title: Direct assembly of multiply oxygenated carbon chains by decarbonylative radical-radical coupling reactions.
abstract: Pentoses and hexoses contain more than three oxygen-bearing stereocentres and are ideal starting materials for the synthesis of multiply oxygenated natural products such as sagittamide D, maitotoxin and hikizimycin. Here we demonstrate new radical-radical homocoupling reactions of sugar derivatives with minimal perturbation of their chiral centres. The radical exchange procedure using Et3B/O2converted sugar-derived α-alkoxyacyl tellurides into α-alkoxy radicals via decarbonylation and rapidly dimerized the monomeric radicals. The robustness of this process was demonstrated by a single-step preparation of 12 stereochemically diverse dimers with 6-10 secondary hydroxy groups, including the C5-C10 stereohexad of sagittamide D and the enantiomer of the C51-C60 stereodecad of maitotoxin. Furthermore, the optimally convergent radical-radical cross-coupling reaction achieved a one-step assembly of the protected C1-C11 oxygenated carbon chain of the anthelmintic hikizimycin. These exceptionally efficient homo- and heterocoupling methods together provide a powerful strategy for the expedited total synthesis of contiguously hydroxylated natural products.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masanori
authors.identifier: 0000-0001-9204-194X
authors.initials: M
authors.lastname: Nagatomo
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry*; D008387:Marine Toxins / Q000737:chemistry; D009952:Ornithine / Q000737:chemistry; D035964:Oxocins / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism; D000095702:Polyether Toxins
chemical_list: D000617:Aminoglycosides; D002244:Carbon; D005609:Free Radicals; D008387:Marine Toxins; D009952:Ornithine; D035964:Oxocins; D010100:Oxygen; C010186:hikizimycin; C020394:maitotoxin; D000095702:Polyether Toxins