A novel route to the F-ring of halichondrin B. Diastereoselection in Pd(0)-mediated meso and C(2) biol desymmetrization.
Both sigma and C(2) symmetric diol diacetates were synthesized via two-directional chain elongation. A palladium-mediated, ligand-controlled C(2) diol desymmetrization provided the desired tetrahydrofuran with the correct relative and absolute stereochemistries. Simple functional group manipulation led to the desired F-ring of halichondrin B. Desymmetrization of the meso substrate enantioselectively provided the diastereomer, leading to a refinement of our understanding of the transition state model. [reaction: see text]
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D018942:Macrolides; D008968:Molecular Conformation; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism; D014961:X-Ray Diffraction; D000095662:Polyether Polyketides
D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D018942:Macrolides; D010165:Palladium; C070519:halichondrin B; D000095662:Polyether Polyketides