Showing papers on "Piperidine published in 2003"
TL;DR: The most recent applications of the ring-closing metathesis reaction (RCM) to construct piperidine and pyrrolidine cores for the total synthesis of natural alkaloids are described in this paper.
396 citations
TL;DR: Preliminary mechanistic studies showed that the reaction occurred by direct, irreversible, anti-Markovnikov hydroamination and that the mechanism of the ruthenium-Catalyzed hydroamination is likely to be distinct from that of the recently reported rhodium-catalyzed reaction.
Abstract: The transition metal-catalyzed anti-Markovnikov hydroamination of unactivated vinylarenes with a rhodium complex of DPEphos is reported The reaction of electron−neutral or electron-rich vinylarenes with a variety of secondary amines in the presence of catalyst forms the products from anti-Markovnikov hydroamination in high yields Reactions of morpholine, N-phenylpiperazine, N-Boc-piperazine, piperidine, 2,5-dimethylmorpholine, and perhydroisoquinoline reacted with styrene to form the amine product in 51−71% yield Reactions of a variety of vinylarenes with morpholine generated amine as the major product Reactions of morpholine with electron-poor vinylarenes gave lower amine:enamine ratios than reactions of electron-rich vinylarenes at the same concentration of vinylarene, but conditions were developed with lower concentrations of electron-poor vinylarene to maintain formation of the amine as the major product Reactions of dimethylamine with vinylarenes were fast and formed amine as the major product
204 citations
TL;DR: The enantioselective synthesis of 2-alkylpiperidines and cis- and trans-2,6-dialkylpiperidine is reported and the potential of this approach is illustrated.
Abstract: Starting from a common lactam, (3R,8aS)-5-oxo-3-phenyl-2,3,6,7,8,8a-hexahydro-5H-oxazolo[3,2-a]pyridine (1), or its enantiomer, the enantioselective synthesis of 2-alkylpiperidines and cis- and trans-2,6-dialkylpiperidines is reported. The potential of this approach is illustrated by the synthesis of the piperidine alkaloids (R)-coniine, (2R,6S)-dihydropinidine, (2R,6R)-lupetidine, and (2R,6R)-solenopsin A, the indolizidine alkaloids (5R,8aR)-indolizidine 167B and (3R,5S,8aS)-monomorine I, and the nonnatural base (4R,9aS)-4-methylquinolizidine.
133 citations
TL;DR: In this article, the synthesis of a series of epoxy 5-phenylmorphans is explored in order to determine the conformational requirements of the phenolic ring in a phenylmorphan molecule that may be needed both for binding to a specific opioid receptor and for exhibiting opioid agonist or antagonist activity.
Abstract: The synthesis of a series of epoxy 5-phenylmorphans is being explored in order to determine the conformational requirements of the phenolic ring in a phenylmorphan molecule that may be needed both for binding to a specific opioid receptor and for exhibiting opioid agonist or antagonist activity. Of the twelve possible ortho- and para-bridged isomers (a–f) (Fig. 1), we now report the synthesis of the para-d isomer, rac-(3R,6aS,11aR)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocin-8-ol (3). Compound 3 was synthesized via construction of the 5-phenylazabicyclo[3.3.1]non-3-ene skeleton (Scheme 1) and subsequent closure of the epoxy bridge (Scheme 2). As determined by an X-ray diffraction study, the epoxy bridge, restricting the phenyl-ring rotation, fixed the dihedral angle between the least-squares planes through the phenyl ring and atoms N(2), C(3), C(11a), and C(6a) of the piperidine ring (Fig. 2) at 43.0°, and the torsion angle C(12)C(6a)C(6b)C(10a) at −95.0°.
130 citations
TL;DR: It appears that changing the five-, to four- to a three-membered ring results in a drop of activity against influenza A virus.
115 citations
Patent•
07 Oct 2003TL;DR: In this paper, the use of a compound of formula (I) in the manufacture of a medicament for use in the inhibition of 11βHSD1 was described, and the compound was used in the synthesis of a new drug.
