4199-10-4

Usage

Uses

Used in Pharmaceutical Industry:
(S)-(-)-Propranolol hydrochloride is used as an active enantiomer for its β-adrenergic blocking properties, which contribute to its effectiveness in treating various cardiovascular conditions.
(S)-(-)-Propranolol hydrochloride is used as an antihypertensive agent for managing high blood pressure, as it helps to lower the heart rate and reduce the force of heart contractions.
(S)-(-)-Propranolol hydrochloride is used as an antianginal medication to alleviate chest pain and discomfort caused by angina pectoris, by reducing the oxygen demand of the heart.
(S)-(-)-Propranolol hydrochloride is used as an antiarrhythmic agent (class II) to help regulate abnormal heart rhythms and maintain a normal heartbeat.
(S)-(-)-Propranolol hydrochloride is used as a beta-adrenergic blocking agent, which plays a crucial role in the management of various cardiovascular diseases by controlling the effects of adrenaline on the heart.

Biological Activity

More active enantiomer of the β -adrenoceptor antagonist propranolol ((RS)-1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol hydrochloride ).

Biochem/physiol Actions

(S)-(?)-Propranolol hydrochloride is biologically active enantiomer. It acts as β1 receptor antagonist in thalamocortical neurons. (S)-(?)-Propranolol hydrochloride elicits its inhibitory function on the β1 adrenoceptor in trigeminovascular pain pathway and serves as a preventive medicine in migraine.

Purification Methods

The (+)-salt is the active isomer which blocks isoprenaline tachycardia and is a -adrenergic blocker. [Leclerc et al. Trends Pharmacol Sci 2 18 1981, Howe & Shanks Nature 210 1336 1966.]

InChI:InChI=1/C16H21NO2.ClH/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16;/h3-9,12,14,17-18H,10-11H2,1-2H3;1H/t14-;/m0./s1

Upstream product

• 90-15-3 α-naphthol 
• 115314-14-2 (2s)-(+)-glycidyl 3-nitrobenzenesulfonate 
• 75-31-0 isopropylamine 
• 213130-05-3 (2RS,4R)-4-(1-naphthyloxy)methyl-2-oxo-1,3,2-dioxathiolane 
• 56715-19-6 (S)-3-(1-naphthyloxy)-1,2-propanediol 
• 4199-09-1 (S)-1-isopropylamino-3-(1-naphthyloxy)-2-propanol 
• 318-98-9 Inderal 
• 108433-49-4 1-chloro-2-acetoxy-3-(1-naphthyloxy)propane 
• 20133-93-1 1-chloro-3-(1-naphthoxy)-2-propanol 
• 2461-42-9 3-(1-naphthyloxy)-1,2-epoxypropane 
• 132005-35-7 (S)-(+)-1-chloro-3-(1-naphthyloxy)-2-propanol 
• 119870-22-3 (S)-2-benzyloxy-3-isopropylamino-1-propanol 
• 119870-21-2 ((S)-2-Benzyloxy-3-chloro-propyl)-isopropyl-amine 
• 3019-88-3 sodium naphtholate 

Downstream Products

• 227176-56-9 (R)-2-Phenyl-butyric acid (S)-1-(isopropylamino-methyl)-2-(naphthalen-1-yloxy)-ethyl ester 
• 81907-79-1 (-)-5-Hydroxypropranolol 
• 393828-91-6 (S)-N-desisopropylpropranolol 
• 227176-57-0 (S)-2-Phenyl-butyric acid (R)-1-(isopropylamino-methyl)-2-(naphthalen-1-yloxy)-ethyl ester 
• 227176-55-8 (R)-2-Phenyl-butyric acid (R)-1-(isopropylamino-methyl)-2-(naphthalen-1-yloxy)-ethyl ester 
• 91796-22-4 (+)-5-Hydroxypropranolol 
• 393828-92-7 (R)-N-desisopropylpropranolol 

Relevant academic research and scientific papers

Catalytic Asymmetric Nitroaldol Reaction: An Efficient Synthesis of (S) Propranolol Using the Lanthanum Binaphthol Complex

(S) Propranolol, a more potent optical isomer of the widely used β-blocker, was conveniently synthesized in a highly enantioselective manner by the lanthanum-(R)-(+)-binaphthol complex catalyzed asymmetric nitroaldol reaction.

Covalent Organic Frameworks with Chirality Enriched by Biomolecules for Efficient Chiral Separation

The separation of racemic compounds is important in many fields, such as pharmacology and biology. Taking advantage of the intrinsically strong chiral environment and specific interactions featured by biomolecules, here we contribute a general strategy is developed to enrich chirality into covalent organic frameworks (COFs) by covalently immobilizing a series of biomolecules (amino acids, peptides, enzymes) into achiral COFs. Inheriting the strong chirality and specific interactions from the immobilized biomolecules, the afforded biomolecules?COFs serve as versatile and highly efficient chiral stationary phases towards various racemates in both normal and reverse phase of high-performance liquid chromatography (HPLC). The different interactions between enzyme secondary structure and racemates were revealed by surface-enhanced Raman scattering studies, accounting for the observed chiral separation capacity of enzymes?COFs.

Ultrafast chiral separations for high throughput enantiopurity analysis

Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.

