RESUMO
Of the more than 100 casbane diterpenes known to date, only the eponymous parent hydrocarbon casbene itself has ever been targeted by chemical synthesis. Outlined herein is a conceptually new approach that brings not a single but a variety of casbane derivatives into reach, especially the more highly oxygenated and arguably more relevant members of this family. The key design elements are a catalyst-controlled intramolecular cyclopropanation with or without subsequent equilibration, chain extension of the resulting stereoisomeric cyclopropane building blocks by chemoselective hydroboration/cross-coupling, and the efficient closure of the strained macrobicyclic framework by ring-closing alkyne metathesis. A hydroxy-directed catalytic trans-hydrostannation allows for late-stage diversity. These virtues are manifested in the concise total syntheses of depressin, yuexiandajisuâ A, and ent-pekineninâ C. The last compound turned out to be identical to euphorhylonalâ A, the structure of which had clearly been misassigned.
RESUMO
A convergent, nine-step (LLS), enantioselective synthesis of α-cyclopiazonic acid and related natural products is reported. The route features a)â an enantioselective aziridination of an imine with a chiral sulfur ylide; b)â a bioinspired (3+2)-cycloaddition of the aziridine onto an alkene; and c)â installation of the acetyltetramic acid by an unprecedented tandem carbonylative lactamization/N-O cleavage of a bromoisoxazole.
RESUMO
The first enantioselective synthesis of a secalonic acid containing a dimeric tetrahydroxanthenone skeleton is described, using a Wacker-type cyclization of a methoxyphenolic compound to form a chiral chroman with a quaternary carbon stereogenic center with >99% ee. Further steps are a Sharpless dihydroxylation and a Dieckmann condensation to give a tetrahydroxanthenone. A late-stage one-pot palladium-catalyzed Suzuki-dimerization reaction leads to the 2,2'-biphenol linkage to complete the enantioselective total synthesis of secalonic acid E in 18â steps with 8% overall yield.