue 18e, were determined by X-ray crystallography (Figs. 1 - 3 and Tables 1 - 3). All five tripeptides adopt a beta-turn conformation of type III or III’. The solvent dependence of the chemical shifts of the NH resonances (Fig. 6) suggests that there is an intramolecular H-bond between H-N(4) and O(11) in all cases, which is an indication that a relatively rigid beta-turn structure also persists in solution. Surprisingly, the tripeptide acid 20a shows no intramolecular H-bond in the crystalline state (Fig. 7); O(11) is involved in an intermolecular H-bond with the OH group of the carboxy function.

A Route to exo-Heterodisubstituted and Monosubstituted o-Carborane Derivatives.

Abstract: A method leading to the synthesis of monothioethers and heterodisubstituted o-carborane derivatives containing Cc−PPh2 and Cc−SR groups is described. Their partial degradation preserving the two functional groups was achieved with piperidine in ethanol. The molecular structure of a closo compound is indicated in the figure.

Novel piperidine containing compounds

Abstract: Novel-3-carboxyindole piperidine amide containing compounds, and compositions for use in therapy as anti-inflammatory agents, and inhibitors cytokine p38/MAP kinase mediated diseases.

Complex Catalysis, XLIX On the Coordination of Olefins and Secondary Amines at the Cationic [2,6‐Bis(diphenylphosphanylmethyl)pyridine]rhodium(I) Fragment [Rh(PNP)]+ ‐ Synthesis and Characterization of [Rh(PNP)(L)]X (L = Ethylene, Styrene, HNR2; X = BF4, PF6, CF3SO3)

Abstract: The cationic rhodium(1) complexes [Rh(PNP)(C2H4)]X; X = BF4 (1a), PF6 (1b), CF3SO3 (1c ) were prepared by addition of the tridentate ligand 2,6-bis(diphenylphosphanylmethyl)pyridine (PNP) to a solution of [Rh(C2H4)2(solv)2]X (solv = acetone or THF) under ethylene. The complexes were characterized by IR and 1H-, 13C-, and 31P-NMR spectroscopy. The coordination of two ethylene molecules at the [Rh(PNP)]+ fragment could be detected by dynamic proton resonance of a solution of 1a under free ethylene. The styrene complex [Rh(PNP)(styrene)]BF4 (4) was obtained by substitution of the ethylene from 1a with an excess of styrene. The π coordination of C2H4 and styrene in 1a and 4 respectively was confirmed by X-ray crystal structure analysis. The olefin complexes react with an excess of the secondary amine to give the corresponding amine complexes [Rh(PNP)(HNR2)]X; HNR2 = piperidine (5), HNMe2 (6 ), HNEt2 (7). Conversly, the amine could be released from the amine complexes with an excess of ethylene at low temperature by the formation of the ethylene complex 1.

Structure−Reactivity Correlations in the Aminolysis and Pyridinolysis of Bis(phenyl) and Bis(4-nitrophenyl) Thionocarbonates

Abstract: The reactions of a series of secondary alicyclic amines with bis(phenyl) and bis(4-nitrophenyl) thionocarbonates (BPTOC and BNPTOC, respectively), and a series of pyridines with the latter substrate, are subjected to a kinetic investigation in water, 25.0 °C, ionic strength 0.2 M (KCl). All the reactions obey pseudo-first-order kinetics under amine excess over the substrate. The reactions of piperidine with BPTOC are first order in amine, but those of the same substrate with the other secondary alicyclic amines exhibit a complex order, consistent with the existence of both a zwitterionic (T±) and an anionic (T-) tetrahedral intermediates on the reaction pathway. Deprotonation of T± by a secondary amine to give T- (rate coefficient k3) competes with expulsion of the amine moiety from T± (k-1), except in the reactions of 1-formylpiperazine whereby k-1 ≫ k3 [1-formylpiperazine], and a kinetics second order in amine is observed. The reactions of secondary alicyclic amines with BNPTOC are all first order in am...

EFFICIENT SYNTHESIS OF α-ENAMINOPHOSPHONATES IN THE SERIES OF PIPERIDINE AND MORPHOLINE. Examples of synthetic applications

Abstract: Various α-piperidino or a-morpholino alkenylphosphonates are conveniently prepared from the related α-hetero-substituted methylphosphonates, through a Peterson olefination process, which can be easily adapted for a direct homologation of aldehydes into carboxylic acids. An efficient synthesis of α-piperidino or α-morpholino alkylphosphonates and phosphonic acids is proposed.

