title: Total synthesis and structural elucidation of azaspiracid-1. Final assignment and total synthesis of the correct structure of azaspiracid-1.
abstract: The molecular structure of azaspiracid-1, a neurotoxin isolated from mussels, has been elucidated by total synthesis which also enriched its supplies. The degradatively derived fragments of this marine biotoxin, compounds 5 (EFGHI), 6 (FGHI), and 40 (ABCD), were matched with synthetic materials, thus confirming their structural identities. Based on this detective work, a new structure of azaspiracid-1 (i.e., 1) was proposed and constructed by total synthesis. The final strategy for the total synthesis of azaspiracid-1 featured a dithiane anion (C(21)-C(27) fragment) reacting with a pentafluorophenol ester (C(1)-C(20) fragment) followed by a Stille-type union of an advanced allylic acetate substrate (C(1)-C(27) fragment) with a vinyl stannane as the main coupling processes to assemble the carbon skeleton of the molecule. In addition to the total synthesis of azaspiracid-1 (1), the syntheses of its C(1)-C(20) epimer (2) and of several truncated analogues for biological investigations are described.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. kcn@scripps.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.forename: Theocharis V
authors.initials: TV
authors.lastname: Koftis
authors.forename: Stepan
authors.initials: S
authors.lastname: Vyskocil
authors.forename: Goran
authors.initials: G
authors.lastname: Petrovic
authors.forename: Wenjun
authors.initials: W
authors.lastname: Tang
authors.forename: Michael O
authors.initials: MO
authors.lastname: Frederick
authors.forename: David Y-K
authors.initials: DY
authors.lastname: Chen
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Li
authors.forename: Taotao
authors.initials: T
authors.lastname: Ling
authors.forename: Yoichi M A
authors.initials: YM
authors.lastname: Yamada
mesh_terms: D000818:Animals; D049872:Bivalvia / Q000737:chemistry; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D000095702:Polyether Toxins
chemical_list: D008387:Marine Toxins; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins