Collective Total Synthesis of Casbane Diterpenes: One Strategy, Multiple Targets

Abstract

Of the more than 100 casbane diterpenes knownt o date,o nly the eponymous parent hydrocarbon casbene itself has ever been targeted by chemical synthesis.Outlined herein is ac onceptually new approach that brings not as ingle but avariety of casbane derivatives into reach, especially the more highly oxygenated and arguably more relevant members of this family.T he key design elements are ac atalyst-controlled intramolecular cyclopropanation with or without subsequent equilibration, chain extension of the resulting stereoisomeric cyclopropane building blocks by chemoselective hydroboration/cross-coupling,a nd 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, yuexiandajisu A, and ent-pekinenin C. The last compound turned out to be identical to euphorhylonal A, the structure of which had clearly been misassigned.

Die Struktur des Cyclodecatriens Collinolacton, seine Biosynthese und semisynthetische Derivate: monopolare Spindeln und Schutz vor intrazellulärem oxidativem Stress

“…Wenn die Hydroxygruppe von Verbindung 1 mit 2‐Iodoxybenzoesäure (IBX) oxidiert wird, erhält man Verbindung 8 , wo die Bildung von Verbindung 7 nicht länger beobachtet werden konnte, da die Affinität zu Wasserstoffbrückenbildung von Hydroxygruppen im Vergleich zu Ketonen reduziert ist. Organokupfer‐Reagenzien wie Gilmann‐Cuprat und Strykers Reagenz tolerieren eine Vielzahl an funktionellen Gruppen wie Lactone und Alkene, was sie sehr nützlich für die Synthese von komplexen Naturstoffen macht [24] . Wir benutzten Gilmann‐Cuprat, um eine Methylgruppe an C9 einzuführen, was zu Verbindung 9 führte.…”

“…Organokupfer-Reagenzien wie Gilmann-Cuprat und Strykers Reagenz tolerieren eine Vielzahl an funktionellen Gruppen wie Lactone und Alkene, was sie sehr nützlich für die Synthese von komplexen Naturstoffen macht. [24] Wir benutzten Gilmann-Cuprat, um eine Methylgruppe an C9 einzuführen, was zu Verbindung 9 führte. Die Stereochemie wurde anschließend mittels NOESY-Korrelationen bestimmt.…”

From Serendipity to Rational Design: Heteroleptic Dirhodium Amidate Complexes for Diastereodivergent Asymmetric Cyclopropanation

“…The lessons to be learnt from it may therefore open new vistas for catalyst design and ultimately lead to strategic innovation in cyclopropanation chemistry in general. 36 , 37 …”

[Rh2(MEPY)4] and [BiRh(MEPY)4]: Convenient Syntheses and Computational Analysis of Strikingly Dissimilar Siblings

“…A recent approach to an ensemble of different casbane diterpenes including compounds 4 – 6 capitalized on the use of the cyclopropyl lactone 3 as a key building block [1] . This compound is readily accessible by intramolecular cyclopropanation of diazoester 2 using [Rh 2 (5 S ‐MEPY) 4 ] ⋅ (MeCN) 2 ⋅ i PrOH ( 1a ) as the catalyst; [2–12] in our hands, compound 3 was obtained in 87 % yield and 93 % ee ( Scheme 1).…”

“…This compound is readily accessible by intramolecular cyclopropanation of diazoester 2 using [Rh 2 (5 S ‐MEPY) 4 ] ⋅ (MeCN) 2 ⋅ i PrOH ( 1a ) as the catalyst; [2–12] in our hands, compound 3 was obtained in 87 % yield and 93 % ee ( Scheme 1). [1] …”