Synthesis of the ABC tricyclic fragment of the pectenotoxins via stereocontrolled cyclization of a gamma-hydroxyepoxide appended to the AB spiroacetal unit.
The stereocontrolled synthesis of the C1-C16 ABC spiroacetal-containing tricyclic fragment of pectenotoxin-7 6 has been accomplished. The key AB spiroacetal aldehyde 9 was successfully synthesized via acid catalyzed cyclization of protected ketone precursor 28 that was readily prepared from aldehyde 12 and sulfone 13. The syn stereochemistry in aldehyde 12 was installed using an asymmetric aldol reaction proceeding via a titanium enolate. The stereogenic centre in sulfone 13 was derived from (R)-(+)-glycidol. The absolute stereochemistry of the final spiroacetal aldehyde 9 was confirmed by NOE studies establishing the (S)-stereochemistry of the spiroacetal centre. Construction of the tetrahydrofuran C ring system began with Wittig olefination of the AB spiroacetal aldehyde 9 with (carbethoxyethylidene)triphenylphosphorane 10 affording the desired (E)-olefin 32. Appendage of a three carbon chain to the AB spiroacetal fragment was achieved via addition of acetylene 11 to the unstable allylic iodide 39. Epoxidation of (E)-enyne 8 via in situ formation of L-fructose derived dioxirane generated the desired syn-epoxide 36. Semi-hydrogenation of the resulting epoxide 36 followed by dihydroxylation of the alkene effected concomitant cyclization, thus completing the synthesis of the ABC spiroacetal ring fragment 6.
Department of Chemistry, University of Auckland, 23 Symonds St, Auckland, New Zealand.
Rosliana
R
Halim
Margaret A
MA
Brimble
Jörn
J
Merten
D004852:Epoxy Compounds / Q000737:chemistry*; D005663:Furans / Q000737:chemistry; D018942:Macrolides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008387:Marine Toxins / Q000138:chemical synthesis*; D008958:Models, Molecular; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry; D000095702:Polyether Toxins
D004852:Epoxy Compounds; D005663:Furans; D018942:Macrolides; D008387:Marine Toxins; D011714:Pyrans; D013141:Spiro Compounds; C471226:pectenotoxin-4; D000095702:Polyether Toxins; C051905:pectenotoxin 1; C098380:pectenotoxin 2