Synthesis of 1,2-Diamino-1-phenylpropane Diastereoisomers from u-N-Trifluoroacetyl-2-amino-1-phenylpropan-1-ol

Dufrasne, François; Nève, Jean

doi:10.1007/s00706-004-0266-7

Cited by 5 publications

(6 citation statements)

References 17 publications

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“…The starting alcohols 9 and 10 were transformed into their mesylate derivatives in good yields by adding methanesulfonyl chloride at room temperature in the presence of triethylamine. Mesylate groups were then converted into azidoalkanes to give compounds 13 and 14 , which were hydrogenated using Pd/C as catalyst to create compounds 4 and 15 (Scheme ) …”

Section: Resultsmentioning

confidence: 99%

Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors

et al. 2010

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Oxidized low-density lipoproteins (LDLs) accumulate in the vascular wall and promote local inflammation, which contributes to the progression of the atheromatous plaque. The key role of myeloperoxidase (MPO) in this process is related to its ability to modify APO B-100 in the intima and at the surface of endothelial cells. A series of 3-(aminoalkyl)-5-fluoroindole analogues was designed and synthesized by exploiting the structure-based docking of 5-fluorotryptamine, a known MPO inhibitor. In vitro assays were used to study the effects of these compounds on the inhibition of MPO-mediated taurine chlorination and oxidation of LDLs. The kinetics of the interaction between the MPO redox intermediates, Compounds I and II, and these inhibitors was also investigated. The most potent molecules possessed a 4- or 5-carbon aminoalkyl side chain and no substituent on the amino group. The mode of binding of these analogues and the mechanism of inhibition is discussed with respect to the structure of MPO and its halogenation and peroxidase cycles.

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Section: Resultsmentioning

confidence: 99%

Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors

et al. 2010

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“…Based on the mass spectral evidence and the relative elution behavior of TFAA derivatives of methamphetamine and ephedrine reported by Lin and Lua (19), we hypothesized that this peak was due to N , O ‐bis(trifluoroacetyl)ephedrine. Epimerization of N‐ trifluoroacetylated derivatives of norephedrine have been reported (20), which provides precedent for this proposal.…”

Section: Resultsmentioning

confidence: 89%

Formation of Trifluoroacetylated Ephedrine During the Analysis of a Pseudoephedrine‐Formaldehyde Adduct by TFAA Derivatization Followed by GC‐MS

Abdullah

Miskelly

2009

Journal of Forensic Sciences

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(+)-Pseudoephedrine reacts with formaldehyde to form (4S,5S)-3,4-dimethyl-5-phenyloxazolidine. Gas chromatography-mass spectrometry (GC-MS) analysis after the reaction of this oxazolidine with excess trifluoroacetic acid anhydride (TFAA) shows predominantly N,O-bis(trifluoroacetyl)pseudoephedrine with some of the monotrifluoroacetylated derivative. In addition, variable amounts of N,O-bis(trifluoroacetyl)ephedrine were detected by GC-MS. N,O-bis(trifluoroacetyl)ephedrine was not detected upon trifluoroacetylation of the source (+)-pseudoephedrine, and nuclear magnetic resonance analysis of the (4S,5S)-3,4-dimethyl-5-phenyloxazolidine showed no evidence of the (4R,5S) isomer. This suggests that the N,O-bis(trifluoroacetyl)ephedrine is formed by epimerization during the TFAA derivatization and GC-MS analysis of the pseudoephedrine-formaldehyde adduct.

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“…27,30 The hydroxyl groups in these compounds were transformed first into mesylate in the presence of methanesulfonyl chloride and amino-basic compound to give 11−19 (Scheme 2). 31 Mesylate groups in 11−14, 17, and 19 were then converted into azidoalkane by adding NaN 3 in DMSO at 100 °C to give 20−25 in good yields. 31 These azidoalkane compounds were hydrogenated by use of LiAlH 4 (or C/Pd for 22 and 25) to create 26−30 and 46 (Scheme 2).…”

Section: ■ Chemistrymentioning

confidence: 99%

“…31 Mesylate groups in 11−14, 17, and 19 were then converted into azidoalkane by adding NaN 3 in DMSO at 100 °C to give 20−25 in good yields. 31 These azidoalkane compounds were hydrogenated by use of LiAlH 4 (or C/Pd for 22 and 25) to create 26−30 and 46 (Scheme 2). 32 Starting from mesylate compounds 11, 12, 15, and 16, products 31−45 were obtained via the same synthetic method but under different conditions (Scheme 3).…”

Section: ■ Chemistrymentioning

confidence: 99%

“…A series of 3-(hydroxyalkyl)indole derivatives, 1 – 6 and 8 – 10 , was obtained following a general procedure based on Fischer indole synthesis, starting from commercially available phenylhydrazine hydrochloride derivatives and either cyclic enol ether ( 1 – 6 ) or 6-hydroxyhexanal ( 7 ), which was obtained by the reduction of ε-caprolactone by use of DIBAL-H as indicated in Scheme ( 8 – 10 ). , The hydroxyl groups in these compounds were transformed first into mesylate in the presence of methanesulfonyl chloride and amino-basic compound to give 11 – 19 (Scheme ) . Mesylate groups in 11 – 14 , 17, and 19 were then converted into azidoalkane by adding NaN 3 in DMSO at 100 °C to give 20 – 25 in good yields . These azidoalkane compounds were hydrogenated by use of LiAlH 4 (or C/Pd for 22 and 25 ) to create 26 – 30 and 46 (Scheme ) …”

Section: Chemistrymentioning

confidence: 99%

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Design, Synthesis, and Structure–Activity Relationship Studies of Novel 3-Alkylindole Derivatives as Selective and Highly Potent Myeloperoxidase Inhibitors

Soubhye

Aldib²,

Elfving

et al. 2013

J. Med. Chem.

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Due to its production of potent antimicrobial oxidants including hypochlorous acid, human myeloperoxidase (MPO) plays a critical role in innate immunity and inflammatory diseases. Thus MPO is an attractive target in drug design. (Aminoalkyl)fluoroindole derivatives were detected to be very potent MPO inhibitors; however, they also promote inhibition of the serotonin reuptake transporter (SERT) at the same concentration range. Via structure-based drug design, a new series of MPO inhibitors derived from 3-alkylindole were synthesized and their effects were assessed on MPO-mediated taurine chlorination and low-density lipoprotein oxidation as well as on inhibition of SERT. The fluoroindole compound with three carbons in the side chain and one amide group exhibited a selectivity index of 35 (Ki/IC50) with high inhibition of MPO activity (IC50 = 18 nM), whereas its effect on SERT was in the micromolar range. Structure-function relationships, mechanism of action, and safety of the molecule are discussed.

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Synthesis of 1,2-Diamino-1-phenylpropane Diastereoisomers from u-N-Trifluoroacetyl-2-amino-1-phenylpropan-1-ol

Cited by 5 publications

References 17 publications

Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors

Structure-Based Design, Synthesis, and Pharmacological Evaluation of 3-(Aminoalkyl)-5-fluoroindoles as Myeloperoxidase Inhibitors

Formation of Trifluoroacetylated Ephedrine During the Analysis of a Pseudoephedrine‐Formaldehyde Adduct by TFAA Derivatization Followed by GC‐MS

Design, Synthesis, and Structure–Activity Relationship Studies of Novel 3-Alkylindole Derivatives as Selective and Highly Potent Myeloperoxidase Inhibitors

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