Convergent total syntheses of gambierol and 16-epi-gambierol and their biological activities.
The convergent total syntheses of gambierol (1) and 16-epi-gambierol (2) have been achieved. The ABC and FGH ring segments 4 and 5 were prepared from known compounds 6 and 13, respectively, by linear manners. The fragments prepared were connected by our own synthetic strategy including the intramolecular allylation of alpha-acetoxy ether followed by ring-closing metathesis to furnish the octacyclic ether 3. The diiodoalkene 45, prepared from 3, was converted to the Z-iodoalkene 50 via a novel and stereoselective hydrogenolysis followed by deprotection. Construction of the triene side chain was performed by the modified Stille coupling of 50 with the Z-vinylic stannane 41 to afford 1. The similar transformations were carried out on the epimeric octacycle 34 to give 2, which showed no toxicity against mice at the concentration of 14 mg/kg.
D000818:Animals; D002922:Ciguatoxins / Q000138:chemical synthesis* / Q000633:toxicity; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000633:toxicity; D007536:Isomerism; D007928:Lethal Dose 50; D051379:Mice; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000633:toxicity; D035964:Oxocins
D002922:Ciguatoxins; D004988:Ethers, Cyclic; D011083:Polycyclic Compounds; C435770:gambierol; D035964:Oxocins