Studies on the synthesis of (-)-gymnodimine. Subunit synthesis and coupling.
Two principal subunits of the marine algal toxin (-)-gymnodimine were synthesized. A trisubstituted tetrahydrofuran representing C10-C18 of the toxin was prepared via a highly stereoselective iodine-mediated cyclization of an acyclic alkene bearing a bis-2,6-dichlorobenzyl (DCB) ether. The formation of a cis-2,5-disubstituted tetrahydrofuran in this process conforms to a stereodirecting effect by the DCB group proposed by Bartlett and Rychnovsky. A cyclohexene subunit corresponding to the C1-C8, C19-C24 portion of gymnodimine was synthesized via Diels-Alder cycloaddition of a 1,2,3-trisubstituted diene to a symmetrical dienophile obtained from Meldrum's acid. Differentiation of carbonyl groups in the cycloadduct was made by an intramolecular reaction with a neighboring alcohol to form a gamma-lactone. Linkage of the two subunits at C18-C19 was accomplished by using a B-alkyl Suzuki coupling in which a borane prepared from the pendent alkenyl chain of the cyclohexene domain was reacted with the (E)-iodoalkene attached at C16 of the tetrahydrofuran sector. Subsequent transformations positioned functional groups in the coupled product for a future macrocyclization event that would close the 15-membered ring of gymnodimine.
White
James D
JD
Department of Chemistry, Oregon State University, Corvallis, OR 97331-4003, USA. james.white@oregonstate.edu
Quaranta
Laura
L
Wang
Guoqiang
G
D018360:Crystallography, X-Ray; D053138:Cyclohexenes / Q000138:chemical synthesis; D005663:Furans / Q000138:chemical synthesis; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis*; D006844:Hydrocarbons, Cyclic / Q000138:chemical synthesis*; D007097:Imines / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008387:Marine Toxins / Q000138:chemical synthesis*; D008968:Molecular Conformation; D013237:Stereoisomerism
D053138:Cyclohexenes; D005663:Furans; D006575:Heterocyclic Compounds, 3-Ring; D006844:Hydrocarbons, Cyclic; D007097:Imines; D007202:Indicators and Reagents; D008387:Marine Toxins; C407350:gymnodimine