Abstract: The use of a compound of formula (I) in the manufacture of a medicament for use in the inhibition of 11βHSD1 is described.
95 citations
TL;DR: The PdCl(2)-catalyzed cyclization of amino allylic alcohol 16 gave the cyclized product 17a with excellent diastereoselectivity and the versatility of compound 17a as the building block for synthesizing cis-2,6-disubstituted piperidine alkaloids has been demonstrated.
82 citations
TL;DR: In this paper, a method of synthesis of potentially physiologically active compounds, 1′-substituted 6-amino-spiro-4-(piperidine-4′)-2H,4H-pyrano[2,3-c]pyrazoles, was developed.
69 citations
TL;DR: Examination of oligodeoxyribonucleotide duplexes bearing a site-specific cross-link of the transplatin analogue containing the piperidine ligand indicates that in contrast to transplatin, trans-(PtCl2(NH3)(piperidine)) forms stable 1,3-intrastrand cross-links in double-helical DNA that distort DNA and are not readily removed from DNA by nucleotide excision repair system.
61 citations
TL;DR: In this article, the direct formation of β-l-rhamnopyranosides by means of thioglycoside donors protected with a 2-O-sulfonate ester and, ideally, a 4 O-benzoyl ester was reported.
60 citations
Patent•
06 Aug 2003TL;DR: In this article, the compounds of a certain formula (1), in which the given substituents have the meanings as indicated in the description, are novel effective PDE4 inhibitors.
Abstract: The compounds of a certain formula (1), in which the given substituents have the meanings as indicated in the description, are novel effective PDE4 inhibitors.
TL;DR: Secondary beta deuterium isotope effects on acidity constants of ammonium ions are measured using a remarkably precise NMR titration method and it is found that deuteration is more effective when antiperiplanar to a lone pair.
Abstract: Secondary β deuterium isotope effects on acidity constants of ammonium ions are measured using a remarkably precise NMR titration method. Deuteration is found to increase the basicity of methylamine, dimethylamine, benzylamine, and N,N-dimethylaniline. The effect is attributed to a lowered zero-point energy of a CH bond adjacent to an amine nitrogen. The method permits a determination of the stereochemical dependence of the isotope effect in a locked piperidine, and it is found that deuteration is more effective when antiperiplanar to a lone pair. The values are consistent with a cos2 dependence on dihedral angle, with no detectable angle-independent inductive effect.
TL;DR: Asymmetric total synthesis of (+)-1-deoxynojirimycin (1) and (+)-castanospermine (2) was described in this article.
Patent•
06 Aug 2003
TL;DR: In this article, the compounds of a certain formula (1), in which the given substituents have the meanings as indicated in the description, are novel effective PDE4 inhibitors.
Abstract: The compounds of a certain formula (1), in which the given substituents have the meanings as indicated in the description, are novel effective PDE4 inhibitors.
Patent•
06 Aug 2003TL;DR: In this paper, the compounds of a certain formula (1), in which the given substituents have the meanings as indicated in the description, are novel effective PDE4 inhibitors.
Abstract: The compounds of a certain formula (1), in which the given substituents have the meanings as indicated in the description, are novel effective PDE4 inhibitors.
Patent•
30 Apr 2003TL;DR: In this paper, the authors present a survey of the use of new PIPERIDINE 4-ALKENYL DERIVATIVES for the treatment of HIV and AIDS.
Abstract: THIS INVENTION PROVIDES COMPOUNDS HAVING DRUG AND BIO-AFFECTING PROPERTIES, THEIR PHARMACEUTICAL COMPOSITIONS AND METHOD OF USE. IN PARTICULAR, THE INVENTION IS CONCERNED WITH NEW PIPERIDINE 4-ALKENYL DERIVATIVES THAT POSSESS UNIQUE ANTIVIRAL ACTIVITY. MORE PARTICULARLY, THE PRESENT INVENTION RELATES TO COMPOUNDS USEFUL FOR THE TREATMENT OF HIV AND AIDS. THE COMPOUNDS OF THE INVENTION FOR THE GENERAL FORMULA I: WHEREIN: Q IS SELECTED FROM THE GROUP CONSISTING OF: -W- IS
TL;DR: The reactions between the cyclic sec. amines pyrrolidine and piperidine with B(C6F5)3 yield Lewis acid-base adducts with both intra- and inter-molecular hydrogen bonding interactions between C-H and N-H groups and aryl-fluorines in the solid state.
