105780-38-9Relevant articles and documents
Kinetic resolution of (: RS)-1-chloro-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol: a metoprolol intermediate and its validation through homology model of Pseudomonas fluorescens lipase
Soni, Surbhi-,Dwivedee, Bharat P.,Sharma, Vishnu K.,Banerjee, Uttam C.
, p. 36566 - 36574 (2017)
In the present study Pseudomonas fluorescens lipase (PFL) was screened as a time efficient biocatalyst for the kinetic resolution of a racemic intermediate [(RS)-1-chloro-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol] of metoprolol, an important selective β1-blocker drug. PFL selectively acylated the R-form of this racemic intermediate in a short duration of 3 h. Different reaction parameters were optimized to achieve maximum enantioselectivity. It was found that at 30 °C, enzyme activity of 400 units and substrate concentration of 10 mM gave a high enantioselectivity and conversion in an optimum time of 3 hours (C = 50.5%, eep = 97.2%, ees = 95.4%, E = 182). To validate these experimental results, the 3D structure of PFL was built using homology modelling. Validation of the model through Ramachandran plot (92.7% in favored region), Errat plot (overall quality factor, 79.27%), Verify-3D score (86.19) and ProSA-Z score (-6.24) depicted the overall good quality of the model. Molecular docking of the R- and S-enantiomers of the intermediate, which was performed on this model, demonstrated a strong H-bond interaction (1.6 ?) between the hydroxyl group of the R-enantiomer and Arg54, a key binding residue of the catalytic site of PFL, while no significant interaction with the S-enantiomer was observed. Thus, the outcome of this docking study was in agreement with the experimental data, clarifying that PFL preferentially catalysed the transesterification of the R-enantiomer into the corresponding ester, leaving the S-enantiomer intact.
Asymmetric hydrolytic kinetic resolution with recyclable polymeric Co(iii)-salen complexes: A practical strategy in the preparation of (S)-metoprolol, (S)-toliprolol and (S)-alprenolol: Computational rationale for enantioselectivity
Roy, Tamal,Barik, Sunirmal,Kumar, Manish,Kureshy, Rukhsana I.,Ganguly, Bishwajit,Khan, Noor-Ul H.,Abdi, Sayed H. R.,Bajaj, Hari C.
, p. 3899 - 3908 (2015/02/19)
A series of chiral polymeric Co(iii)-salen complexes based on a number of achiral and chiral linkers were synthesized and their catalytic performances were assessed in the asymmetric hydrolytic kinetic resolution of terminal epoxides. The effects of the linker were judiciously studied and it was found that in the case of the chiral BINOL-based polymeric salen complex 1, there was an enrichment in catalyst reactivity and enantioselectivity of the unreacted epoxide, particularly in the case of short as well as long chain aliphatic epoxides. Good isolated yields of the unreacted epoxide (up to 46% compared to 50% theoretical yield) along with high enantioselectivity (up to 99%) were obtained in most cases using catalyst 1. Further studies showed that catalyst 1 could retain its catalytic activity for six cycles under the present reaction conditions without any significant loss in activity or enantioselectivity. To show the practical applicability of the above synthesized catalyst we have synthesised some potent chiral β-blockers in moderate yield and high enantioselectivity using complex 1. The DFT (M06-L/6-31+G??//ONIOM(B3LYP/6-31G?:STO-3G)) calculations revealed that the chiral BINOL linker influences the enantioselectivity achieved with Co(iii)-salen complexes. Further, the transition state calculations show that the R-BINOL linker with the (S,S)-Co(iii)-salen complex is energetically preferred over the corresponding S-BINOL linker with the (S,S)-Co(iii)-salen complex for the HKR of 1,2-epoxyhexane. The role of non-covalent C-H?π interactions and steric effects has been discussed to control the HKR reaction of 1,2-epoxyhexane.
