title: Enantioselective halocyclization of polyprenoids induced by nucleophilic phosphoramidites.
abstract: Polycyclic bio-active natural products that contain halogen atoms have been isolated from a number of different marine organisms. The biosynthesis of these natural products appears to be initiated by an electrophilic halogenation reaction at a carbon-carbon double bond via a mechanism that is similar to a proton-induced olefin polycyclization. Enzymes such as haloperoxidases generate an electrophilic halonium ion (or its equivalent), which reacts with the terminal carbon-carbon double bond of the polyprenoid, enantioselectively inducing a cyclization reaction that produces a halogenated polycyclic terpenoid. Use of an enantioselective halocyclization reaction is one possible way to chemically synthesize these halogenated cyclic terpenoids; although several brominated cyclic terpenoids have been synthesized via a diastereoselective halocyclization reaction that uses stoichiometric quantities of a brominating reagent, the enantioselective halocyclization of isoprenoids induced by a chiral promoter has not yet been reported. Here we report the enantioselective halocyclization of simple polyprenoids using a nucleophilic promoter. Achiral nucleophilic phosphorus compounds are able to promote the diastereoselective halocyclization reaction to give a halogenated cyclic product in excellent yields. Moreover, chiral phosphoramidites promote the enantioselective halocyclization of simple polyprenoids with N-iodosuccinimide to give iodinated cyclic products in up to 99% enantiomeric excess and diastereomeric excess. To the best of our knowledge, this is the first successful example of the enantioselective halopolycyclization of polyprenoids.
authors.affiliation: Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sakakura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ukai
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ishihara
mesh_terms: D032701:Biomimetics; D002384:Catalysis; D003500:Cyclization; D006219:Halogens / Q000737:chemistry*; D007455:Iodine / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010544:Peroxidases / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D006219:Halogens; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D007455:Iodine; D010544:Peroxidases