Showing papers on "Piperidine published in 1993"
TL;DR: In this paper, an efficient asymmetric aza-Diels-Alder reaction using chiral boron mediator is developed using α-benzylamine as a chiral auxiliary.
131 citations
TL;DR: The use of 1 equiv of Vilsmeier reagent under mild conditions (CICHCCl 2, rt) transformed several racemic Nacyl-2,3-dihydro-4-pyridones 3 to dihydropyridines 4 in very good to excellent yields (83-96%) as mentioned in this paper.
Abstract: The full details are given of a study on the conversion of dihydropyridones of the type 3 to 4-chloro-1,2-dihydropyridines 4 using a Vilsmeier reagent. The use of 1 equiv of Vilsmeier reagent under mild conditions (CICHCCl 2 , rt) transformed several racemic N-acyl-2,3-dihydro-4-pyridones 3 to dihydropyridines 4 in very good to excellent yields (83-96%). A C-3 methyl group can be tolerated as was demonstrated in the preparation of 4-chloro-3-methyl-1,2-dihydropyridine 7 from dihydropyridone 6 in 90% yield. The utility of this conversion was demonstrated in the synthesis of the piperidine alkaloid, (-)-coniine. The synthesis of (-)-coniine was completed in five steps from 4-methoxy-3(triisopropylsilyl)pyridine in 54% overall yield. When 2,3-dihydro-4-pyridones are treated with excess Vilsmeier reagent, good yields of 4-chloro-3-formyl-1,2-dihydropyridines result. These heterocycles are useful intermediates for alkaloid preparation, as shown by two syntheses of the quinolizidines alkaloid, (±)-lupinine, carried out in three and five steps, respectively
63 citations
TL;DR: In this paper, a model study for the syntheses of dendrobatid alkaloids has been conducted, and high regio-and stereoselective approaches for synthesizing dendrobids have been developed.
Abstract: Remarkably high regio- and stereoselective approaches for the syntheses of dendrobatid alkaloids (+)-allopumiliotoxin 267A and 339A have been developed. As a model study for the syntheses of these alkaloids, we initially undertook intramolecular chromium(II)-mediated cyclization of the racemic N-(iodoalkenyl)piperidine 8, which smoothly proceeded by treatment with CrCl 2 (5 equiv) and catalytic NiCl 2 (2.5 mol%) in DMF to form a 1.3:1 epimeric mixture of 2-hydroxy-3(E)-alkylidene-trans-quinolizidines 33a and 33b. When the alternative chiral N-(iodoalkenyl)piperidine 9 was subjected to the identical cyclization conditions, the 3(E)-alkylidene-trans-quinolizidine 35a with the axially oriented 2-hydroxy group was formed as a single isomer. Based on these model studies, we then undertook the enantioselectivie total synthesis of (+)-allopumiliotoxin 267A (1). For the synthesis of (1), coupling of the two segments, (E)-vinyl iodide 45, obtained via stereospecific palladium-catalyzed hydrostannation, and the pyrrolidine derivative 54, gave the N-(iodoalkenyl)pyrrolidine 56, which underwent intramolecular chromium-(II)-mediated cyclization, exclusively providing 58 with complete retention of the required (E)-alkenyl geometry. Subsequent cleavage of the benzyl group furnished 1. Synthesis of allopumiliotoxin 339A (2) was next investigated bu employing the strategy developed for 1. The side-chain segment, (E)-vinyl iodide 74, was prepared via high-degree stereo- and regioselective reactions involving Evans alkylation and palladium-catalyzed hydrostannation. Intramolecular nickel (II)/chromium(II)-mediated cyclization of the N-(iodoalkenyl)pyrrolidine 82, available via coupling 74 with pyrrolidine derivative 79, led to exclusive formation of 83, which was deprotected to afford 2
57 citations
TL;DR: In this paper, the authors investigated the effect of the Fmoc group on the secondary structure of the peptide H-(Ala) 6 -Lys-OH on a polyacrylamide gel resin, followed by near-infrared Fourier transform (FT) Raman spectroscopy.
Abstract: The stepwise solid-phase synthesis of the peptide H-(Ala) 6 -Lys-OH on a polyacrylamide gel resin was followed by near-infrared (NIR) Fourier-transform (FT) Raman spectroscopy. In particular, this investigation involved the use of Fmoc as the N-α-protecting group. The deprotection of the Fmoc group by standard methods could be quantitatively followed. The deprotection was essentially complete until a number of alanine residues in multiples of six were reached, with nearly one-third of the peptide chains left protected after the standard piperidine treatment. Even a prolonged deprotection time did not result in a complete deprotection of the Fmoc group. This phenomenon could be attributed to the formation of secondary structures, which were indicated by structurally sensitive Raman bands, with particular focus on the amide III bands. The Fmoc group was found to have a clear influence upon the secondary structure, supporting mainly a β-sheet conformation, whereas more coiled forms were found for the deprotected samples. Preliminary studies with the use of Boc as the N-α-protecting group showed that this group had essentially no importance for the secondary structure of the pendent peptide chains. Investigation of peptides containing both D- and L-chiral forms of alanine supported the hypothesis that the presence of the Fmoc group influences the secondary structure. The swelled forms of the sequence Fmoc-(Ala) 6 -Lys(Boc)-OR in DMSO or DMF showed different secondary structures, indicating different interactions between the peptide chains and the two solvents. Our studies show that Raman spectroscopy is a nondestructive analytical tool which allows a recording of spectra while the peptide is directly bound to the solid support under normal synthetic conditions
56 citations
TL;DR: In this paper, three piperidine alkaloids were isolated and identified from the leaves of Pandanus amaryllifolius using 2D NMR techniques including inverse-detected Heteronuclear multiple Bond Correlation (HMBC) and HMQC spectroscopy.
53 citations
TL;DR: In this paper, seven new unsaturated amides, together with six known ones, were isolated, and their structures were determined to be N-isobutyl-2E,4E,12Z-octadecatrienamide (1), Nisobubyl 2E, 4E, 14Z-eicosatrienamide(2), 1-(eicosa-2Es2E-4E-14Z-trienoyl)piperidine (3), 1.
Abstract: Amides in a CH2Cl2 extract from the fruits of Piper retrofractum were detected by HPLC/APCI-MS. Seven new unsaturated amides, together with six known ones, were isolated, and their structures were determined to be N-isobutyl-2E,4E,12Z-octadecatrienamide (1), N-isobutyl-2E,4E,14Z-eicosatrienamide (2), 1-(octadeca-2E,4E,12Z-trienoyl)piperidine (3), 1-(eicosa-2E,4E,14Z-trienoyl)piperidine (4), 1-(octadeca-2E,4E-dienoyl)piperidine (5), 1-(eicosa-2E,4E-dienoyl)piperidine (6), and 1-(eicosa-2E,14Z-dienoyl)piperidine (7) on the basis of chemical and spectroscopic evidence.
38 citations
TL;DR: Epimeric oxazolopiperidones represent chiral potential iminium ions in R-(-)-phenylglycinol as starting material.
Abstract: Epimeric oxazolopiperidones (1a) and (1b) were prepared independently, both from R-(-)-phenylglycinol as starting material. They represent chiral potential iminium ions
37 citations
Patent•
11 Feb 1993
TL;DR: The present invention relates to a group of piperazine and piperidine derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their use in therapy, in particular in the treatment of psychotic disorders as discussed by the authors.
Abstract: The present invention relates to a group of piperazine and piperidine derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their use in therapy, in particular in the treatment of psychotic disorders.
36 citations
TL;DR: Con conformational analyses have been performed on cocaine, the potent analog 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane (CFT, 2), and a group of dopamine reuptake blockers that contain two phenyl rings, finding the N‐methyl groups in 1 and 2 are found to strongly prefer the equatorial position of the piperidine ring.
Abstract: Using the MM2-87 program and parameter set, conformational analyses have been performed on cocaine (1), the potent analog 2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT, 2), and a group of dopamine reuptake blockers that contain two phenyl rings. The latter includes LU 19-005 (3), a 1-amino-4-phenyltetralin (4), a hexahydropyrrolo[2,1-a]isoquinoline (5), diclofensine (6), and a hexahydro[1,2-b]pyridine (7). Using different values for the dielectric constant, the global minimum of 1 and 2 is a conformer in which there is a favorable electrostatic interaction between the ammonium hydrogen and the carbonyl of the carbomethoxy group. The N-methyl groups in 1 and 2 are found to strongly prefer the equatorial position of the piperidine ring. These results were also related to four crystal structures of 1 and its close derivatives. Compounds 3–7 are found to have a common conformation that was used to define the pharmacophore for dopamine reuptake blockers including the required orientation of the ammonium hydrogen. The pharmacophore provides an explanation for why the tertiary amine analogs of 3 and 4 are less potent than the secondary amines because the added N-methyl group occupies the position required for the ammonium hydrogen. This explanation, however, does not work for 7, in which the tertiary amine is again less active than the secondary amine. However, this last series appears to have a number of anomalous features. Superposition of 2 with the pharmacophore suggests that its carbomethoxy may occupy the same region of the receptor as the second phenyl ring in compounds 3–7. © 1993 John Wiley & Sons, Inc.
33 citations
TL;DR: The dissociation constants of piperidine, 1-piperidineethanol, N-methylmorpholine, 4-(2-hydroxyethyl)morpholine (4-EML), and tropine have been determined at 15.0, 25.0 and 35.0 as discussed by the authors.
Abstract: The dissociation constants of piperidine (PD), 1-piperidineethanol (1–PE), N-methylmorpholine (MML), 4-(2-hydroxyethyl)morpholine (4-EML), and tropine (TP) have been determined at 15.0, 25.0, 35.0,...
33 citations
TL;DR: The first tetracyclic ABDE ring systems were obtained by a straightforward sequence consisting of nucleophilic addition of a 1-indoleacetic ester enolate to the γ position of a pyridinium salt, acid cyclization of the resulting 1,4-dihydropyridine, and final elaboration of the (E)-ethylidene substituent as discussed by the authors.
Abstract: Closure of the six-membered C ring of pentacyclic mavacurine-type alkaloids from suitably substituted tetracyclic substructures embodying rings ABDE of these alkaloids, either by electrophilic cyclization upon the indole 3-position or by intramolecular alkylation of the piperidine nitrogen, failed. In contrast, 6a-homopleiocarpamine (45) has been synthesized from dithioacetal 42 by an electrophilic cyclization involving the closure of the seven-membered C ring. The first total synthesis of the alkaloid 2,7-dihydropleiocarpamine (58) has been achieved by photocyclization of the tetracyclic chloroacetamide 54 as the key step. The required tetracyclic ABDE ring systems were prepared by a straightforward sequence consisting of nucleophilic addition of a 1-indoleacetic ester enolate to the γ position of a pyridinium salt, acid cyclization of the resulting 1,4-dihydropyridine, and final elaboration of the (E)-ethylidene substituent. An alternative synthesis of the tetracyclic alkaloid vinoxine (10a) is also reported
TL;DR: Two 4-alkylidene compounds and a 4,4-cyclic dialkyl compound showed potent activity when administered either intravenously or perorally.
Abstract: Some (piperidinomethylene)bis(phosphonic acid) derivatives were prepared and their activity to inhibit a rise in serum calcium induced by parathyroid hormone in thyroparathyroidectomised rats was evaluated. Several (4-alkylidene-, 4,4-dialkyl-, or 4-alkyl-4-halopiperidinomethylene)bis(phosphonic acid) derivatives showed considerable inhibitory activity. But compounds having aromatic and polar substituents such as azido, hydroxy, amino and amido on the piperidine ring were generally inactive. In this study, two 4-alkylidene compounds (8a and 8b) and a 4,4-cyclic dialkyl compound (61) showed potent activity when administered either intravenously or perorally.
TL;DR: In this paper, the reactions of O-ethyl S-(X-phenyl) dithiocarbonates with pyrrolidine are subjected to a kinetic study in water, 250 o C, ionic strength 2 M (KCl).
Abstract: The reactions of O-ethyl S-(X-phenyl) dithiocarbonates (X=p-Cl, p-Me, and p-MeO) with a series of secondary alicyclic amines and those of the same substrates and analogous derivatives (X=H, p-NO 2 , and 2,4-(NO 2 ) 2 ) with pyrrolidine are subjected to a kinetic study in water, 250 o C, ionic strength 02 M (KCl) The reactions of piperidine and pyrrolidine show second-order kinetics (first order in amine) with the formation of a zwitterionic tetrahedral intermediate (T ± ) as the ratedetermining step The reactions of the other amines exhibit orders in amine different from one, compatible with the presence of an anionic intermediate (T - ), resulting from a kinetically important proton transfer from T ± to the amine
TL;DR: In this paper, a short, practical and diastereoselective method for preparing the ant venom alkaloid, three (3R,5S,8aS)-3-alkyl-5-methylindolizidines (1−3), has been developed.
TL;DR: 3-amino-4-methoxypyrrolidine is selected as one of the most promising C-7 substituent groups based on the QSAR analysis of azetidine quinolones to clarify the structural requirements for 3-substituted azetidines to potentiate antibacterial activity.
