- Markovnikov Wacker-Tsuji Oxidation of Allyl(hetero)arenes and Application in a One-Pot Photo-Metal-Biocatalytic Approach to Enantioenriched Amines and Alcohols
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The Wacker-Tsuji aerobic oxidation of various allyl(hetero)arenes under photocatalytic conditions to form the corresponding methyl ketones is presented. By using a palladium complex [PdCl2(MeCN)2] and the photosensitizer [Acr-Mes]ClO4 in aqueous medium and at room temperature, and by simple irradiation with blue led light, the desired carbonyl compounds were synthesized with high conversions (>80%) and excellent selectivities (>90%). The key process was the transient formation of Pd nanoparticles that can activate oxygen, thus recycling the Pd(II) species necessary in the Wacker oxidative reaction. While light irradiation was strictly mandatory, the addition of the photocatalyst improved the reaction selectivity, due to the formation of the starting allyl(hetero)arene from some of the obtained by-products, thus entering back in the Wacker-Tsuji catalytic cycle. Once optimized, the oxidation reaction was combined in a one-pot two-step sequential protocol with an enzymatic transformation. Depending on the biocatalyst employed, i. e. an amine transaminase or an alcohol dehydrogenase, the corresponding (R)- and (S)-1-arylpropan-2-amines or 1-arylpropan-2-ols, respectively, could be synthesized in most cases with high yields (>70%) and in enantiopure form. Finally, an application of this photo-metal-biocatalytic strategy has been demonstrated in order to get access in a straightforward manner to selegiline, an anti-Parkinson drug. (Figure presented.).
- Albarrán-Velo, Jesús,Gotor-Fernández, Vicente,Lavandera, Iván
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supporting information
p. 4096 - 4108
(2021/08/19)
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- Selegiline hydrochloride synthesis process
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The invention relates to the field of chemical pharmacy, particularly to a selegiline hydrochloride preparation method. According to the invention, the method avoids the use of ephedrine, pseudoephedrine, deoxyephedrine and other management and control products, has characteristics of inexpensive and easily-available raw materials, short synthesis route, safe and environmentally-friendly production and synthesis cost reducing, can obtain the high-purity target compound at high yield, and is suitable for industrial large-scale production.
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- Preparation method of selegiline
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The invention provides a preparation method of selegiline. The method comprises the steps of carrying out an acyl chlorination reaction on a compound (i), carrying out an acylation reaction on the compound (i) and benzene, and carrying out a propargylation reaction after carbonyl reduction and deacylation to obtain selegiline, wherein in the compound (i), R represents methyl or ethyl or trifluoromethyl or phenyl or benzyl. According to the method, an acyl-D-N-methylalanine compound is used as a raw material and subjected to acylation, carbonyl reduction, the deacylation reaction and the propargylation reaction to obtain the selegiline, not only is the raw material simple and easy to obtain, but also there are few reaction steps, the operation is simple and convenient, and dangerous or high-price reagent raw materials do not need to be used. Meanwhile, according to the method, chiral resolution of an intermediate or a final product is not needed, the ee value of the product is high, theyield is high, and the method is suitable for large-scale and industrial production.
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Paragraph 0058; 0062-0065; 0069-0072; 0076-0078
(2019/08/14)
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- METHOD FOR PREPARING SELEGILINE BASE
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The present invention relates to a process for the preparation of selegiline base, an irreversible and selective inhibitor of the MAO-B enzymes and which is used in the treatment of Parkinson's Disease.
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Paragraph 0040
(2018/08/12)
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- A concise enantioselective synthesis of (R)-selegiline, (S)-benzphetamine and formal synthesis of (R)-sitagliptin via electrophilic azidation of chiral imide enolates
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A concise and high yielding enantioselective synthesis of (R)-selegiline, an anti-Parkinson's drug, (S)-benzphetamine, an anti-obesity agent, and (S)-sitagliptin, an anti-diabetic drug has been described starting from commercially available starting materials employing Evans' electrophilic azidation of chiral imide enolates as a key chiral inducing step, which proceeds in a highly diastereoselective manner (>99%).
