title: Enantioselective, biocatalytic reduction of 3-substituted cyclopentenones: application to the asymmetric synthesis of an hNK-1 receptor antagonist.
abstract: A convergent and enantioselective route to the hNK-1 receptor antagonist (1) is described, which sets all six stereogenic centers with high diastereoselectivity and delivers 1 in only 11 steps and 23% overall yield. The process was enabled by the development of the enantioselective enzymatic reduction of 3-functionalized cyclopentenones and stereospecific Pd-catalyzed etherification coupling of fragments 6 and 7.
authors.affiliation: Department of Process Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA. kevin_campos@merck.com
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Campos
authors.forename: Artis
authors.initials: A
authors.lastname: Klapars
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kohmura
authors.forename: David
authors.initials: D
authors.lastname: Pollard
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kato
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takezawa
authors.forename: Jacob H
authors.initials: JH
authors.lastname: Waldman
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Wallace
authors.forename: Cheng-yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Yasuda
mesh_terms: D002384:Catalysis; D003517:Cyclopentanes; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D003517:Cyclopentanes; D006576:Heterocyclic Compounds, 4 or More Rings; D064729:Neurokinin-1 Receptor Antagonists; D010165:Palladium; C013905:cyclopentenone