Nitrosation of Amines in Nonaqueous Solvents. 2. Solvent-Induced Mechanistic Changes

Abstract: We studied the nitrosation of amines (pyrrolidine, piperidine, diethylamine, N-methylpiperazine, N,N′-dimethylethylenediamine, and morpholine) by alkyl nitrites (2-bromoethyl nitrite or 2,2- dichloroethyl nitrite) or by N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in the solvents chloroform, acetonitrile, and dimethyl sulfoxide (DMSO). The mechanism of nitrosation by alkyl nitrites depends on the solvent: in chloroform, all the results were in keeping with formation of a hydrogen-bonded complex between the amine and alkyl nitrite being followed by rate-controlling formation of a tetrahedral intermediate T± that rapidly decomposes to afford the final products; in acetonitrile, a situation intermediate between those obtaining in chloroform and cyclohexane results in the [amine] dependence of the first-order pseudoconstant k0 being qualitatively influenced by temperature and by the identities of both the amine and the alkyl nitrite; in DMSO, the results suggest a mechanism close to the mechanism acting in water. For nitrosation by MNTS, k0 depended linearly on [amine] in all three solvents. The Grunwald-Winstein coefficients correlating the rate constants k for nitrosation by MNTS in the chloroform, acetonitrile, DMSO, dioxane, dichloromethane, and water were l = 0.12 and m = 0.29. Correlation with the Kamlet-Abboud-Taft equation confirmed that k depends largely on the dipolarity of the solvent and, to a lesser extent, its capacity for hydrogen bonding.

4-hydroxy-piperidine derivatives

Abstract: The present invention relates to compounds of the general formula (see formula I) wherein X is -O-, -NH-, -CH2-, -CH=, -CO2-, -CONH-, -CON(lower alkyl)-, -S- and -SO2-; R1 - R4 are, independently from each other hydrogen, halogen, hydroxy, amino, nitro, lower-alkyl-sulfonylamido, 1- or 2-imidazolyl, 1-(1,2,4-triazolyl) or acetamido; R5, R6 are, independently from each other hydrogen, lower alkyl, hydroxy, lower alkoxy or oxo; R7-R10 are, independently from each other hydrogen, lower- alkyl, halogen, trifluoromethyl or lower-alkoxy; n is 0 or 1; and to pharmaceutically acceptable acid addition salts thereof. Compounds of the present invention are NMDA(N-methyl-D-aspartate)- receptor subtype selective blockers.

Mixed-ligand complexes of cobalt(iii) with dithiocarbamates and a cyclic tetradentate secondary amine

Abstract: 4-Morpholine-, piperidine-, 4-piperazine- and N-methyl- piperazine-dithiocarbamate complexes of Cobalt (III) with 1, 4, 8, 11-tetraazacyclotetradecane, of general formula [Co(Rdtc)cyclam] (C104)2, have been prepared and have been characterized. The complexes adopt cis-octahedral geometry with folded macrocyclic ligand and with the dithiocarbamate bound as a bidentate. trans-influence of the dithiocarbamate ligands was studied by NMR spectroscopy and established the order piperidine-dtc > 4-morpholine-dtc > N-methyl-piperazine-dtc.

Use of derivatives of tetrahydro-beta-carbolines as antimetastatic agents

Abstract: The present invention concerns the use of beta-carboline derivatives of formula (I) bearing at least a free or esterified carboxylic group on the piperidine ring, for the preparation of pharmaceutical compositions having antimetastatic properties.

Asymmetric total syntheses of hydroxylated piperidine alkaloids via the intramolecular reaction of γ-aminoallylstannane with aldehyde

Abstract: Asymmetric total syntheses of (+)-desoxoprosopinine and (−)-desoxoprosophylline were accomplished using L-glutamic acid as the chiral source, in which the intramolecular reaction of a γ-aminoallylstannane with an aldehyde was used as a key step.

Synthesis of new organic phosphites containing sterically hindered piperidine groups

Abstract: The synthesis of several phosphites with sterically hindered piperidine groups which are potential stabilizers for synthetic polymers is described. The reaction of phosphorous acid hexaethyltriamide (1) with the 4-hydroxypiperidine compounds 2 and 3 in a 1:1 and 1:2 ratio gives the phosphorous acid monoester diamides 4 and 5 and phosphorous acid diester monoamides 6 and 7, respectively. These compounds can be selectively hydrolyzed to the phosphorous acid diesters 8 and 9 and to the phosphorous acid monoesters 14 and 15. The new phosphorous acid ester amides 4, 5, 6 and 7 are useful building blocks for the synthesis of phosphites with sterically hindered piperidine moieties. Several representatives of this class of compounds are described.