Synthetic studies on roseophilin, pentalongin and selected angucyclines.

摘要

Synthetic studies on roseophilin, pentalongin and two angucyclines are described.; Part I. Roseophilin: Two different model studies were tested to synthesize the polycyclic core 1.2 of roseophilin.; The first one was based on the [5,5]oxy-Cope rearrangement. Tetraenol 1.58 was prepared in five steps from norcamphor. The oxy-Cope rearrangement of 1.58, which was attempted under various conditions, did not give the rearrangement product 1.59.; In the second approach, oxidative cleavage of the bicyclic compound 1.87, prepared from cyclododecanone, was used to synthesize the key intermediate diketone 1.88. While OsO₄/NaIO₄ gave no product, ozonolysis provided a 10% yield of 1.88.; Part II. Pentalongin: A concise synthesis of pentalongin was described and it also provided a general route to synthesize several closely related compounds. The key intermediate 2.41 was prepared in five steps from sulfone 2.31. Claisen rearrangement of 2.41 followed by protection of the two OH groups and oxidative cleavage of the olefin afforded the aldehyde 2.46, which was converted into pentalongin (2.6) by acid catalyzed cyclization, CAN oxidation and elimination of methanol.; Part III. Angucyclines: Tetrangulol (3.5) and its de-methoxy analog 3.113 were successfully synthesized. A biomimetic approach to linear and angular polyketide derived natural products was investigated. In these studies, an olefin and an isoxazole ring were used as latent carbonyl functionality. Acid cyclization of 3.107 and 3.137 furnished the angularly cyclized products 3.108 and 3.138. Further cyclization of 3.108 and 3.138 with K₂CO₃ in methanol cleanly afforded the desired products 3.109 and 3.139, which were efficiently converted to 3.113 and tetrangulol (3.5) in four steps.