title: Stereoselective and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol.
abstract: [reaction: see text] Two short and efficient synthesis routes have been developed for bis-THF-alcohol 2, a key building block of the investigational HIV protease inhibitor TMC114 (1). Using S-2,3-O-isopropylideneglyceraldehyde (4) as the source of chirality, both routes are based on a diastereoselective Michael addition of nitromethane to give predominantly the syn congeners 6 followed by a Nef oxidation and cyclization to afford lactone acetals 8, which are reduced and cyclized to give 2.
authors.affiliation: DSM Pharma Chemicals, LS-ASC&D, PO Box 18, 6160 MD Geleen, The Netherlands. peter.quaedflieg@dsm.com
authors.forename: Peter J L M
authors.initials: PJ
authors.lastname: Quaedflieg
authors.forename: Bart R R
authors.initials: BR
authors.lastname: Kesteleyn
authors.forename: Piet B T P
authors.initials: PB
authors.lastname: Wigerinck
authors.forename: Nicolaas M F
authors.initials: NM
authors.lastname: Goyvaerts
authors.forename: Robert Jan
authors.initials: RJ
authors.lastname: Vijn
authors.forename: Constantinus S M
authors.initials: CS
authors.lastname: Liebregts
authors.forename: Jaap H M H
authors.initials: JH
authors.lastname: Kooistra
authors.forename: Claudia
authors.initials: C
authors.lastname: Cusan
mesh_terms: D003500:Cyclization; D000069454:Darunavir; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C513052:hexahydrofuro(2,3-b)furan-3-ol; D000069454:Darunavir