TL;DR: In this paper, the synthesis of novel 7-(4-halophenyl)-8,9-dihydro-7H-12-oxa-9,11-diaza-benzo[a]anthracene derivatives has been reported.
Abstract: The synthesis of novel 7-(4-halophenyl)-8,9-dihydro-7H-12-oxa-9,11-diaza-benzo[a]anthracene derivatives has been reported. The key intermediate 3-amino-9-chloro-1-(4-halophenyl)-1H-benzo[h]chromene-2-carbonitrile (3) was obtained by treating 4-halobenzylidenmalononitriles (1a-c) and ethyl 4-halobenzylidenmalonates (1d-f) with 4-chloro-1-naphthol (2) in ethanolic piperidine solution. Antimicrobial activity was shown for most of the synthesized compounds.
TL;DR: The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacokinetics.
TL;DR: In this article, 27 11C-labeled amides were synthesized using [11C] carbon monoxide in low concentrations, palladium(0), organohalides and amines in a small micro-autoclave (200 μL).
Patent•
25 Jun 2003
TL;DR: Piperidine derivatives and pharmaceutically acceptable derivatives of formula (I) thereof are useful in methods of treatment of bacterial infections in mammals, particularly in man as discussed by the authors, where RA is an optionally substituted bicyclic carbocyclic or heter-cyclic ring system of structure.
Abstract: Piperidine derivatives and pharmaceutically acceptable derivatives of formula (I) thereof useful in methods of treatment of bacterial infections in mammals, particularly in man. Wherein: RA is an optionally substituted bicyclic carbocyclic or heterocyclic ring system of structure (i), and R4 is a group -U-R5 where U is selected from CO, SO2 and CH2 and R5 is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (A).
TL;DR: A new major urinary metabolite was detected in rat urine and plasma using HPLC and has a unique structure compared to the previously reported metabolites in that it retains methylenedioxy ring and conjugated double bonds while the piperidine ring is modified to form propionic acid group.
TL;DR: In this paper, 5-hydroxy-2-piperidones (−)-6b and (−)-18 were prepared from 2-azetidinones via two-carbon ring homologation.
Journal Article•
TL;DR: In this paper, arylmethylene of benzopyrane or benzothiopyrane 3,4 has been synthesized and condensed with hydrazine, guanidine and thiourea to yield pyrazole 5-8, aminopyrimidine 9,10 and thioxopyridine derivatives 11,12, respectively.
Abstract: The arylmethylene of benzopyrane or benzothiopyrane 3,4 have been synthesized and condensed with hydrazine, guanidine and thiourea to yield pyrazole 5-8, aminopyrimidine 9,10 and thioxopyrimidine derivatives 11,12, respectively. Compounds 3 or 4 on treatment with malononitrile in the presence of ammonium acetate/acetic acid or in the presence of piperidine/ methanol to yield benzopyrano- and benzothiopyranopyridine 13,14 and benzopyrano- and benzothiopyrane 15,16, respectively. The oxirane of compound 3 is prepared and condensed with CS 2 to yield the tricyclic system, thioxothienobenzopyrane 21. Ylidenemalononitrile for the ketone 1 and 2 are synthesized and condensed with aromatic aldehyde in presence of ammonium acetate/acetic acid to yield benzopyranopyridine and benzothiopyranopyridine derivatives 24,25, respectively, which are the isomer of compounds 13,14. Ylidenemalononitrile on condensation with phenylisothiocyanate yields benzo-pyrano- and benzothiopyranothioxopyridine 28,29, respectively.
