Sequential Metal Catalysis towards 7‐Oxostaurosporine and Its Non‐Natural Septanose Analogue

Abstract

We report sequential metal catalysis towards indolocarbazole glycosides. The signature event is highlighted by i) Pd0‐catalyzed addition of indolocarbazole to alkoxyallene combined with ring‐closing‐metathesis; ii) Ru‐catalyzed chemoselective olefin migration; iii) PdII‐catalyzed oxidative cyclization to build the bicyclic core structure of the target compounds. This approach gave access to both natural pyranose‐ and non‐natural septanose glycosides. A short formal synthesis of 7‐oxostaurosporine was achieved via this strategy.

Advancements in the synthesis of polyoxygenated oxepanes and thiepanes for applications to natural products

“…In 2022, Rhee and coworkers showcased the successful synthesis of an unnatural septanoside analog of 7-oxostaurosporine (517) via sequential metal catalysis (Scheme 69). 194 A palladium-catalyzed coupling of indolocarbazole 509 and alkoxyallene 510 was able to afford an acyclic allylic acetal 512 in near quantitative yield and in a 9 : 1 dr when ligand (R,R)-511 was used. Ring-closing metathesis (RCM) with the secondgeneration Hoveyda-Grubbs catalyst (HGII) was employed to form the seven-membered oxacycle, 513 which set the stage for a successful olefin migration facilitated by ruthenium hydride catalyst 514.…”

“…Next, a mercury vapor lamp is used to initiate a regioselective Schenck Scheme 69 Oxidative cyclization strategy to access unnatural analog to 7-oxostaurosporine. 194 Scheme 70 First reported total synthesis of (+)-artemisinin from (-)-isopulegol by Schmid and Hofheinz in 1983. 197 Scheme 71 Cook and coworkers' route to (+)-artemisinin.…”