Asymmetric synthesis of (S)-metoprolol via sharpless asymmetric dihydroxylation induced by a recoverable polymer ligand QN-AQNOPEG-OMe
Cheng, Sikun,Liu, Xueying,Wang, Pingan,Li, Xiaoye,He, Wei,Zhang, Shengyong
, p. 516 - 519 (2012/10/30)
The catalytic asymmetric dihydroxylation (AD) discovered by Sharpless, a Nobel Prize winner in 2001, has rapidly become an invaluable synthetic tool in the possibility of converting prochiral olefins to chiral vicinal diols. After our long-running investi
Zinc tetrafluoroborate hydrate as a mild catalyst for epoxide ring opening with amines: Scope and limitations of metal tetrafluoroborates and applications in the synthesis of antihypertensive drugs (RS)/(R)/(S)-metoprolols
Pujala, Brahmam,Rana, Shivani,Chakraborti, Asit K.
experimental part, p. 8768 - 8780 (2011/12/04)
The scope and limitations of metal tetrafluoroborates have been studied for epoxide ring-opening reaction with amines, and Zn(BF4) 2?xH2O has been found to be a mild and efficient catalyst affording high yields under solvent-free conditions at rt with excellent chemo-, regio-, and stereoselectivities. The catalytic efficiency followed the order Zn(BF4)2?xH2O ? Cu(BF4)2?xH2O > Co(BF4) 2?6H2O ? Fe(BF4)2? 6H2O > LiBF4 for reactions with cyclohexene oxide and Zn(BF4)2?xH2O ? Co(BF4) 2?6H2O ? Fe(BF4)2? 6H2O > Cu(BF4)2?xH2O for stilbene oxide, but AgBF4 was ineffective. For reaction of styrene oxide with aniline, the metal tetrafluoroborates exhibited comparable regioselectivity (1:99-7:93) with preferential reaction at the benzylic carbon of the epoxide ring. A reversal of regioselectivity (91:1-69:31) in favor of the reaction at the terminal carbon of the epoxide ring was observed for reaction with morpholine. The regioselectivity was dependent on the electronic and steric factors of the epoxide and the pKa of the amine and independent of amine nucleophilicity. The role of the metal tetrafluoroborates is envisaged as "electrophile nucleophile dual activation" through cooperativity of coordination, charge-charge interaction, and hydrogen-bond formation that rationalizes the catalytic efficiency, substrate reactivity, and regioselectivity. The methodology was used for synthesis of cardiovascular drug metoprolol as racemic and enriched enantiomeric forms.
CARDIOTONIC COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST BETA-ADRENERGIC RECEPTORS AND PHOSPHODIESTERASE
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Page/Page column 80, (2010/11/08)
The present invention provides compounds possessing inhibitory activity against ? adrenergic receptors and phosphodiesterase (PDE), including type 3 phosphodiesterase (PDE-3). The present invention further provides pharmaceutical compositions comprising s
Di-substituted aminomethyl-chroman derivative beta-3 adrenoreceptor agonists
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, (2008/06/13)
This invention is related to novel di-substituted aminomethyl chroman derivatives which are useful in the treatment of beta-3 receptor-mediated conditions.
Enantioselective ring opening of epoxides with trimethylsilyl azide (TMSN3) in the presence of β-cyclodextrin: An efficient route to 1,2-azido alcohols
Kamal, Ahmed,Arifuddin,Rao, Maddamsetty V.
, p. 4261 - 4264 (2007/10/03)
The ring opening of epoxides with nucleophiles such as TMSN3 and isopropylamine takes place enantioselectively in the presence of β- cyclodextrin under extremely mild conditions and the azido alcohols and amino alcohols are formed as (S)-isomers. (C) 1999 Published by Elsevier Science Ltd.
Kinetic resolution of aryl glycidyl ethers : A practical synthesis of optically pure β-blocker - S-metoprolol
Gurjar, Mukund K.,Sadalapure, Kashinath,Adhikari, Susanta,Sarma, Bugga V. N. B. S.,Talukdar, Arindam,Chorghade, Mukund S.
, p. 1471 - 1476 (2007/10/03)
Kinetic resolution of (±)-aryl glycidyl ethers using (R,R)-salen Co(III)OAc and water provided enantiomerically pure arylglycidyl ether and 1-arylglycerol derivatives with high enantiomeric excess. Application of this approach to (S)-metoprolol has been d
