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 %.
Formal total synthesis of aliskiren / Peters, B. K.; Liu, J.; Margarita, C.; Andersson, P. G.. - In: CHEMISTRY. - ISSN 1521-3765. - 21:19(2015), pp. 7292-7296. [10.1002/chem.201406523]
Formal total synthesis of aliskiren
Margarita, C.;
2015
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 %.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
