20133-93-1Relevant academic research and scientific papers
Reinvestigation of a Catalytic, Enantioselective Alkene Dibromination and Chlorohydroxylation
Denmark, Scott E.,Carson, Nessa
, p. 5728 - 5731 (2015)
Attempts to reproduce eight, putative, enantioselective dibromination and chlorohydroxylation reactions from oft-cited literature studies are described. The reactions were performed with full fidelity to the original report wherever possible. Analysis of the enantiomeric composition was performed by chiral stationary phase HPLC or SFC (CSP-HPLC or CSP-SFC), as opposed to the original report, which used chiral shift reagent NMR spectroscopy. After careful study, the reported levels of enantioselectivity were found to be incorrect. Possible explanations for the false positive results are discussed.
Kinetic resolution of 1-chloro-3-(1-naphthyloxy)-2-propanol, an intermediate in the synthesis of β-adrenergic receptor blockers
Kapoor,Anand,Koul,Chimni,Manhas,Raina,Parshad,Taneja,Qazi
, p. 259 - 269 (2003)
(R)- and (S)-1-chloro-3-(1-naphthyloxy)-2-propanol are intermediates in the synthesis of β-adrenergic blocking agents and antihypertensive drugs such as propranolol and nadoxolol. Herein, improvement in the preparation of racemic 1-chloro-3-(1-naphthyloxy)-2-propanol generated from 1-naphthol and epichlorohydrin are reported. In addition, kinetic resolution studies have been conducted to obtain both (R) and (S)-1-chloro-3-(1-naphthyloxy)-2-propanol. These compounds were obtained in highly optically pure form by the stereoselective hydrolysis of its acyl derivatives using whole cell preparations containing enzymes from native sources. The results were compared with those obtained using commercial lipases.
Facile Synthesis of Propranolol and Novel Derivatives
Bach, Long Giang,Le, Van Thuan,Nguyen, Tan Tai,Nguyen, Thi Anh Nga,Nguyen, Thi Thuong,Nguyen, Trinh Duy,Tran, Nguyen Hai Tai,Tran, Vy Anh,Vo, The Ky,Vo, Thu-Thao Thi
, (2020/10/02)
Propranolol is one of the first medications of the beta-blocker used for antihypertensive drugs. This study reports the facile route for the synthesis of propranolol and its novel derivatives. Herein, propranolol synthesis proceeded from 1-naphthol and isopropylamine under mild and less toxic conditions. Novel propranolol derivatives were designed by reactions of propranolol with benzoyl chloride, pyridinium chlorochromate, and n-butyl bromide through esterification, oxidation reduction, and alkylation, respectively. The isolation and purity of compounds were conducted using column chromatography and thin-layer chromatography. Mass spectrometry and 1H-NMR spectroscopy were applied to identify new compounds structure. Propranolol derivatives from 2-chlorobenzoyl chloride (compound 3), 2-fluorobenzoyl chloride (compound 5), and especially acetic anhydride (compound 6) manifested high yields and significantly increased water solubility. Six semisynthetic propranolol derivatives promise to improve antioxidative and biological activities.
Improvement and simplification of synthesis of 3-aryloxy-1,2-epoxypropanes using solvent-free conditions and microwave irradiations. Relation with medium effects and reaction mechanism
Pchelka, Beata K.,Loupy, Andre,Petit, Alain
, p. 10968 - 10979 (2007/10/03)
Some 3-aryloxy-1,2-epoxypropanes, interesting as potential synthons in β-adrenergic receptor antagonists preparation, were obtained in excellent yields (65-96% within 2-17 min) by microwave activation (monomode system) using solid-liquid solvent-free phase transfer catalysis (PTC). The best results for the O-alkylation of some phenols with epichlorohydrin were obtained using TBAB and NaOH/K2CO3 (1:4 mol/mol) as phase transfer catalyst and more acceptable basic system, respectively. These new procedure is compared with classical methods. Significant specific microwave effect (non-purely thermal) was evidenced in all cases. They were discussed in terms of reaction medium and mechanism, taking into account the variations in polarity of the systems.
Chemoenzymatic synthesis of (S) and (R)-propranolol and sotalol employing one-pot lipase resolution protocol
Kamal, Ahmed,Sandbhor, Mahendra,Ali Shaik, Ahmad
, p. 4581 - 4583 (2007/10/03)
Synthesis of both enantiomers of biologically active propranolol and sotalol has been achieved in high optical purity by one-pot reduction of 3 and 7 followed by in situ lipase resolution of the respective chlorohydrins. Pseudomonas cepacia lipase immobilized on ceramic particles (PS-C) provided the chlorohydrin and acetate, which on nucleophilic substitution with isopropyl amine afforded the target amino alcohols in high enantioselectivity under mild reaction conditions.
Preparation of halohydrin β-blocker precursors using yeast-catalysed reduction
Martinez, Fernando,Del Campo, Carmen,Sinisterra,Llama, Emilio F.
, p. 4651 - 4660 (2007/10/03)
The preparation of halohydrin β-blocker precursors using yeast-catalysed reduction of α-haloketones was performed. The influence in the yield and e.e. of several process variables was analysed. The (S)-enantioselectivity observed with Saccharomyces cerevisiae can be changed to (R)-enantioselectivity using methyl vinyl ketone as selective inhibitor (25 mM). Using resting fresh cells better yields and e.e.s are observed than using growing cells. Yarrowia lipolytica 1240 resting cells gave 87% yield of (S)-1-chloro-3(1-naphthyloxy)propan-2-ol (99% e.e.). Pichia mexicana 11105 resting cells gave 85% yield of (R)-1-chloro-3(1-naphthyloxy)propan-2-ol (precursor of propranolol) (95% e.e). The reduction process is applied to other α-haloketones, a lower e.e. being obtained the closer the size of the ketone substituents.
Design, synthesis and evaluation of a chiral propranolol selector
Del Campo,Llama,Sinisterra
, p. 2627 - 2631 (2007/10/03)
Synthesis of enantiomerically pure (S)-(-)-propranolol, the most active of the widely used beta-blockers adrenergics, was achieved using a new chiral stationary phase (CSP) for the separation of a derivative. This simple methodology shows a significant improvement in the separation of the enantiomers of a propranolol derivative over previous methods.
Improved Delivery through Biological Membranes. 26. Design, Synthesis, and Pharmacological Activity of a Novel Chemical Delivery System for β-Adrenegic Blocking Agents
Bodor, Nicholas,ElKoussi, Alaaeldin,Kano, Masanobu,Nakamura, Toshio
, p. 100 - 106 (2007/10/02)
Novel ketoxime analogues of known β-blockers (propranolol, timolol, carteolol) and tested as potential site-specific chemical delivery systems.It was assumed that a hydrolysis-reduction sequence could produce the active β-blockers in the iris-ciliary body.It was found that some of these bioprecursors are remarcable active in reducing intraocular pressure in rabbits.The ketoxime derivative of propranolol is more effective and much less irritant than its parent β-blocker.While the ketoximes also displayed activity on isoprenaline-induced tachycardia after iv administration, they were void of activity when given orally.Propranolol was found for a prolonged time and in significant concentrations in the rabbit's eye following topical administration of its ketoxime precursor; however, the inactive ketoximes apparently were not converted to the corresponding β-blockers in the eye.A correlation was found between the physicochemical properties of the ketoximes and their conversion to the amino alcohol and thus their subsequent activity.The results suggest that at least some of the ketoxime precursors could have a use as antiglaucoma agents without systemic side effects.
