Key result
A new convergent synthesis strategy utilizing a catalytic stereoselective nitroaldol reaction successfully produced the enantiopure renin inhibitor aliskiren.
Describes a novel stereoselective catalytic nitroaldol reaction strategy for the synthesis of the direct renin inhibitor aliskiren.
New route to aliskiren extends stereoselective synthesis options; leaves open scalability for clinical supply.
Aliskiren is the first‐in‐class orally active direct renin inhibitor. It was approved in 2007 for the treatment of hypertension. We have designed a new strategy for the convergent synthesis of aliskiren that involves a catalytic stereoselective nitroaldol reaction as the key step. A new enantiopure nitroalkane (synthon A1), prepared in only three steps from a commercially available enantiopure 2‐(arylmethyl)‐3‐methyl butanol derivative, was successfully used in a copper‐catalysed Henry reaction to give a nitrolactone intermediate in which the correct configuration for the final product was established at all four stereocentres. Nitro‐group reduction, Boc‐protection of the resulting amine, aminolysis of the lactone with 3‐amino‐2,2‐dimethylpropionamide, and finally Boc‐deprotection led to the enantiopure renin inhibitor aliskiren.
No takes yet. Share an insight, caveat, or question.
Rossi et al. (2015) studied this question. Stereoselective catalytic nitroaldol reaction was evaluated on Synthesis of enantiopure renin inhibitor aliskiren. A new convergent synthesis strategy utilizing a catalytic stereoselective nitroaldol reaction successfully produced the enantiopure renin inhibitor aliskiren.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: