5 Ferrier反応を鍵反応とした糖質からの天然物合成(口頭発表の部)

抄録

Ferrier rearrangement is one of the most efficient reactions for the synthesis of optically active substituted cyclohexanones from corresponding carbohydrates. We have found that the Ferrier rearrangement proceeds in high yields with a catalytic amount of (CF_3CO_2)_2Hg in a neutral solvent system. In this paper, chiral syntheses of natural products starting from D-glucose utilizing catalytic Ferrier rearrangement as the key reaction are described. Total Synthesis of (-)-Hygromycin A (15). Hygromycin A (15) is an antibiotic produced by Streptomyces and possesses a unique structure. The aminocyclitol moiety (13) was prepared from D-glucose. Catalytic Ferrier rearrangement of 3, synthesized in 7 steps from D-glucose, followed by β-elimination afforded the cyclohexenone 5. Luche reduction of 5 and the introduction of an amino function gave 9. Glycolation with OsO_4 and a methylene acetal formation, followed by deprotection provided the aminocyclitol 13. Condensation of 13 with the sugar carboxylic acid 14, followed by deprotection completed the first total synthesis of (-)-hygromycin A. Formal Total Synthesis of Paniculide A (28). Catalytic Ferrier rearrangement of the bicyclic enopyranoside 21, prepared from D-glucose in 10 steps, followed by β-elimination gave a cyclohexenone 22. 1,4-Addition of a methyl group and successive Saegusa reaction gave the optically active enone 24, which was converted into the known synthetic intermediate 27, for highly oxygenated sesquiterpene, (±)-paniculide A 28. Stereoselective Total Synthesis of (+)-Lycoricidine (41). The phenanthridone alkaloid, (+)-lycoricidine 41 is known to show high cytotoxic activity. The 2-azido-5-enopyranoside derivative 31, prepared from D-glucose in 9 steps, was effectively converted into the enone 32 by catalytic Ferrier rearrangement and subsequent β-elimination. The compound 32 was converted into fully protected bromo-olefin 35, which was cyclized by Pdcatalyzed reaction to provide the phenanthridone 37. Inversion of the configuration of 2-hydroxy group and the removal of the protecting group completed the total synthesis (+)-lycoricidine.