title: Formal total synthesis of aliskiren.
abstract: The efficient and selective formal total synthesis of aliskiren is described. Aliskiren, a renin inhibitor drug, has received considerable attention, primarily because it is the first of the renin inhibitor drugs to be approved by the FDA. Herein, the formal synthesis of aliskiren by iridium-catalyzed asymmetric hydrogenation of two allylic alcohol fragments is reported. Screening a number of N,P-ligated iridium catalysts yielded two catalysts that gave the highest enantioselectivity in the hydrogenation, which gave the saturated alcohols in 97 and 93 % ee. In only four steps after hydrogenation, the fragments were combined by using the Julia-Kocienski reaction to produce late-stage intermediate in an overall yield of 18 %.
authors.affiliation: Department of Organisk Kemi, Stockholm Universitet, Arrehniuslaboratoriet, 10691 Stockholm (Sweden).
authors.forename: Byron K
authors.initials: BK
authors.lastname: Peters
authors.forename: Jianguo
authors.initials: J
authors.lastname: Liu
authors.forename: Cristiana
authors.initials: C
authors.lastname: Margarita
authors.forename: Pher G
authors.initials: PG
authors.lastname: Andersson
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D005650:Fumarates / Q000138:chemical synthesis* / Q000737:chemistry; D006865:Hydrogenation; D007495:Iridium / Q000737:chemistry*; D020005:Propanols / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D007495:Iridium; D020005:Propanols; D000092502:Renin Inhibitors; C006463:allyl alcohol; C446481:aliskiren
keywords: asymmetric synthesis; hydrogenation; iridium; olefination; total synthesis