- Dey, Soumen,Sudalai, Arumugam
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- Synthesis of novel 1,4-disubstituted 1,2,3-triazolo-bosentan derivatives - evaluation of antimicrobial and anticancer activities and molecular docking
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Novel 1,4-disubstituted 1,2,3-triazolo bosentan derivatives 1a-n from bosentan 2 were synthesized in good yields by sequential chlorination, azidation followed by Cu(i) catalyzed 1,3-dipolar cycloaddition. All obtained compounds 1a-n were evaluated for their antimicrobial and in vitro anticancer activities and by in silico docking studies. Among all tested compounds 1e,f and 1h-j show better antimicrobial activities against the tested bacteria and fungi. When subjected to anticancer testing, compounds 1g-j and 1n show significant activities against both A549 and SKOV-3 cell lines with IC50 values at 7.81 μg mL-1 and among them compound 1i exhibited very potent activity. In addition, no toxicity was calculated up to 2 mg mL-1 in Vero cells. In silico studies were conducted to investigate the possible bonding modes of 1a-n with target receptors namely DNA topoisomerase IV (4 EMV) and anaplastic lymphoma kinase (2XP2). Among them, compounds 1e and 1h show maximum binding energies with 4EMV and 2XP2 receptors, respectively which also exhibited good antimicrobial and potent anticancer activities.
- Easwaramoorthi,Rajendran, A. Jeya,Rao, K. Chennakesava,Arun,Balachandran,Perumal,Emi, Nobuhiko,Mahalingam,Duraipandiyan,Al-Dhabi
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p. 105266 - 105278
(2015/12/30)
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- A short enantioselective synthesis of ephedrine, amphetamine and their analogues via two stereocentered Co(III)-catalyzed hydrolytic kinetic resolution of racemic syn-benzyloxy epoxide
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An efficient route for the synthesis of 6 drugs belonging to phenethylamine and amphetamine classes in excellent overall yields and high optical purity has been described. The strategy involves introduction of stereogenic centers by means of two-stereocentered Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of racemic syn-benzyloxy epoxide followed by Pd-catalyzed regioselective cationic hydrogenation of amino alcohols as the key reactions.
- Lalwani, Komal G.,Sudalai, Arumugam
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p. 6488 - 6490
(2015/11/16)
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- Selegiline-functionalized, PEGylated poly(alkyl cyanoacrylate) nanoparticles: Investigation of interaction with amyloid-β peptide and surface reorganization
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Alzheimer's disease (AD) is a neurodegenerative disorder for which the research of new treatments is highly challenging. Since the fibrillogenesis of amyloid-β peptide 1-42 (Aβ1-42) peptide is considered as a major cause of neuronal degeneration, specific interest has been focused on aromatic molecules for targeting this peptide. In this paper, the synthesis of selegiline-functionalized and fluorescent poly(alkyl cyanoacrylate) nanoparticles (NPs) and their evaluation for the targeting of the Aβ1-42 peptide are reported. The synthetic strategy relied on the design of amphiphilic copolymers by tandem Knoevenagel-Michael addition of cyanoacetate derivatives, followed by their self-assembly in aqueous solutions to give the corresponding NPs. Different cyanoacetates were used: (i) hexadecyl cyanoacetate (HDCA) to form the hydrophobic core of the NPs; (ii) rhodamine B cyanoacetate (RCA) for fluorescent purposes; (iii) methoxypoly(ethylene glycol) cyanoacetate (MePEGCA) for stealth properties and (iv) selegiline-poly(ethylene glycol) cyanoacetate (SelPEGCA) to obtain the desired functionality. Two different amphiphilic copolymers were synthesized, a selegiline-containing copolymer, P(MePEGCA-co-SelPEGCA-co-HDCA), and a rhodamine-labelled counterpart, P(MePEGCA-co-RCA-co-HDCA), further blended at variable ratios to tune the amount of selegiline moieties displayed at the surface of the NPs. Optimal formulations involving the different amphiphilic copolymers were determined by the study of the NP colloidal characteristics. Interestingly, it was shown that the zeta potential value of the selegiline-functionalized nanoparticles dramatically decreased, thus emphasizing a significant modification in the surface charge of the nanoparticles. Capillary electrophoresis has then been used to test the ability of the selegiline-functionalized NPs to interact with the Aβ1-42 peptide. In comparison with non functionalized NPs, no increase of the interaction between these functionalized NPs and the monomeric form of the Aβ1-42 peptide was observed, thus highlighting the lack of availability of the ligand at the surface of the nanoparticles. A mechanism explaining this result has been proposed and was mainly based on the burial of the hydrophobic selegiline ligand within the nanoparticles core.