Abstract: Quantitative structure-activity relationships (QSAR) of various 7-(3-substituted-azetidin-1-yl)-1-cyclopropyl-6,8-difluoro-1,4-dih ydro-4- oxoquinoline-3-carboxylic acids, 14-25, were studied to clarify the structural requirements for 3-substituted azetidines to potentiate antibacterial activity A good parabolic relationship seemed to exist between the relative mean antibacterial activity indices against five representative gram-negative bacteria, GNM, and the calculated hydrophobic parameters, CLOG P, of these molecules The CLOG P value of the most potent derivative was predicted to be around 23 On the other hand, against five representative gram-positive bacteria, the relative mean antibacterial activity indices, GPM, remained high and rather constant regardless of structural variation in the azetidine moiety In order to confirm these findings, the QSAR analysis was extended with success to the quinolonecarboxylic acids, 26-34, which bear various substituted pyrrolidine, piperazine and piperidine derivatives instead of azetidines The findings showed that the introduction of any amide substituent group to these heterocyclic amine moieties would lead to marked decrease in GNM, whereas incorporation of some amino substituent groups at a position two or three carbons remote from the N-1 position resulted in great enhancement of GNM As azetidine quinolones exhibited somewhat low in vivo antibacterial activities, possibly reflecting their lesser bioavailability, we finally selected 3-amino-4-methoxypyrrolidine as one of the most promising C-7 substituent groups based on our QSAR analysis
Patent•
30 Sep 1993TL;DR: A piperidine derivative such as sufentanil is formed in a process which includes the step of condensing a piperidone with a primary amine so as to form a 4-amino-4-carboxyamino -piperidine.
Abstract: A piperidine derivative such as sufentanil is formed in a process which includes the step of condensing a piperidone with a primary amine so as to form a 4-amino-4-carboxyamino-piperidine.
TL;DR: Pyridine was rapidly reduced into piperidine with samarium diiodide in the presence of water at room temperature in excellent yield as mentioned in this paper, and pyridinecarboxamides were reduced with this system to give the corresponding methylpyridines.
Abstract: Pyridine was rapidly reduced into piperidine with samarium diiodide in the presence of water at room temperature in excellent yield. On the similar reactions of pyridine derivatives bearing chloro, amino and cyano functionalities with samarium diiodide−H 2 O−THF system, these functionalities were partly eliminated with this system to afford pyridine or piperidine. Furthermore, pyridinecarboxamides were reduced with this system to give the corresponding methylpyridines and 2-pyridinecarboxylic acid was reduced to give 2-methylpyridine as the major products
TL;DR: A practical 4-step synthesis of fibrinogen receptor antagonist MK-383, N-(n-butanesulfonyl)-O-(4-piperidinyl)-butyl)-(S)-tyrosine, is accomplished in 48% overall yield from (S)-Tyrosine.
Patent•
10 Mar 1993
TL;DR: In this paper, a novel process for preparing piperidine derivatives of formulae (I and II) wherein R1 represents hydrogen or hydroxy, R2 represents hydrogen; or R1 and R2 taken together form a second bond between the carbon atoms bearing R 1 and R 2; n is an integer of from 1 to 5; R3 is -CH2OH, -COOH or -COCalkyl; each of A is hydrogen or Hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof.
Abstract: The present invention is related to a novel process for preparing certain piperidine derivatives of formulae (I) and (II) wherein R1 represents hydrogen or hydroxy, R2 represents hydrogen; or R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2; n is an integer of from 1 to 5; R3 is -CH2OH, -COOH or -COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; each of A is hydrogen or hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof.
TL;DR: In this article, the preparation and characterization of new complexes of palladium (II) and platinum (II), with some heterocyclic containing dithiocarbamate ligands, such as piperidine-, morpholine-, and thiomorpholine-dithiocalaramate, their methyl esters and corresponding thiouramdisulphides, were reported.
TL;DR: In this article, two pathways which involve either direct nucleophilic attack of alkylamines on the imino carbon or on the sulfur α to the amino group of (arylimino)cyanomethyl alklamino disulfides are proposed to rationalize the results.
