title: Total synthesis of the marine alkaloid halichlorine: development and use of a general route to chiral piperidines.
abstract: The total synthesis of the marine alkaloid halichlorine is described, based on an approach that involves constructing the fully substituted asymmetric center at an early stage. The five-membered ring is formed by 5-exo-trig radical cyclization and the unsaturated six-membered ring by a process that formally represents a sequential combination of conjugate addition and S(N)2' displacement-a method that is general for making bicyclic compounds with nitrogen at a ring fusion position. A formal synthesis of (+)-halichlorine is also reported, based on the development of a general method for preparing optically pure piperidines. The key step of this method, which was used to make one of our intermediates, is the Claisen rearrangement of a 4-vinyloxy-3,4-dihydro-2H-pyridine-1-carboxylic acid benzyl ester. Such O-vinyl compounds are easily generated in situ from the corresponding alcohols, which are themselves readily assembled from serine and terminal acetylenes.
authors.affiliation: Chemistry Department, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Dazhan
authors.initials: D
authors.lastname: Liu
authors.forename: Hukum P
authors.initials: HP
authors.lastname: Acharya
authors.forename: Maolin
authors.initials: M
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Vince S C
authors.initials: VS
authors.lastname: Yeh
authors.forename: Shunzhen
authors.initials: S
authors.lastname: Kang
authors.forename: Chandramouli
authors.initials: C
authors.lastname: Chiruta
authors.forename: Santosh M
authors.initials: SM
authors.lastname: Jachak
authors.forename: Derrick L J
authors.initials: DL
authors.lastname: Clive
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D008968:Molecular Conformation; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D010880:Piperidines; D013141:Spiro Compounds; C412666:halichlorine