Synthesis and Stereochemistry of 3Hydroxy1,2,3,6-tetrahydropyridines (original) (raw)
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A new synthetic approach to N-substituted 1,4-dihydropyridines
Tetrahedron, 2001
AbstractÐSome novel N-substituted 1,4-dihydropyridines (DHPs) (15a±d) have been synthesized by reaction of 2-amino-5-formyl-4Hpyran (10) with primary amines. Formation of 1,4-DHPs involves ring cleavage of the 4H-pyran ring by nucleophilic attack of the respective amine and subsequent 6-exo-dig cyclization. Treatment of the pyran system 10 with hydrazines under the same reaction conditions leads, however, to the corresponding hydrazone derivatives 12a,b. Two different reaction routes are observed depending whether the amine or hydrazine derivative is used as nucleophilic reagent. A competition between 1,4 versus 1,2 addition reaction pathway is proposed. q
A new three-component domino synthesis of 1,4-dihydropyridines
Tetrahedron, 2007
Cerium ammonium nitrate (CAN) catalyzed the three-component domino reaction between aromatic amines, a,b-unsaturated aldehydes, and ethyl acetoacetate, providing an efficient new entry into 1,4-dihydropyridines. This new reaction requires very mild reaction conditions, has water as the only side product and is complementary to the classical Hantzsch synthesis in that it is well suited to the preparation of N-aryl-5,6-unsubstituted dihydropyridines. Experiments in the presence of a radical trap suggest that a one-electron oxidative mechanism can be excluded and that CAN acts as a Lewis acid.
PREPARATION OF NEW 1,4-DIHYDROPYRIDINES
ln the last two decades considerable attention has been paid to the development of a very heterogeneous group of drugs whose pharmacological activity derives from their capacity to block potential-dependent transmembrane ion channels, that are opened during depolarization and mainly located in cardiac and vascular smooth muscle. These are the so-called calcium antagonists which are mainly used in clinical practice as anti-anginal and antihypertensive agents (1,2). The most important group of these drugs is that of 1,4-dihydropyridines (DHP), whose principal representative, nifedipine, has been subjected to many structural manipulations oriented towards obtaining more potent and selective agents or achieving more prolonged effects. Together with their useful pharmacological activ¡ties, 1 ,4-DH P show a number of other effects, namely, spasmo-lit¡c (3), antihistaminic (4), antiulcer (5), anti-inflammatory (6), PAF antagonistic (7), which could also be therapeutically useful if potentiation of any of these capacities could be attained. Revising the great number of structures reported for the previously prepared 1,4-DHP derivatives and considering the main structure-activity relationships described for Caantagonist and antihypertensive activities, we planned to ascerta¡n the role of the 4-phenyl substituent on those secondary effects and if they were intrinsically dependent on the existence of the 1,4-DHP moiety. ln this work we describe the preparation of three series of 1,4-DHP having methylthioethyl, methylsulfinylethyl and methylsulfonylethyl chains rather than the typical phenyl substituted ring at position 4 of the dihydropyridine.
Archiv der Pharmazie, 2010
A series of twenty new 4‐substituted‐2,6‐dimethyl‐3,5‐bis‐N‐(heteroaryl)‐carbamoyl‐1,4‐dihydropyridines have been prepared from a three‐component one‐pot condensation reaction of N‐heteroaryl acetoacetamide, an aromatic/heteroaromatic aldehyde, and ammonium acetate under four different experimental conditions. Except for the conventional method, all the experimental conditions were simple, eco‐friendly, economical, and the reactions were rapid and high‐yielding. The methods employed have been compared in terms of yields, cost, and simplicity. The synthesized compounds were characterized by different spectroscopic techniques and evaluated for their in‐vitro anticancer, antibacterial, and antitubercular activities. Amongst the compounds tested, compound 25 exhibited the highest anticancer activity while compounds 14 and 18 exhibited significant antibacterial and antitubercular activities.
Tetrahedron, 2008
An organocatalysed protocol for one-pot synthesis of 1,4-dihydropyridines via three-component coupling of cinnamaldehyde, aniline and bketo esters under solvent free conditions at ambient temperature is reported. The reaction is generally very fast and the products are obtained in high yield. The catalytic activity of small organic molecules like amino acids (acidic, basic and neutral), ephedrine and cinchona alkaloids was studied.
Organocatalyzed Synthesis and Antifungal Activity of Fully Substituted 1,4-Dihydropyridines
ChemistrySelect, 2018
An efficient one-pot four-component domino reaction for the convenient access of fully diversified 1,4-dihydropyridines (1,4-DHPs) from simple starting materials using basic organocatalyst is demonstrated. These derivatives were synthesized in good to excellent yields via the reaction between dialkyl acetylenedicarboxylates, arylamines, malononitrile, and aromatic aldehydes catalyzed by 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) in ethanol at room temperature. The molecular structure of 1,4-DHP derivative 5 h was confirmed by the single crystal X-ray analysis. Mild reaction conditions, short reaction time, applicable to a broad range of substrates and simple experimental procedure are some of the salient features of the present protocol. In addition, the synthesized compounds were screened against Aspergillus niger (MTCC-281), Aspergillus fumigates (MTCC-343) and Claviceps purpure for in vitro antifungal activity and noted that most of the compounds were exhibit good to excellent antifungal activities compared to the standard reference.
Synthesis and Heterocyclization of 1-Aryl-2-methyl-4-oxo-1,4,5,6-tetrahydropyridine-3-carboxylates
Journal of Heterocyclic Chemistry, 2017
A series of novel isoxazole, dihydropyrazolone, and tetrahydropyridine derivatives were synthesized by the reaction of corresponding ethyl 1-substituted aryl-2-methyl-4-oxo-1,4,5,6-tetrahydropyridine-3-carboxylates with different hydrazines and hydroxylamine. Reaction of tetrahydropyridone with N,N-dimethylformamide dimethyl acetal provided 1-(5-chloro-2-methylphenyl)-2-[2-(dimethylamino)ethenyl]-4-oxo-1,4,5,6tetrahydropyridine-3-carboxylate, which was cyclized into a bicyclic compound on treatment with ammonium acetate. The structures of all synthesized compounds were confirmed by IR, 1 H NMR, and 13 C NMR spectroscopy data. The structure of 5-(5-chloro-2-methylphenyl)-4-methyl-2-phenyl-2,5,6,7-tetrahydro-3H-pyrazolo [4,3-c]pyridin-3-one was unambiguously assigned by means of X-ray analysis data.
Synthesis and structural study of new highly lipophilic 1,4-dihydropyridines
New Journal of Chemistry, 2005
A new series of 1,4-dihydropyridines (1,4-DHPs) endowed with ester groups bearing long and functionalised alkoxy chains at the C3 and C5 positions of the nitrogen ring have been prepared from the corresponding b-keto esters which were in turn prepared by a lipase catalysed transesterification reaction. The structural study has been carried out by X-ray crystallography and theoretical calculations at the semiempirical (AM1), ab initio (HF/6-31G*) and B3LYP/6-31G* levels and reveals that the long alkyl chains do not have any influence on the required geometry of the 1,4-DHPs for biological activity. However, these chains have a strong impact on the lipophilicity and, therefore, they could be used to gain a better control of the duration of the pharmacological action.