Abstract: Reactions of 5-(arylimino)-4-chloro-5H-1,2,3-dithiazoles with alkylamines such as isopropylamine, piperidine, pyrrolidine, and diethyamline in methylene chloride at room temperature gave (arylimino)-cyanomethyl alkylamino disulfides (14-83%) along with N'-aryl-N-alkylcyanoformamidines (0-88%). The yields of the latter increase and those of the former decrease with the concentration of the amine. In addition, some of the latter compounds were independently synthesized by treatment of the former with cyclic amines such as piperidine, pyrrolidine, and morpholine in methylene chloride at room temperature (22-97%). The results indicate that the former compounds are involved as intermediates in the formation of the latter in these reactions. However, when [(p-nitrophenyl)imino]cyanomethyl (pentane-1,5-diyl)amino disulfide was treated with sterically bulky amines such as tert-butyl- and diethylamines at reflux and room temperature, respectively, cyanoformamidines having a piperidine moiety rather than tert-butyl- and diethylamino groups were obtained as the only isolable products. Two pathways which involve initially either direct nucleophilic attack of alkylamines on the imino carbon or on the sulfur α to the amino group of (arylimino)cyanomethyl alkylamino disulfides are proposed to rationalize the results
TL;DR: Substitution with a methyl group in the 4 position, trans to the phosphonoacetyl group has been found to substantially increase binding affinity at the NMDA receptor complex over that of the parent compound.
TL;DR: The major role of the tropane and quinuclidine frameworks in the potency of a number of 5-HT 3 antagonists is confirmed, confirming the importance of steric hindrance for binding with the anionic receptor site.
TL;DR: The reaction of 3-bromo-2,5-thiophene-1,1-dioxides with various nucleophiles has been studied in this paper.
Abstract: The reaction of 3-bromo-2,5-thiophene-1,1-dioxides with various nucleophiles has been studied. Organolithium derivatives gave hexenynes by a 1,6-Michael addition followed by ring-opening and elimination of sulfur dioxide and lithium bromide. In a competing reaction lithium enyne sulphinates were formed. Grignard reagents gave cage compounds through a series of Michael type additions, while organocopper reagents gave 3-alkyl or 3-aryl substituted derivatives. Reaction with secondary cyclic amines in refluxing benzene resulted in a 1,4-Michael type addition to the exomethylene tautomer providing 3-bromo-6-amino-(2Z,4E)-2,4-hexadienes as main products and dialkylaminomethyl substituted cis 2,3-dihydrothiophene-1,1-dioxides. Reactions in aqueous piperidine on the other hand resulted in a normal 1,4-Michael addition producing 3-bromo-2,5-dimethyl-4-piperidino-4,5-trans-dihydrothiophene-1,1-dioxide. The reaction of the thiophene-1,1-dioxides with thiolates and alkoxides under various conditions were al...
Patent•
27 Sep 1993
TL;DR: PIPERIDINE DERIVATIVES, their preparation and their application in healthcare as discussed by the authors, their pre-parability and their applicability in health care.
Abstract: PIPERIDINE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION IN THERAPEUTICS The invention provides a compound which is a piperidine derivative of formula (I) (I)
TL;DR: Seven activated esters of indole-3-acetic acid prepared and characterized and their kinetics of aminolysis with butylamine, piperidine, and pyrrolidine in acetonitrile were investigated.
Abstract: Seven activated esters of indole-3-acetic acid (IAA) [4-oxo-1,2,3-benzotriazin-3-yl indole-3-acetate (IAA-3HBO), succinimido indole-3-acetate (IAA-NHS), 5-norbornene-1,3-dicarboximido indole-3-acetate (IAA-NHND), phthalimido indole-3-acetate (IAA-NHP), naphthalimido indole-3-acetate (IAA-NHN), 4-nitrophenyl indole-3-acetate (IAA-4NP), 8-quinolyl indole-3-acetate (IAA-8HQ)] were prepared and characterized. Their kinetics of aminolysis with butylamine, piperidine, and pyrrolidine in acetonitrile were investigated
TL;DR: In this paper, morpholine was found to give slow and incomplete Fmoc removal resulting in substantial byproduct formation in solid phase synthesis of an O-linked HIV-related glycopeptide.
TL;DR: The asymmetric total synthesis of (−)-cassine and (+)-spectaline was achieved by starting with both enantiomers of the homochiral 3-oxygenated 2,6-cis-disubstituted piperidine 3 as discussed by the authors.
TL;DR: The reaction between piperidine and Ru3(CO)12 in refluxing tetrahydrofuran gave the title compounds Ru3 (μ-H)(μ-η2-NC5H8)(CO)10 (1) and Ru(μ-C)(μ3-C), with location and refinement of the core hydrogen atoms.
TL;DR: Allylsilanes preapared from α-aminoacids react with acyl chlorides in the presence of TiCl4 to give unsaturated amino ketones, easily transformed into pyrrolidine derivatives, whereas addition to aldehydes gave 2,6 disubstituted tetrahydropyridines as discussed by the authors.