441794-87-2Relevant academic research and scientific papers
Conception and evolution of stereocontrolled strategies toward functionalized 8-aryloctanoic acids related to the total synthesis of aliskiren
Hanessian, Stephen,Chnard, Etienne,Guesn, Sbastien,Cusson, Jean-Philippe
, p. 9531 - 9545 (2015/02/19)
A detailed account is given describing the approaches used toward the total synthesis of aliskiren. In particular, ring-closing metathesis with the Hoveyda-Grubbs catalyst accelerates the formation of a 9-membered lactone from an (R)-ester. The diastereom
Total synthesis of "Aliskiren": The first renin inhibitor in clinical practice for hypertension
Hanessian, Stephen,Guesne, Sebastien,Chenard, Etienne
supporting information; experimental part, p. 1816 - 1819 (2010/09/16)
We report a "macrocycle route" toward aliskiren, a drug presently marketed for the treatment of hypertension, using a highly stereocontrolled approach starting from a common "isopropyl chiron". Highlights of the synthesis include a challenging RCM reaction to produce a nine-membered unsaturated lactone, a highly stereoselective catalytic Du Bois aziridination, and a regio- and diastereoselective aziridine ring-opening to a vicinal amino alcohol.
The power of visual imagery in synthesis planning. Stereocontrolled approaches to CGP-60536B, a potent renin inhibitor
Hanessian, Stephen,Claridge, Stephen,Johnstone, Shawn
, p. 4261 - 4274 (2007/10/03)
Two strategies were developed toward the stereocontrolled synthesis of 8-aryl-3-hydroxy-4-amino-2,7-diisopropyloctanoic acids with predetermined stereogenic centers. This is a generic motif in a new class of potent inhibitors of the enzyme renin, exemplified by CGP-60536B. The synthesis relies on the utilization of L-pyroglutamic acid as chiron, and proceeds through the incorporation of required functionality by exploiting internal induction. One of the strategies shows the power of visual imagery in synthesis planning, akin to a Dali-like representation of objects that can be viewed in more than one way. Thus, the entire carbon skeleton of the target molecule is encompassed in a partially functionalized bicyclic indolizidinone precursor. In a second strategy, an intermediate common to the first approach is elaborated into an appended -lactone which is alkylated through enolate chemistry and ultimately transformed into the intended target compound. X-ray crystallography was used to corroborate the structures and stereochemistries of several intermediates.
