Stereocontrolled total syntheses of isodomoic acids G and H via a unified strategy.
Marine neuroexcitatory compounds isodomoic acids G and H were efficiently synthesized from a common intermediate using a silicon-based cross-coupling reaction. Dividing each target compound into the core fragment and the side-chain fragment enabled the synthesis to be convergent. The trans-2,3-disubstituted pyrrolidine core fragment was accessed through a diastereoselective rhodium-catalyzed carbonylative silylcarbocyclization reaction of a vinylglycine-derived 1,6-enyne. A stereochemically divergent desilylative iodination reaction was developed to convert the cyclization product to both E- and Z-alkenyl iodides, which would eventually lead to isodomoic acid G and isodomoic acid H, respectively. The late-stage alkenyl-alkenyl silicon-based cross-coupling reaction uniting the core alkenyl iodides and the side-chain alkenylsilanol was achieved under mild conditions. Finally, two mild deprotections afforded the target molecules.
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA. sdenmark@illinois.edu
Scott E
SE
Denmark
Jack Hung-Chang
JH
Liu
Joseck M
JM
Muhuhi
D000475:Alkenes / Q000737:chemistry; D003432:Cross-Linking Reagents; D003500:Cyclization; D006538:Heptanoic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification; D015394:Molecular Structure; D012825:Silicon / Q000737:chemistry; D013237:Stereoisomerism
D000475:Alkenes; D003432:Cross-Linking Reagents; D006538:Heptanoic Acids; C547165:isodomoic acid G; C547164:isodomoic acid H; D012825:Silicon