Organocatalytic enantioselective synthesis of β-blockers: (S)-propranolol and (S)-naftopidil

Asymmetric Organocatalytic Efficiency of Synthesized Chiral β-Amino Alcohols in Ring-Opening of Glycidol with Phenols

“…The low regioselectivities obtained in the case of compounds 8 and 10 arising from more electrophilic character of benzylic carbon of styrene oxide when compared with other epoxides. It was shown that amines 2 and 6 exhibited a preference for nucleophilic attack at terminal or achiral carbon of epoxides as a S N 2 reaction to give corresponding chiral b-amino alcohols with retention of configuration on stereogenic center as reported previously [37,38]. Therefore, this method provided an easy and efficient route to the corresponding chiral b-amino alcohols without using any catalyst and excess amounts of amine dealing with thermally sensitive epoxides due to the side reactions.…”

“…The regioselective ring opening of epoxides by amines is an important way for the preparation of b-amino alcohols [37,38]. Thus, chiral b-amino alcohols were synthesized in the catalyst-free medium by regioselective ring opening of terminal epoxides with chiral amines 2 and 6 by using methanol as a solvent (Schemes 1,2).…”

Recent Advances on the Organocatalyzed Enantioselective α-heterofunctionalization of Carbonyl Compounds

“…For instance, (S,S)-ethambutol (23) [26], (R)-selegiline (24) [27] and (-)-anisomycin (27) [30], which could be alternatively synthesized by means of an organocatalyzed α-amination reaction (see section 2.2, Figure 2), could be prepared with similar results by using this transformation. In a similar way, the antiinflammatory halipeptin A (111) [94], the antitumor agents tarchonanthuslactone (112) [95], (+)-cytotrienin A [96] and (+)-harzialactone A and (R)-(+)-4-hexanolide [97], the antibacterials linezolid (113) and eperezolid [98], the antiepileptic drugs levetiracetam (114) [99], the pheromones (-)-endo-brevicomin (115) [100], (+)-disparlure [101] and (2S,3S)-2-hydrohyhexylcyclopentanone [102], and the enzyme inhibitors (+)-panephenanthrin (116) [103], and the β-adrenergic blockers (S)-propranolol (117) and (S)-naftopidil [104] have been synthesized using in all cases the α-aminoxylation of aldehydes as a key step (Figure 12). …”

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as α 1D -adrenoceptor antagonists

“…Individual NAF enantiomers could be obtained by enantioselective synthesis7, 8 and hydrolytic kinetic resolution 9 , but their crystal structures had not been reported so far. We herein described the crystallographic structures of (+)/(–)-NAF and determined their absolute configurations based on single-crystal X-ray diffraction analysis.…”