Showing papers on "Piperidine published in 1998"
TL;DR: In this paper, a series of new variants of Dde, substituted at the exocyclic alkene position, have been developed and their application in solid phase peptide synthesis assessed.
142 citations
TL;DR: In this article, Salicyaldehyde or its derivatives with various derivatives of ethyl acetate in the presence of piperidine leads to the synthesis of coumarins by a solvent free reaction under microwave irradiation.
Abstract: Condensation of salicyaldehyde or its derivatives with various derivatives of ethyl acetate in the presence of piperidine leads to the synthesis of coumarins by a solvent free reaction under microwave irradiation.
108 citations
TL;DR: The lithium perchlorate-induced ring opening of (S)-triphenylethylene oxide with secondary amines takes place in a stereospecific and completely regioselective manner to afford (R)-2-(dialkylamino)-1,1,2-triphenylthanols (4a-d) to afford aliphatic and aromatic aldehydes 5a-t.
Abstract: The lithium perchlorate-induced ring opening of (S)-triphenylethylene oxide (3) with secondary amines (piperidine (a), N-methylpiperazine (b), N-phenylpiperazine (c) and morpholine (d)) takes place in a stereospecific and completely regioselective manner to afford (R)-2-(dialkylamino)-1,1,2-triphenylethanols (4a-d). These amino alcohols catalytically induce the addition of diethylzinc to benzaldehyde with high enantioselectivity at 0 degrees C and at room temperature. Ligand 4a, which provides the highest enantioselectivity at 0 degrees C, has been studied in the addition of Et(2)Zn to a family of 20 representative aliphatic and aromatic aldehydes 5a-t. For a 17-membered set of alpha-substituted substrates (5a-m,q-t), including ortho-, meta-, and para-substituted benzaldehydes, the naphthaldehydes, alpha,beta-unsaturated and aliphatic (cyclic and acyclic) aldehydes, the mean enantiomeric excess of the resulting alcohols 6a-m,q-t is 97%, whereas for three alpha-unsubstituted specimens (5n-p) the addition takes place with an enantioselectivity of 92-93%.
106 citations
TL;DR: In this paper, Maillard-type reactions from furan-2-carboxaldehyde and primary and secondary amino acids including l-alanine and l-proline have been identified.
Abstract: Colored compounds formed by Maillard-type reactions from furan-2-carboxaldehyde and primary and secondary amino acids including l-alanine and l-proline, respectively, have been identified. When furan-2-carboxaldehyde was heated with l-proline in aqueous solution at pH 7.0, an intensely yellow compound was generated, which was identified as 5(S)-(2-carboxy-1-pyrrolidinyl)-2-hydroxy-(E,E)-2,4-pentadienal-(S)-(2-carboxypyrrolidine)imine (1) by application of several one- and two-dimensional NMR experiments and, in addition, by MS, UV, and IR spectroscopy. Further thermal treatment of compound 1 resulted, upon a ring closure reaction, in the formation of (E)-4,5-bis[(S)-2-carboxy-1-pyrrolidinyl]-2-cyclopenten-1-one (5), which has been, to our knowledge, as yet not reported in the literature. To confirm the proposed structures, l-proline was substituted by pyrrolidine and piperidine, leading to analogous N-cyanines (2 and 3) and cyclopentenones (4 and 6). On the other hand, thermal treatment of an aqueous solu...
75 citations
TL;DR: The kinetic resolutions of both (±)-N-(benzyloxycarbonyl-2-(hydroxymethyl)piperidine [(±)- 5 ] and (±]-N-( tert -butoxy carbonyl)-2-(hexyloxycaronyl) piperidine [6] catalyzed by the enzyme acylase I from Aspergillus species (AA-I) afforded the chiral building blocks (S )- 5 and ( S )- 6, respectively; which were used for the syntheses of the title natural products and
Abstract: The kinetic resolutions of both (±)-N-(benzyloxycarbonyl-2-(hydroxymethyl)piperidine [(±)- 5 ] and (±)-N-( tert -butoxycarbonyl)-2-(hydroxymethyl)piperidine [(±)- 6 ] catalyzed by the enzyme acylase I from Aspergillus species (AA-I) afforded the chiral building blocks ( S )- 5 and ( S )- 6 , respectively; which were used for the syntheses of the title natural products and derivatives of ( S )-pipecolic acid. The syntheses were short (2–4 steps) and proceeded with satisfactory overall yield.