- Le Droumaguet, Benjamin,Souguir, Hayfa,Brambilla, Davide,Verpillot, Romain,Nicolas, Julien,Taverna, Myriam,Couvreur, Patrick,Andrieux, Karine
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experimental part
p. 453 - 460
(2012/02/16)
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- An organo-catalytic approach to the enantioselective synthesis of (R)-selegiline
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An efficient enantioselective synthesis of (R)-selegiline has been achieved by two routes, via proline-catalyzed α-aminooxylation as well as α-amination of phenylpropanaldehyde as the key step.
- Talluri, Siva Kumar,Sudalai, Arumugam
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p. 9758 - 9763
(2008/02/12)
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- Asymmetric synthesis of l-DOPA and (R)-selegiline via, OsO 4-catalyzed asymmetric dihydroxylation
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A simple and effective procedure for the enantioselective synthesis of two important neurotransmitter drugs, that is, (S)-3,4-dihydroxyphenylalanine (l-DOPA) and (R)-N,α-dimethyl-N-2-propynylbenzeneethaneamine [(R)-selegiline], is described by employing the Sharpless asymmetric dihydroxylation (AD) as a key step to introduce chirality.
- Sayyed, Iliyas Ali,Sudalai, Arumugam
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p. 3111 - 3116
(2007/10/03)
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- A simple procedure for af-propenylation and af-propynylation of secondary amines
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A number of tertiary N-allyl- and N-propargyl-substituted amines have been prepared by alkylation of secondary amines under solid-liquid phase-transfer catalysis conditions.
- Crock, Piero Dalla,Ferraccioli, Raffaella,Rosa, Concetta L.A.
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p. 107 - 109
(2007/10/03)
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- Enantiomer separation via diastereoisomeric salt formation and liquid-liquid phase transition
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On reacting racemic amine bases with half equivalent amount of sodium-hydrogen-tartrate in a water-benzene solvent system, the mixed-neutral tartrate accumulates in the aqueous phase, while the free base concentrates in the organic phase, resulting in enantiomer separation without crystallization.
- Acs, Maria,Kozma, David,Fogassy, Elemer
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p. 475 - 478
(2007/10/02)
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- Process for the preparation of propargyl amines
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The invention relates to a new process for the preparation of propargyl ammonium chlorides of the Formula I STR1 by alkaline decomposition of the d-tartarate of the 1-isomer of an amine of the Formula II STR2 and subsequent reaction of the amine of the Formula II with a halide of the Formula III in the presence of an organic solvent, alkali and water in which in Formulae II and III respectively, n is 1 or 0 and X stands for halogen which comprises reacting the d-tartarate of the 1-isomer of an amine of the Formula II in aqueous suspension with an alkali, dissolving the base of the Formula II, thus set free without isolation in a water non-miscible organic solvent and reacting the same in the said phase with a halide of the Formula III, and thereafter--preferably after separating the aqueous layer--reacting the mixture which contains the amines of the Formulae II and IV STR3 in the organic phase in the presence of water with an organic acid or a solution which has a pH value of 1.5-6 and consists of an inorganic acid and water, thus dissolving in the two-phase mixture formed the salt of the amine of the Formula II in the aqueous layer and selectively separating the amine of the Formula II from the amine of the Formula IV, and thereafter adding after the separation of the phases hydrogen chloride to the amine of the Formula IV being in the organic phase and thus precipitating the salt of the Formula I. The compounds of Formula I are known pharmaceutical active ingredients. The advantage of the process of the present invention that it is highly economical and enables the recovery of the starting materials on large scale production too.
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