title: Development of an asymmetric synthesis of a chiral quaternary FLAP inhibitor.
abstract: A practical sequence involving a noncryogenic stereospecific boronate rearrangement followed by a robust formylation with an in situ generated DCM anion has been developed for the asymmetric construction of an all-carbon quaternary stereogenic center of a FLAP inhibitor. The key boronate rearrangement was rendered noncryogenic and robust by using LDA as the base and instituting an in situ trapping of the unstable lithiated benzylic carbamate with the boronic ester. A similar strategy was implemented for the DCM formylation reaction. It was found that the 1,2-boronate rearrangement for the formylation reaction could be temperature-controlled, thus preventing overaddition of the DCM anion and rendering the process reproducible. The robust stereospecific boronate rearrangement and formylation were utilized for the practical asymmetric synthesis of a chiral quaternary FLAP inhibitor.
authors.affiliation: Department of Chemical Development, Boehringer-Ingelheim Pharmaceuticals Inc. , 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fandrick
authors.forename: Jason A
authors.initials: JA
authors.lastname: Mulder
authors.forename: Nitinchandra D
authors.initials: ND
authors.lastname: Patel
authors.forename: Joe
authors.initials: J
authors.lastname: Gao
authors.forename: Michael
authors.initials: M
authors.lastname: Konrad
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Archer
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Buono
authors.forename: Adil
authors.initials: A
authors.lastname: Duran
authors.forename: Rolf
authors.initials: R
authors.lastname: Schmid
authors.forename: Juergen
authors.initials: J
authors.lastname: Daeubler
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Desrosiers
authors.forename: Xingzhong
authors.initials: X
authors.lastname: Zeng
authors.forename: Sonia
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Shengli
authors.initials: S
authors.lastname: Ma
authors.forename: Bo
authors.initials: B
authors.lastname: Qu
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Li
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Fandrick
authors.forename: Nelu
authors.initials: N
authors.lastname: Grinberg
authors.forename: Heewon
authors.initials: H
authors.lastname: Lee
authors.forename: Todd
authors.initials: T
authors.lastname: Bosanac
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Chen
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bartolozzi
authors.forename: Peter
authors.initials: P
authors.lastname: Nemoto
authors.forename: Carl A
authors.initials: CA
authors.lastname: Busacca
authors.forename: Jinhua J
authors.initials: JJ
authors.lastname: Song
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Yee
authors.forename: Paige E
authors.initials: PE
authors.lastname: Mahaney
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake
mesh_terms: D058946:5-Lipoxygenase-Activating Protein Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D001896:Boron Compounds / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry*; D002384:Catalysis; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D058946:5-Lipoxygenase-Activating Protein Inhibitors; D001896:Boron Compounds; D002219:Carbamates