69 citations
TL;DR: The enantioselective syntheses of (S)-coniine and (2R,6R)-trans-solenopsin A are reported and the key step in both syntheses is the catalytic asymmetric hydrosilylation of a cyclic imine.
Abstract: The enantioselective syntheses of (S)-coniine and (2R,6R)-trans-solenopsin A are reported. The key step in both syntheses is the catalytic asymmetric hydrosilylation of a cyclic imine.
64 citations
56 citations
TL;DR: A concise, linear, total synthesis of (--dihydrocodeinone-a close synthetic precursor of (-)-codeine and (-)-morphine-has been achieved and Dimeric byproducts provide evidence for a single electron transfer (SET) mechanism.
Abstract: A concise, linear, total synthesis of (−)-dihydrocodeinonea close synthetic precursor of (−)-codeine and (−)-morphinehas been achieved. The carbocyclic core of the alkaloid was provided in the form of a phenanthrenone, which was resolved by chromatography on cellulose triacetate. A cuprate conjugate addition was used to establish the crucial benzylic quaternary stereocenter and to introduce the C2-side chain. Dimeric byproducts provide evidence for a single electron transfer (SET) mechanism. Unusual SN2 and radical cyclizations were employed for the formation of the dihydrobenzofuran and the piperidine ring, respectively.
48 citations
TL;DR: In this article, an enantioselective (R )-oxynitrilase-catalyzed reaction for the preparation of ( R )-(+)-6-bromo-2-hydroxyhexanenitrile 1 and the subsequent cyclization of this compound to yield the piperidine ring was described.
Abstract: The preparation of ( S )-2-cyanopiperidine 4 provides a new access to 2-substituted piperidines. This synthesis is based on an enantioselective ( R )-oxynitrilase-catalyzed reaction for the preparation of ( R )-(+)-6-bromo-2-hydroxyhexanenitrile 1 and the subsequent cyclization of this compound to yield the piperidine ring. The utilization of 4 as the starting material for the synthesis of ( S )-2-aminomethylpiperidine 6 , ( R )-(−)-coniine 10 and ( S )-(−)-pipecolic acid 13 is also described.
47 citations
TL;DR: In this article, a new strategy was developed for the synthesis of C2-symmetric trans-α,α-α-bis(hydroxymethyl)pyrrolidine and piperidine derivatives 1−3 starting from symmetric α,ω-terminal dienes 4−6.
Abstract: A new strategy has been developed for the synthesis of C2-symmetric trans-α,α‘-bis(hydroxymethyl)pyrrolidine and piperidine derivatives 1−3 starting from symmetric α,ω-terminal dienes 4−6. The doub...
46 citations
TL;DR: In this article, a series of high-affinity NK1 antagonists based on the 4,4-disubstituted piperidine ring system were designed for in vivo study in the resiniferotoxin-induced vascular leakage model.
Abstract: Previously reported studies from these laboratories described the design of a novel series of high-affinity NK1 antagonists based on the 4,4-disubstituted piperidine ring system. Further structure−activity studies have now established that for high NK1 affinity the benzyl ether side chain must be 3,5-disubstituted and highly lipophilic, the optimal side chain being the 3,5-bis(trifluoromethyl)benzyl ether, 12 (hNK1 IC50 = 0.95 nM). Additional studies have shown that this class of NK1 antagonist tolerates a wider range of substituents on the piperidine nitrogen, including acyl (38) (hNK1 IC50 = 5.3 nM) and sulfonyl (39) (hNK1 IC50 = 5.7 nM) derivatives. Following preliminary pharmacokinetic analysis, two compounds (32 and 43) were selected for in vivo study in the resiniferotoxin-induced vascular leakage model, both showing excellent profiles (ID50 = 0.22 and 0.28 mg/kg, respectively).
TL;DR: Various N-pent-4-enylglycine methyl esters have been submitted to carbocyclization of their zinc enolates onto the unactivated double bond, finding a way to di-, tri-, tetra-, or pentasubstituted piperidines.
Abstract: Various N-pent-4-enylglycine methyl esters have been submitted to carbocyclization of their zinc enolates onto the unactivated double bond. The cyclization to substituted pipecolic esters is highly stereoselective. In most cases, substitution of the pent-4-enyl moiety on various sites leads to a single isomer, hence a way to di-, tri-, tetra-, or pentasubstituted piperidines.
TL;DR: In this article, the synthesis of Elaeocarpus alkaloid (−)-Elaeokanine C in the naturally occurring form was achieved using nickel-catalyzed cyclization of 1,3-diene and aldehyde in a chain.
Patent•
15 Apr 1998TL;DR: A hair dye composition for dyeing keratinic fibres, especially human hair, contains: (a) one or more keto-and/or aldehyde compounds which colour human hair either alone or in the presence of a compound of type (B); (b) at least one compound with primary or secondary amino groups or hydroxy groups selected from primary and secondary aliphatic or aromatic amines, N-containing heterocyclic compounds, aminoacids, oligopeptides made up of 2-9 amino acids and aromatic hydroxy compounds, and
Abstract: A hair dye composition(s) for dyeing keratinic fibres, especially human hair, contains: (A) one or more keto- and/or aldehyde compounds which colour keratinic fibres either alone or in the presence of a compound of type (B); (B) at least one compound with primary or secondary amino groups or hydroxy groups selected from primary and secondary aliphatic or aromatic amines, N-containing heterocyclic compounds, aminoacids, oligopeptides made up of 2-9 aminoacids and aromatic hydroxy compounds, and/or at least one CH-active compound; and (C) a colour strengthening agent (booster) selected from piperidine, pyridine, imidazole, pyrrolidine, pyrrolidone, pyrazole, triazole, piperazidine, derivatives of these and their salts; provided that (B) and (C) are different.
TL;DR: In this article, a method for polymer-supported synthesis of piperazine and piperidine libraries on the basis of nucleophilic aryl substitution (S n Ar) and N-acylation is reported.
TL;DR: The gold(I) complexes (pip)2Au+Cl- and (Cy2NH)AuCl (Pip=piperidine, Cy=cyclohexyl) crystallise as loose dimers; in the ionic species N-H···Cl- hydrogen bonding is the main secondary interaction, whereas in the neutral complex the N−H·Cl hydrogen binding is weaker but is compensated by an auriophilic interaction as discussed by the authors.
Abstract: The gold(I) complexes (pip)2Au+Cl- and (Cy2NH)AuCl (pip=piperidine, Cy=cyclohexyl) crystallise as loose dimers; in the ionic species N–H···Cl- hydrogen bonding is the main secondary interaction, whereas in the neutral complex the N–H···Cl hydrogen bonding is weaker but is compensated by an auriophilic interaction.
TL;DR: In this paper, the spectral properties of 1,8-naphthoic anhydride and 1,2,6,6-tetramethyl-4-hydroxypiperidine in methanol and non-polar cyclohexane were investigated.
