Total synthesis of the spirocyclic imine marine toxin (-)-gymnodimine and an unnatural C4-epimer.
J Am Chem Soc
; 133(49): 19844-56, 2011 Dec 14.
Article
in En
| MEDLINE
| ID: mdl-22023219
ABSTRACT
The first total synthesis of the marine toxin (-)-gymnodimine (1) has been accomplished in a convergent manner. A highly diastereo- and enantioselective exo-Diels-Alder reaction catalyzed by a bis-oxazoline Cu(II) catalyst enabled rapid assembly of the spirocyclic core of gymnodimine. The preparation of the tetrahydrofuran fragment utilized a chiral auxiliary based anti-aldol reaction. Two major fragments, spirolactam 56 and tetrahydrofuran 55, were then coupled through an efficient Nozaki-Hiyama-Kishi reaction. An unconventional, ambient temperature t-BuLi-initiated intramolecular Barbier reaction of alkyl iodide 64 was employed to form the macrocycle. A late stage vinylogous Mukaiyama aldol addition of a silyloxyfuran to a complex cyclohexanone 83 appended the butenolide, and a few additional steps provided (-)-gymnodimine (1). A diastereomer of the natural product was also synthesized, C4-epi-gymnodimine (90), derived from the vinylogous Mukaiyama aldol addition.
Full text:
1
Database:
MEDLINE
Main subject:
Heterocyclic Compounds, 3-Ring
/
Hydrocarbons, Cyclic
/
Imines
/
Marine Toxins
Limits:
Animals
Language:
En
Year:
2011
Type:
Article