Journal of Medicinal Chemistry p. 55 - 59 (1988)
Update date:2022-07-29
Topics:
Shetty, H. Umesha
Nelson, Wendel L.
Asymmetric synthesis of 3-<4-(1-hydroxy-2-methoxyethyl)phenoxy>-1-(isopropylamino)-2-propanol (2), the benzylic hydroxylation metabolite of metoprolol (1), is described, and the absolute configurations of the diastereomers were assigned.Ketone 3, prepared in a multistep synthesis, was reduced with a complex of (2S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol(9) and borane, yielding 2, with a ratio of 82:18 for the diastereomers.The absolute configurations 1'S,2S and 1'S2R were assigned for the diastereomers formed in excess on the basis of reductions on closely related alkyl phenyl ketones and the circular dichroism spectrum.Derivatization of the 1'-hydroxyl group of oxazolidinone 10 with a chiral Mosher acid chloride and the use of an HPLC procedure to resolve the resulting esters enabled us to determine the metabolic product stereoselectively for 2.In the presence of the rat liver microsomal fraction, the benzylic hydroxylation of 1 was highly product stereoselective favoring 1'R stereochemistry at the new asymmetric center in racemic 1 and in both enantiomers of 1.Determination of the stereochemistry of 2 will facilitate study of this polymorphically controlled metabolic process.
View MoreAstaTech ( Chengdu) BioPharmaceutical Corp.
website:http://www.astabiochem.cn/
Contact:+86-15198215156-15198215156
Address:SICHUAN CHENGDU
Sichuan Mianzhu Ronghong Chemical Co.,LTd
Contact:8613981840544
Address:XINSHI INDUSTRY PARK,MIANZHU,SICHUAN,CHINA
Contact:+86-021-6989-5597
Address:No.80 Yichuan Rd., Putuo District,Shanghai,P.R.China
Contact:+86-20-32051076
Address:1105,Building A, International Business Incubator,Science City
Linyi Shengxin Pharmaceutical R&D Co., Ltd
Contact:+86-18653953873
Address:West First of Yufeng Road, Yishui County
Doi:10.1002/chem.200801414
(2008)Doi:10.1016/j.jorganchem.2008.10.007
(2009)Doi:10.1021/jm401090a
(2013)Doi:10.1021/jm00338a020
(1963)Doi:10.1039/b9nj00399a
(2010)Doi:10.1016/j.ica.2011.05.008
(2011)