title: Stereoselective synthesis of an anti-HIV drug candidate.
abstract: The asymmetric synthesis of a Merck anti-HIV drug candidate is described. The target molecule contains four stereogenic centers, three of which are located in a highly functionalized cyclopentane unit. The convergent synthesis involves the preparation of two key advanced intermediates: the cyclopentane unit and a substituted pyrazole unit. The cyclopentane unit was prepared via two different procedures; a highly diastereoselective Diels-Alder reaction with a chiral oxazolidinone auxiliary and a sequence that incorporated a molybdenum-catalyzed asymmetric allylic alkylation reaction to set the stereocenters. The other key step was a highly diastereoselective hydroxyl-directed reductive amination. The overall yield for the 16-step synthesis was 10%.
authors.affiliation: Department of Process Research, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. dave_conlon@merck.com
authors.forename: David A
authors.initials: DA
authors.lastname: Conlon
authors.forename: Mark S
authors.initials: MS
authors.lastname: Jensen
authors.forename: Michael
authors.initials: M
authors.lastname: Palucki
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Yasuda
authors.forename: Joann M
authors.initials: JM
authors.lastname: Um
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yang
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Hartner
authors.forename: Fuh-Rong
authors.initials: FR
authors.lastname: Tsay
authors.forename: Yi
authors.initials: Y
authors.lastname: Hsiao
authors.forename: Philip
authors.initials: P
authors.lastname: Pye
authors.forename: Nelo R
authors.initials: NR
authors.lastname: Rivera
authors.forename: David L
authors.initials: DL
authors.lastname: Hughes