492-41-1

Usage

Uses

Used in Pharmaceutical Industry:
L-(-)-Ephedrine is used as a starting material for the synthesis of various pharmaceutical compounds, including ephedrine, pseudoephedrine, and methamphetamine. It is utilized in the production of decongestants, bronchodilators, and stimulants due to its sympathomimetic effects.
Used in Metabolite Research:
L-(-)-Ephedrine serves as a metabolite of Phenmetrazine, which is relevant for research purposes in understanding the metabolic pathways and effects of Phenmetrazine.
Used in Chemical Synthesis:
The alkaloid is also used in the chemical synthesis of various compounds due to its unique chemical properties, such as its white powder form and specific optical rotation values for its salts and derivatives.

Safety Profile

A human poison by ingestion. Poison experimentally by intravenous, subcutaneous, and intraperitoneal routes. Moderately toxic by an unspecified route. Human systemic effects by ingestion: sleep, increased pulse rate without blood pressure decrease, and chronic pulmonary edema or congestion, convulsions, headache, and blood pressure elevation. Used in production of drugs of abuse. When heated to decomposition it emits toxic fumes of NOx.

References

Kanao., Ber., 63,95 (1930) Wolfes., Arch. Pharrn., 268,87 (1930) Hey., J. Chern. Soc., 1232 (1930) Akabori, Momotani., J. Chern. Soc., Japan, 64, 608 (1943) Hoover, Hass., J. Org. Chern., 12,506 (1947)

InChI:InChI=1/C9H13NO/c1-7(10)9(11)8-5-3-2-4-6-8/h2-7,9,11H,10H2,1H3/t7-,9-/m0/s1

Upstream product

• 14838-15-4 u-2-amino-1-phenylpropan-1-ol 
• 1798-60-3 (R)-1-hydroxy-1-phenyl-2-propanone 
• 55253-39-9 (R)-1-hydroxy-1-phenylpropan-2-one oxime 
• 104-53-0 3-phenyl-propionaldehyde 
• 93643-58-4 (4S,5R)-2,4-Dimethyl-2,5-diphenyl-oxazolidine 
• 123367-08-8 (S)-1-Phenyl-2-pyrrol-1-yl-propan-1-ol 
• 154-41-6 erythro-1-phenyl-1-hydroxy-2-propylammonium chloride 
• 630-19-3 pivalaldehyde 
• 123-72-8 butyraldehyde 
• 20993-63-9 ((S)-2-Hydroxy-1-methyl-2-phenyl-ethyl)-carbamic acid ethyl ester 
• 141900-27-8 (1R,2S)-2-Hydroxyamino-1-phenyl-propan-1-ol 
• 2043-61-0 cyclohexanecarbaldehyde 
• 113322-99-9 tert-butyl ((1R,2S)-1-hydroxy-1-phenylpropan-2-yl)carbamate 
• 196409-10-6 (-)-(R)-1-hydroxy-1-phenyl-2-propanone 2-(O-methyloxime) 

Downstream Products

• 299-42-3 ephedrine 
• 117465-77-7 L-erythro-2-amino-1-(4-nitro-phenyl)-propanol-⁽¹⁾ 
• 61347-76-0 NH-benzyl-(1R,2S)-norephedrine 
• 126524-08-1 4-nitro-benzoic acid-((1S,2R)-2-hydroxy-1-methyl-2-phenyl-ethylamide); N-(4-nitro-benzoyl)-(-)-norephedrine 
• 477807-90-2 phenylacetic acid-((1S,2R)-2-hydroxy-1-methyl-2-phenyl-ethylamide) 
• 64868-20-8 (1S,2R)-(1-methyl-2-phenyl-2-hydroxy)ethyltrimethylammonium iodide 
• 83780-49-8 (4S)-cis-4-methyl-5-phenyl-oxazolidine 
• 58635-91-9 (4R)-2-ethyl-4r-methyl-5c-phenyl-4,5-dihydro-oxazole 
• 56571-91-6 (1R,2S)-1-phenyl-2-(1-pyrrolidinyl)-1-propanol 
• 108915-10-2 (4S,5R)-(+)-4-Methyl-5-phenyl-2-(2-pyridinyl)-2-oxazolin 
• 115651-77-9 (1R,2S)-(+)-2-(N,N-di-n-butylamino)-1-phenylpropan-1-ol 
• 150125-70-5 (2S,4S,5R)-2-<(R)-α-<(tert-butyldimethylsilyl)oxy>benzyl>-2,4-dimethyl-5-phenyloxazolidine 
• 133576-76-8 (1R,2S)-1-phenyl-2-piperidinopropanol 
• 77387-33-8 (1R,2S)-(-)-N-formylnorephedrine 