Abstract: Fluorescence probes of type N -(1′- R -2′,2′,6′,6′-tetramethyl-4′-piperidinyl)-1,8-naphthaleneimide exhibit spectral properties which are influenced by environment and substitution ( R ) on sterically hindered nitrogen of piperidine moiety. Absorption spectra of parent amine and its N substituted derivatives show the longest wavelength band around 340 nm (log ɛ ∼ 4.0) which is well resolved in cyclohexane. In polar methanol it is only slightly blue shifted. Substitution on sterically hindered nitrogen does not influence the absorption spectra in near UV region. Fluorescence spectra of the probes have maximum around 385 nm in methanol and comparable intensity as anthracene. In nonpolar cyclohexane the fluorescence intensity is low (more than 100×). In nonpolar isotactic polypropylene matrix the red shifted excimer like emission in the range 440–470 nm was observed. The N -oxy and N -hydroxy derivatives under the same conditions do not yield the excimer emission. In other polymer matrices as polystyrene, poly(methyl methacrylate) and polyvinylchloride similar emission as in methanol was observed, the emission in latter matrix being the most intense. The fluorescence lifetime in polar solvent and matrices is less then 1 ns and deviates slightly from monoexponential. In nonpolar iPP, the fluorescence lives longer around 5 ns and its decay is more complex. Intermolecular quenching of the probes by 1-oxy-2,2,6,6-tetramethyl-4-hydroxypiperidine in methanol occurs at the rate which is above the diffusion controlled limit what might indicate the involvement of the polar medium in the process. Intramolecular quenching, expressed as the ratio I NH / I NO for parent and oxidized amine respectively, strongly depends on the medium as well. In polar methanol this ratio is about 30 while in polymer matrices 2–4 only. Photolysis of probes doped in polymer matrices with radiation above 300 nm revealed that the parent amine is about 3× more stable as 1,8-naphthoic anhydride or N -octadecyl-1,8-naphthaleneimide.
TL;DR: In this paper, two AD reactions in a stepwise manner lead to the anti-1,5-diol and syn 1,5diol stereodivergently, which have been converted by aminocyclization into trans and cis -2,6-disubstituted piperidines (trans - and cis-12 ), respectively.
TL;DR: The easier dissociation of the amine ligand explains why monodentate amines give good yields of the corresponding enamines in contrast to bidentates amines.
TL;DR: An efficient methodology for a solid phase synthesis of D- and L-cycloserine derivatives is described, which results in immobilized cycloserine reagents with a primary amino group exposed for various synthetic transformations.
TL;DR: Enantiomerically pure 3-amino cyclic amines such as pyrrolidine, piperidine, and 2,3,4,5,6,7,hexahydro-1H-azepine have been synthesized in high yields from the optically active natu....
TL;DR: The enantiomerically pure 11c–g and 12c-g (ee > 99 %), 1-aryl-tetrahydroisoquinolines, were evaluated for their affinity to the PCP [1-(1-phenylcyclohexyl)piperidine] binding site of the NMDA (N-methyl D-aspartate) receptor and in each case the enantiomers 11 exhibited a higher affinity than those of 12.
TL;DR: In this article, the enantioselective synthesis of acid (+)-(2) was extended to enanti-selective synthesis for the glandular secretion from the civet cat (Viverra civetta).
Abstract: The oxyanion derived from hydroxyacrylate E-(5) undergoes smooth intramolecular Michael addition to give the trans-2,6-disubstituted tetrahydropyran (7) as the major product of reaction. In contrast, the oxyanion obtained from isomer Z-(5) cyclizes to give the cis-2,6-disubstituted tetrahydropyran (6) as the major product. Such chemistry has been extended to the enantioselective synthesis of (+)-(6) the acquisition of which constitutes a formal total synthesis of acid (+)-(2), a constituent of the glandular secretion from the civet cat (Viverra civetta). Reductive amination of keto acrylate (12) affords an intermediate amine which cyclizes, in situ, to give the cis-2,6-disubstituted piperidine (26). Analogous treatment of compound (13) delivers the isomeric trans-2,6-disubstituted piperidine (27) as the exclusive product of reaction. Transition state structures have been proposed to account for the diastereoselectivities observed in all of the cyclization reactions.
