title: Total synthesis of (+)-azaspiracid-1. An exhibition of the intricacies of complex molecule synthesis.
abstract: The synthesis of the marine neurotoxin azaspiracid-1 has been accomplished. The individual fragments were synthesized by catalytic enantioselective processes: A hetero-Diels-Alder reaction to afford the E- and HI-ring fragments, a carbonyl-ene reaction to furnish the CD-ring fragment, and a Mukaiyama aldol reaction to deliver the FG-ring fragment. The subsequent fragment couplings were accomplished by aldol and sulfone anion methodologies. All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. A final fragment coupling of the anomeric EFGHI-sulfone anion to the ABCD-aldehyde completed the convergent synthesis of (+)-azaspiracid-1.
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. evans@chemistry.harvard.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Evans
authors.forename: Lisbet
authors.initials: L
authors.lastname: Kvaernø
authors.forename: Travis B
authors.initials: TB
authors.lastname: Dunn
authors.forename: André
authors.initials: A
authors.lastname: Beauchemin
authors.forename: Brian
authors.initials: B
authors.lastname: Raymer
authors.forename: Jason A
authors.initials: JA
authors.lastname: Mulder
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Olhava
authors.forename: Martin
authors.initials: M
authors.lastname: Juhl
authors.forename: Katsuji
authors.initials: K
authors.lastname: Kagechika
authors.forename: David A
authors.initials: DA
authors.lastname: Favor
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000838:Anions / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D002614:Chelating Agents / Q000737:chemistry; D017613:Iodine Compounds / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry; D008745:Methylation; D008958:Models, Molecular; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013450:Sulfones / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry; D000095702:Polyether Toxins
chemical_list: D000447:Aldehydes; D000838:Anions; D002244:Carbon; D002614:Chelating Agents; D017613:Iodine Compounds; D008387:Marine Toxins; D013141:Spiro Compounds; D013450:Sulfones; D014753:Vinyl Compounds; C406592:azaspiracid; D000095702:Polyether Toxins