A preliminary evaluation of a metathesis approach to bryostatins

Cleavage of a chiral auxiliary using RCM on an especially sterically crowded alkene: Syntheses of chiral carbo- and heterocycles

“…The center example is perhaps closer to our own work in that it clearly shows the detrimental effect (presumably for steric reasons) of substituents around the diene framework on the formation of dihydropyrans 12 [9]. Thomas and co-workers have shown that the presence of a gem-dimethyl group at the allylic position of a terminal double bond shuts down a metathetic macrocyclization (not shown) [10]. A difficult RCM was successfully achieved from 13 by microwave irradiation as well as N 2 sparging to remove ethylene (Scheme 2, bottom) [11].…”

Total Synthesis of Bryostatin 9

“…19 Additionally, a formal total synthesis of bryostatin 7 was reported by Hale and colleagues in 2006. 20 Several additional groups have also made noteworthy contributions to this field, including those of Thomas, 21 Vandewalle, 22 Roy, 23 Burke, 24 Krische, 25 Hoffmann, 26 Yadav, 27 and others. 28 …”

Total synthesis of bryostatin 16 using atom-economical and chemoselective approaches

“…As an example, the challenge posed by the C16–17 double bond led to failure in routes relying on its formation by metathesis reactions17, even in the case of a relay metathesis strategy16. Despite their biological, clinical and structural significance, to date only three of the twenty bryostatins have been accessed by total synthesis (bryostatin 7 by Masamune9, bryostatin 2 by Evans10, and bryostatin 3 by Nishiyama and Yamamura11).…”

“…The 4-methylene-2,6- cis -tetrahydropyran moiety in intermediate 6 provides a perfect opportunity to examine our Ru-catalyzed alkene-alkyne coupling/Michael addition methodology21 between two complex fragments ( 7 and 8 ) aiming to address some chemoselectivity challenges. Given the difficulty to form the sterically hindered C16–17 olefin in the late stage (either by Julia olefination10 or ring-closing metathesis16,17), alkyne 8 was specifically designed to install this trans alkene in an early stage.…”