title: Total synthesis of flocoumafen via knoevenagel condensation and intramolecular ring cyclization: general access to natural products.
abstract: The total synthesis and structure determination of cis- and trans-flocoumafen was described. The key synthetic steps involve Knoevenagel condensation with p-methoxybenzaldehyde, in situ decarboxylation and intramolecular ring cyclization to construct the tetralone skeleton. Stereospecific reduction of the O-alkylated ketone 13 afforded good yield of precusor alcohol 5. Final coupling of alcohol 5 with 4-hydroxy-coumarin yielded flocoumafen (1). Separation and structure determination of cis- and trans-flocoumafen through 2D NMR analyses-assisted computer simulation techniques for the evaluation of anticoagulant activities are reported for the first time. This method is useful for generating the core tetralone skeleton of 4-hydroxycoumarin derivatives and provides a generalized access to various warfarin type anticoagulants.
authors.affiliation: Department of Neuroscience and Medical Research Institute, School of Medicine, Ewha Womans University, Seoul 158-710, Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Jung
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lim
authors.forename: Yongnam
authors.initials: Y
authors.lastname: Lee
authors.forename: Dongguk
authors.initials: D
authors.lastname: Min
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ricci
authors.forename: Oe-Sook
authors.initials: OS
authors.lastname: Park
authors.forename: Mankil
authors.initials: M
authors.lastname: Jung
mesh_terms: D015110:4-Hydroxycoumarins / Q000138:chemical synthesis* / Q000737:chemistry*; D000478:Alkylation; D000925:Anticoagulants / Q000737:chemistry; D001547:Benzaldehydes / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry*; D003500:Cyclization; D003653:Decarboxylation
chemical_list: D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D001547:Benzaldehydes; D001688:Biological Products; C048069:flocoumafen; C024896:4-anisaldehyde; C068805:4-hydroxycoumarin