Total synthesis of Tetrodotoxin (Fukuyama):
| Reference: | Maehara, T,; Motoyama, K.; Toma, T.; Yokoshima, S.; Fukuyama, T Angew. Chem. Int. Ed. 2017, 56, 1549-1552.DOI |
| Reactions: | Luche reduction • Enone → Allyl-OH • O-H → O-SiMe2tBu • O-C(O)R → O-H • Li/Sn → Li-Ether • Diol-1,2 → Ketal • O-H → O-C(O)NR2 • Alkyne → Ene-cis (Lindlar) • O-SiMe2tBu → O-H • C-N-OR → C=N-OR • O-H → O-SiMe3 • Felkin-Anh Chelation • CarboxAcid → CarboxEster • Williamson esterification • Pinnick oxidation • N-H → N-C(O)OR • O-Bn → O-H • Yamaguchi lactonization • Lactone-6 • N-Boc → N-H • Diels-Alder, Quinone • Bicyclo(221) • Bicyclo(440) • Allyl-OH → Enone • Li-Ether+Ketone • Ketone+Li-Ether • Alkene → Diol-1,2 • CompOx-Alkene/Alkene+OsO4 • Diol-1,2 → Ketone-α-OR • Peterson → EnoateEster • CarboxEster enolate+Ketone • Retro-Diels-Alder → Diene • O-C(O)NR2 → O-C≡N • 2,3-Sigmatropic Cyanate • Isocyanate+ROM • Alkene → Diol-1,2 • Mg-Alkynyl+Aldehyde • Aldehyde+Mg-Alkynyl • Oxime → Nitrile oxide • Cycloaddition Nitrile oxide • Bicyclo(440) • Bicyclo(430)-aza • Bicyclo(430)-oxa • Ozonolysis • N-OR → N-H • AminoAlcohol-1,2 cleavage • N-Alloc → N-H • Aldehyde → Acetal(Me) • N-H → N-C(NR)NR2 • Guanidine synthesis • N-Cbz → N-H • O-H → O-C(O)R (asym) • Enzyme • CompNu-O-H/O-H+RC(O)X • Asymmetric desymmetrization • Ketal → Diol-1,2 • Alkyl-NR2 → Alkyl-OH • |
| Reagents: | Cyclopentadiene • Vinyl-OAc • Lipase • BH4-Na+, CeCl3 • SiMe2tBu-Cl • Carbonate, potassium • Cr2O7·2PyH (PDC) • SnBu3-CH2-OR • BuLi(n) • LiCH2-OR • OsO4, NMO • Acetone (react) • CrO3, H2SO4 (Jones) • SiMe3-CH2CO2Me • AlHiBu2 • Isocyanate • Acetic anhydride, trifluoro • NEtiPr2 • LiOtBu • OsO4, NMO • Pb(OAc)4 • Alkynyl-MgX • H2, Pd • Fluoride, cesium • SiMe3-Cl • LiCHR-Sulfonyl • LiNiPr2 • TsOH • Benzyl-X • BH4-Na+, NiCl2 • O3 • Chlorite, sodium • PBu3 • O=C(OAllyl)Cl (Alloc) • O=C(OAllyl)Cl (Alloc) • Pb(OAc)4 • HSiPhH2 • Pd(PPh3)4 • Nitrite, sodium • Orthoacetate • TsOH·Py • H2, Pd • DMAP • SiMe3-I • HgCl2 • NEt3 • Acetic acid, trifluoro • H2, Pd • |