The development of a complementary pathway for the synthesis of aliskiren

	The development of a complementary pathway for the synthesis of aliskiren
	Li,Le-Le; Ding,Jin-Ying; Gao,Lian-Xun; Han,Fu-She
刊名	organic & biomolecular chemistry
	2015
卷号	13 期号:4 页码:1133-1140
关键词	RENIN INHIBITOR ALISKIREN ORALLY-ACTIVE INHIBITORS OLEFIN CROSS-METATHESIS CONVERGENT SYNTHESIS RUTHENIUM CATALYSTS OXIDATIVE CLEAVAGE POTENT CONVERSION ALCOHOLS KETONES
通讯作者	han,fs
英文摘要	the synthesis of aliskiren (1), a recently marketed drug for the treatment of hypertension, is presented. the focus of our synthetic effort is to develop an efficient pathway for the synthesis of (2s,7r,e)-2-isopropyl-7-(4-methoxy-3-(3-methoxypropoxy) benzyl)-n,n, 8-trimethylnon-4-enamide (2a), which has been used as the advanced intermediate toward aliskiren. after an extensive investigation of three different strategies designed to construct the e-olefin functionality in 2a by employing the olefin cross-metathesis, horner-wadsworth-emmons (hwe), and julia-type olefinations, we have established a new protocol for the synthesis of 2a with a substantially improved overall efficiency in terms of the yield (ca. 33%), and diastereo- and e/z-selectivity. the key transformations were the evans chiral auxiliary-aided asymmetric allylation for the synthesis of the appropriate chiral intermediates in excellent enantiomeric purity of higher than 97% ee and a modified julia-kocienski olefination for the highly selective construction of e-2a with up to 13.6 : 1 e/z ratio from the chiral intermediates. consequently, the results provide an appealing option for the synthesis of aliskiren.
收录类别	SCI
语种	英语
公开日期	2016-05-31
内容类型	期刊论文
源URL	[http://ir.ciac.jl.cn/handle/322003/67900]
专题	长春应用化学研究所_长春应用化学研究所知识产出_期刊论文
推荐引用方式 GB/T 7714	Li,Le-Le,Ding,Jin-Ying,Gao,Lian-Xun,et al. The development of a complementary pathway for the synthesis of aliskiren[J]. organic & biomolecular chemistry,2015,13(4):1133-1140.
APA	Li,Le-Le,Ding,Jin-Ying,Gao,Lian-Xun,&Han,Fu-She.(2015).The development of a complementary pathway for the synthesis of aliskiren.organic & biomolecular chemistry,13(4),1133-1140.
MLA	Li,Le-Le,et al."The development of a complementary pathway for the synthesis of aliskiren".organic & biomolecular chemistry 13.4(2015):1133-1140.