Relevant academic research and scientific papers

High Regio- and Stereoselective Multi-enzymatic Synthesis of All Phenylpropanolamine Stereoisomers from β-Methylstyrene

We present a one-pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5 %) and analytical yields (up to 95 %) by using 1-phenylpropane-1,2-diols as key intermediates. This bioamination entails the combination of an alcohol dehydrogenase (ADH), an ω-transaminase (ωTA) and an alanine dehydrogenase to create a redox-neutral network, which harnesses the exquisite and complementary regio- and stereo-selectivities of the selected ADHs and ωTAs. The requisite 1-phenylpropane-1,2-diol intermediates were obtained from trans- or cis-β-methylstyrene by combining a styrene monooxygenase with epoxide hydrolases. Furthermore, in selected cases, the envisioned cascade enabled to obtain the structural isomer (1S,2R)-1-amino-1-phenylpropan-2-ol in high optical purity (er and dr >99.5 %). This is the first report on an enzymatic method that enables to obtain all of the four possible PPA stereoisomers in great enantio- and diastereo-selectivity.

Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase

A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.

Selective Nonsteroidal Glucocorticoid Receptor Modulators for the Inhaled Treatment of Pulmonary Diseases

A class of potent, nonsteroidal, selective indazole ether-based glucocorticoid receptor modulators (SGRMs) was developed for the inhaled treatment of respiratory diseases. Starting from an orally available compound with demonstrated anti-inflammatory activity in rat, a soft-drug strategy was implemented to ensure rapid elimination of drug candidates to minimize systemic GR activation. The first clinical candidate 1b (AZD5423) displayed a potent inhibition of lung edema in a rat model of allergic airway inflammation following dry powder inhalation combined with a moderate systemic GR-effect, assessed as thymic involution. Further optimization of inhaled drug properties provided a second, equally potent, candidate, 15m (AZD7594), that demonstrated an improved therapeutic ratio over the benchmark inhaled corticosteroid 3 (fluticasone propionate) and prolonged the inhibition of lung edema, indicating potential for once-daily treatment.

Stereoselective Catalytic Synthesis of Active Pharmaceutical Ingredients in Homemade 3D-Printed Mesoreactors

3D-printed flow reactors were designed, fabricated from different materials (PLA, HIPS, nylon), and used for a catalytic stereoselective Henry reaction. The use of readily prepared and tunable 3D-printed reactors enabled the rapid screening of devices with different sizes, shapes, and channel dimensions, aimed at the identification of the best-performing reactor setup. The optimized process afforded the products in high yields, moderate diastereoselectivity, and up to 90 % ee. The method was applied to the continuous-flow synthesis of biologically active chiral 1,2-amino alcohols (norephedrine, metaraminol, and methoxamine) through a two-step sequence combining the nitroaldol reaction with a hydrogenation. To highlight potential industrial applications of this method, a multistep continuous synthesis of norephedrine has been realized. The product was isolated without any intermediate purifications or solvent switches.

Method for preparing norephedrine and norpseudoephedrine

The invention relates to a method for preparing (1R, 2S)-norephedrine, (1R, 2R)-norpseudoephedrine and a midbody thereof. The method comprises the following steps: in the reaction process in the first step, by taking a carrot as a medium, carrying out bio-transforming on 2-oximido-1-phenylacetone and reducing into (R)-2-oximido-1-phenyl propyl alcohol; in the second step, reducing (R)-2-oximido-1-phenyl propyl alcohol into a mixture of (1R, 2S)-norephedrine and (1R, 2R)-norpseudoephedrine; adding a chiral reliquid reagent (R)-O-acetyl mandelic acid and decomposing, thereby acquiring an optical pure (1R, 2S)-norephedrine and (1R, 2R)-norpseudoephedrine monomeric compound.