TL;DR: The inhibition of radioligand binding and [35S]GTPgammaS functional assay data for N- methyl- and N-phenethyl-9beta-methyl-5-(3-hydroxyphenyl)morphans (5b and 5c) show that these compounds are pure antagonists at the micro, delta, and kappa opioid receptors, and suggest that the trans-3, 4-dimethyl-4-dimethyltestosterone-4-(3
Abstract: The inhibition of radioligand binding and [35S]GTPgammaS functional assay data for N-methyl- and N-phenethyl-9beta-methyl-5-(3-hydroxyphenyl)morphans (5b and 5c) show that these compounds are pure antagonists at the micro, delta, and kappa opioid receptors. Since 5b and 5c have the 5-(3-hydroxyphenyl) group locked in a conformation comparable to an equatorial group of a piperidine chair conformation, this information provides very strong evidence that opioid antagonists can interact with opioid receptors in this conformation. In addition, it suggests that the trans-3, 4-dimethyl-4-(3-hydroxyphenyl)piperidine class of antagonist operates via a phenyl equatorial piperidine chair conformation. Importantly, the close relationship between the 4-(3-hydroxyphenyl)piperidines and 5-(3-hydroxyphenyl)morphan antagonists shows that the latter class of compound provides a rigid platform on which to build a novel series of opioid antagonists.
TL;DR: YM-35375 may be a new lead compound for novel NK2 receptor antagonists or NK1-NK2 dual antagonists and energy calculation of a variety of substituted 4-phenyl piperidines revealed that spiro[isobenzofuran-1(3H),4'-piperidine] possesses a conformationally restricted equatorial phenyl group.
Abstract: Analysis of the structural requirements of compound 1 (SR48968), a potent NK2 receptor antagonist, revealed that the 4-phenyl group of the piperidine is essential for binding with the NK2 receptor and occupies an equatorial position. Energy calculation of a variety of substituted 4-phenyl piperidines revealed that spiro[isobenzofuran-1(3H), 4'-piperidine] possesses a conformationally restricted equatorial phenyl group. Our compound 12 (YM-35375) possessing this spiro-substituted piperidine bound to the NK2 receptor with an IC50 value of 84nM and to NK1 receptor with an IC50 value of 710nM. It showed more potent inhibitory activity (ID50 41μg/kg (i.v.)) against [β-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than (±)-SR48968 (ID50 68μg/kg (i.v.)). YM-35375 may be a new lead compound for novel NK2 receptor antagonists or NK1-NK2 dual antagonists.
TL;DR: The highly regioselective cyclohydrocarbonylation of 4-amido-1,6-heptadienes catalyzed by Rh-BIPHEPHOS complex gives functionalized piperidines quantitatively, which serve as versatile intermediates for the syntheses of a variety of piperidine and quinolizidine alkaloids.
TL;DR: In this paper, a short and efficient chiral synthesis of 6-aryl-5-phenylsulfonyl-1,2,5,6-tetrahydropyridines was achieved in moderate yield and with good selectivity.
Abstract: A short and efficient chiral synthesis of 6-aryl-5-phenylsulfonyl-1,2,5,6-tetrahydropyridines was achieved in moderate yield and with good selectivity. The absolute configurations were assigned by extending the methodology to ( S )-anatabine and as well with NMR experiments.
TL;DR: One-pot oxidation polymerization of dithiols, obtained from bifunctional cyclic dithiocarbonates (4a and 4b) with two equivalents of amines, was studied in this article.
Abstract: One-pot oxidation polymerization of dithiols, obtained from bifunctional five-membered cyclic dithiocarbonates (4a and 4b) with two equivalents of amines, was studied. The monomers 4a and 4b were synthesized by the reactions of bisphenol A diglycidyl ether and neopentyl glycol diglycidyl ether with carbon disulfide, respectively. Polydisulfides with M n s 4600-20,200 were obtained quantitatively in the oxidation polymerization of the dithiols obtained in situ by the reactions of 4a with benzylamine, n -butylamine, and piperidine. On the other hand, dithiols obtained from 4b with benzylamine, afforded cyclic disulfides as well as the polydisulfide under similar conditions.