TL;DR: An efficient solution-phase parallel synthesis of a library of 3,5,7-trisubstituted [1,2,3]triazolo[4,5-d]pyrimidines is described in this paper.
Abstract: An efficient solution-phase parallel synthesis of a library of 3,5,7-trisubstituted [1,2,3]triazolo[4,5-d]pyrimidines is described. Monosubstituted amidines may be converted to 2-substituted 5-amino-4,6-dihydroxypyrimidines in four steps. Treatment with a primary amine followed by cyclization yields the 7-chloro-3,5-disubstituted [1,2,3]triazolo[4,5-d]pyrimidines as penultimate intermediates. Final nucleophilic substitution of the 7-chloro group with an excess of a primary or secondary amine, a hydrazine or a O-alkylhydroxylamine proceeds efficiently. Scavenging of the excess amine with a resin-bound isocyanate in the presence of resin-bound piperidine as a base affords the desired 3,5,7-trisubstituted [1,2,3]triazolo[4,5-d]pyrimidines in good yields and purities.
TL;DR: In this paper, piperidine-based amino alcohols were applied to catalyze enantioselective addition of diethyl zinc to aldehydes, high asymmetric induction was observed with 4c and 4e, and the ee value was up to 98%.
Abstract: β-Amino alcohols 4a – e were easily prepared from l -phenylalanine in three simple straightforward steps. The key intermediate compound ( S )- 3 was achieved in high yield (up to 92%) with glutaraldehyde and NaBH 4 /H 2 SO 4 in THF at room temperature. These five ligands were applied to catalyze enantioselective addition of diethyl zinc to aldehydes, high asymmetric induction was observed with 4c and 4e , and the ee value was up to 98%. The effect of the substitutes on the nitrogen atom was also observed via comparing piperidine-based amino alcohols with pyrrolidine-based similar ligands.
Patent•
09 Oct 2003
TL;DR: In this article, a method to inhibit p38-α kinase using compounds which are azaindoles wherein the azain doles are coupled through a piperidine or piperazine type linker to another cyclic moiety was proposed.
Abstract: The invention is directed to methods to inhibit p38 kinase, preferably p38-α using compounds which are azaindoles wherein the azaindoles are coupled through a piperidine or piperazine type linker to another cyclic moiety.
TL;DR: In this article, the enantiopure β-amino esters were reduced to β-amnio alcohol, which was then condensed with 2,4-pentadione to obtain cyclic enamine, and hydrogenated to deliver all cis-2,3,6-trisubstituted piperidine.
TL;DR: In this paper, the stereoselective synthesis of piperidine alkaloids deoxymannojirimycin and d -mannolactam from d -serine has been achieved.
TL;DR: It is established that the configuration at C-5 of the piperidine ring plays a major role in controlling the stereochemical outcome and a short stereocontrolled synthesis of (+)-deoxoprosophylline is achieved using this chemistry.
Abstract: The synthesis of 3,4,6-tri-O-acetyl imino D-glucal 2 from D-glucal is reported. This imino glycal participates in a variety of Lewis acid mediated carbon–carbon bond forming reactions by allylic displacement of the C-3 acetate group by added nucleophiles. Allyl silanes, trimethylsilyl enol ethers, alkenes and dialkyl zinc reagents serve as suitable reaction partners. In all the cases studied, the β-anomer is predominant. Using imino glycal 8, epimeric at C-5, it is established that the configuration at C-5 of the piperidine ring plays a major role in controlling the stereochemical outcome. These results are rationalised by invoking the intermediacy of a conjugated N-acyliminium ion. A short stereocontrolled synthesis of (+)-deoxoprosophylline is achieved using this chemistry. Additionally, imino glucal 2 is transformed into bromo piperidine 16, whose X-ray crystal structure is determined. Bromide 16 participates in palladium catalysed Stille and Suzuki cross-couplings allowing access to C-2 substituted imino sugars 17 and 18. In other studies, imino sugar C-glycosides 21 and 22 are made by combining the Lewis acid mediated carbon–carbon bond forming reactions with stereospecific dihydroxylations.