Establishment and Evaluation of the Novel Tetramethylammonium-L-Hydroxyproline Chiral Ionic Liquid Synergistic System Based on Clindamycin Phosphate for Enantioseparation by Capillary Electrophoresis

Much attention has been paid to chiral ionic liquids (ILs) in analytical chemistry, especially its application in capillary electrophoresis (CE) enantioseparation. However, the investigation of chiral ionic liquids synergistic systems based on antibiotic chiral selectors has been reported in only one article. In this work, a novel chiral ionic liquid, tetramethylammonium-L-hydroxyproline (TMA-L-Hyp), was applied for the first time in CE chiral separation to evaluate its potential synergistic effect with clindamycin phosphate (CP) as the chiral selector. As observed, significantly improved separation was obtained in this TMA-L-Hyp/CP synergistic system compared to TMA-L-Hyp or a CP single system. Several primary factors that might influence the separation were investigated, including CP concentration, TMA-L-Hyp concentration, buffer pH, types and concentrations of organic modifier, applied voltage, and capillary temperature. The best results were obtained with a 40 mM borax buffer (pH 7.6) containing 30 mM TMA-L-Hyp, 80 mM CP, and 20% (v/v) methanol, while the applied voltage and temperature were set at 20 kV and 20°C, respectively. Chirality 27:598-604, 2015.

Uridine, thymidine and inosine used as chiral stationary phases in HPLC

In this paper, we present the first enantioseparations research using thymidine, uridine and inosine as chiral stationary phase bonded to silica gel via 3-(triethoxysilyl)propyl isocyanate in HPLC. Thymidine and uridine chiral stationary phases possess enantioseparation selectivity for alcohols, amines, ketones and carboxylic acids to some degree in normal-phase and reversed-phase mode. This work indicates that nucleoside or deoxynucleoside can be useful for the separation of enantiomers in the liquid phase as a new kind of chiral stationary phase.

Combined use of ionic liquid and hydroxypropyl-β-cyclodextrin for the enantioseparation of ten drugs by capillary electrophoresis

In the present study, hydroxypropyl-β-cyclodextrin and an ionic liquid (1-ethyl-3-methylimidazolium-l-lactate) were used as additives in capillary electrophoresis for the enantioseparation of 10 analytes, including ofloxacin, propranolol hydrochloride, dioxopromethazine hydrochloride, isoprenaline hydrochloride, chlorpheniramine maleate, liarozole, tropicamide, amlodipine benzenesulfonate, brompheniramine maleate, and homatropine methylbromide. The effects of ionic liquid concentrations, salt effect, cations, and anions of ionic liquids on enantioseparation were investigated and the results proved that there was a synergistic effect between hydroxypropyl-β-cyclodextrin and the ionic liquid, and the cationic part of the ionic liquid played an important role in the increased resolution. With the developed dual system, all the enantiomers of 10 analytes were well separated in resolutions of 5.35, 1.76, 1.85, 2.48, 2.88, 1.43, 5.45, 4.35, 2.76, and 2.98, respectively. In addition, the proposed method was applied to the determination of the enantiomeric purity of S-ofloxacin after validation of the method in terms of selectivity, repeatability, linearity range, accuracy, precision, limit of detection (LOD), and limit of quality (LOQ). Chirality 25:409-414, 2013.

Organocatalytic enantioselective synthesis of β-blockers: (S)-propranolol and (S)-naftopidil

An efficient enantioselective synthesis of β-adrenergic blockers (S)-propranolol and (S)-naftopidil with >98% ee using an l-proline-catalyzed α-aminoxylation of an aldehyde as a key step is described.

Cyclic sulfites, key intermediates in synthesis of 1-alkylamino-3-aryloxy-2-propanols from glycidol

A number of 3-aryloxypropanedioles were obtained by treating glycidol with phenols. The latter with thionyl chloride afforded 4-aryloxymethyl-1,3,2-dioxathiolane 2-oxides. These compounds were also obtained from 4-chloromethyl-1,3,2-dioxathiolane 2-oxides by substitution aryloxy group for chlorine. The cyclic sulfides synthesized are universal intermediates in the synthesis of chiral aryloxypropanolamines among which are known β-adrenoblockaders, cardiovascular drugs. From (S)-glycidol, (S)-alprenolol, (S)-propanolol, and (S)-thymolol were synthesized.

New approach to nonracemic 1-alkylamino-3-aryloxypropan-2-ols belonging to β-blockers via cyclic sulfites

Nonracemic β-blockers, viz., (S)-propranolol and (S)-timolol, were prepared from (S)-glycidol in three steps consisting in the reaction with SOCl2 followed by the reaction of the resulting (4S)-4-chloromethyl-2-oxo-1,3,2-dioxathiolanes with the corresponding phenol and the final cleavage of (4R)-aryloxymethyl sulfites under the action of amines in DMF.

Process for the preparation of 3-amino-2-hydroxy-1-propyl ethers

PCT No. PCT/JP97/03220 Sec. 371 Date Apr. 28, 1999 Sec. 102(e) Date Apr. 28, 1999 PCT Filed Sep. 12, 1997 PCT Pub. No. WO98/12171 PCT Pub. Date Mar. 26, 1998A process for preparation of 3-amino-2-hydroxy-1-propyl ether of the formula wherein R1 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heterocyclic ring, R2 and R3 are the same or different hydrogen atom, a substituted or unsubstituted alkyl, or may form a ring together with an adjacent nitrogen atom, which ring may be interrupted with nitrogen atom, oxygen atom or sulfur atom, which is characterized in reacting an epoxy compound of the formula wherein X is halogen, in the presence of a fluoride salt, with an alcohol and then reacting an amine. According to the above method, an intermediates for synthesis of medicines is obtained in good yield and highly optical purity.