A short enantioselective synthesis of ephedrine, amphetamine and their analogues via two stereocentered Co(III)-catalyzed hydrolytic kinetic resolution of racemic syn-benzyloxy epoxide

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.

Efficient 2-step biocatalytic strategies for the synthesis of all nor(pseudo)ephedrine isomers

Chiral 1,2-amino alcohols are important building blocks for chemistry and pharmacy. Here, we developed two different biocatalytic 2-step cascades for the synthesis of all four nor(pseudo)ephedrine (N(P)E) stereoisomers. In the first one, the combination of an (R)-selective thiamine diphosphate (ThDP)-dependent carboligase with an (S)- or (R)-selective ω-transaminase resulted in the formation of (1R,2S)-NE or (1R,2R)-NPE in excellent optical purities (ee >99% and de >98%). For the synthesis of (1R,2R)-NPE, space-time yields up to ～26 g L-1 d-1 have been achieved. Since a highly (S)-selective carboligase is currently not available for this reaction, another strategy was followed to complement the nor(pseudo)ephedrine platform. Here, the combination of an (S)-selective transaminase with an (S)-selective alcohol dehydrogenase yielded (1S,2S)-NPE with an ee >98% and a de >99%. Although lyophilized whole cells are cheap to prepare and were shown to be appropriate for use as biocatalysts, higher optical purities were observed with purified enzymes. These synthetic enzyme cascade reactions render the N(P)E-products accessible from inexpensive, achiral starting materials in only two reaction steps and without the isolation of the reaction intermediates. This journal is the Partner Organisations 2014.

Two steps in one pot: Enzyme cascade for the synthesis of nor(pseudo)ephedrine from inexpensive starting materials

Two steps in one pot: An enzyme cascade consisting of a lyase and an (R)- or (S)-selective ω-transaminase (TA) provides (1R,2R)-norpseudoephedrine and (1R,2S)-norephedrine in only two steps. The intermediate is not isolated in this one-pot reaction and the products are obtained in high enantio- and diastereomeric purity. Moreover, the by-product from the second reaction can be recycled to serve as the substrate for the first reaction. Copyright

Stereoselective synthesis of norephedrine and norpseudoephedrine by using asymmetric transfer hydrogenation accompanied by dynamic kinetic resolution

Each of the enantiomers of both norephedrine and norpseudoephedrine were stereoselectively prepared from the common, prochiral cyclic sulfamidate imine of racemic 1-hydroxy-1-phenyl-propan-2-one by employing asymmetric transfer hydrogenation (ATH) catalyzed by the well-defined chiral Rh-complexes, (S,S)- or (R,R)-Cp*RhCl(TsDPEN), and HCO2H/Et3N as the hydrogen source. The ATH processes are carried out under mild conditions (rt, 15 min) and are accompanied by dynamic kinetic resolution.

Charge-transfer interactions: An efficient tool for recycling bis(oxazoline)-copper complexes in asymmetric henry reactions

An anthracenyl-modified chiral bis(oxazoline) copper complex has been demonstrated to efficiently promote nitroaldol reactions between structurally varying aldehydes and nitromethane or nitroethane. The catalyst was recovered through formation of a charge transfer complex between the chiral ligand and trinitrofluorenone and its subsequent precipitation with pentane. The efficiency of this procedure was proved through several consecutive catalytic cycles that allowed the sturdy formation of the expected product with a high enantioselectivity. The catalyst′s stability was also put to the test in an original multi-substrate procedure. Following the same recovery concept, a new heterogeneous procedure was tested for which trinitrofluorenone was covalently linked to a silica support. Asymmetric heterogeneous catalysis was performed under these conditions as one of the few examples demonstrating the potential catalyst recycling in nitroaldol reactions through reversible, non-covalent interactions. Copyright