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Formal Total Synthesis of Aliskiren
Author(s) -
Peters Byron K.,
Liu Jianguo,
Margarita Cristiana,
Andersson Pher G.
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201406523
Subject(s) - aliskiren , iridium , renin inhibitor , catalysis , chemistry , alcohol , combinatorial chemistry , yield (engineering) , asymmetric hydrogenation , total synthesis , renin–angiotensin system , enantioselective synthesis , stereochemistry , organic chemistry , medicine , materials science , blood pressure , metallurgy
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 %.