Total Synthesis of the Cyathane Diterpenoid (±)-Sarcodonin G

Abstract

[process--see text] The total synthesis of (+/-)-sarcodonin G (3), a highly functionalized member of the cyathane family of diterpenoids, is described.

7-6-5 Tricarbocyclic Diterpenes

“…5.6 by the exciton chirality method [54]. Since the 1970s, a large number of compounds with a cyathane skeleton have been isolated, so this nomenclature became obsolete; and, as the number of diterpenes increased they were incorporated into new groups with different names, such as cyafrins, sarcodonins, scabronines, erinacines, Sarcodonins, Neosarcodonins [66][67][68][69][70][71][72]75], and Scabronines [73,74,[76][77][78][79][80][81][82] Sarcodonins, neosarcodonins, and scabronines are compounds with cyathane skeletons, isolated from the fungus Sarcodon scabrosus (Fig. The natural products with 20 carbons and 30 hydrogens are classified as cyathins A series; the ones with 28 hydrogens are series B, and ones with 26 hydrogens are classified as series C. The subscript after the letter refers to the number of oxygens in the molecules.…”

“…The first members of this group (sarcodonin A 113 and sarcodonin G 114) were isolated from the fungus S. scabrosus in 1989 by Shibata and coworkers [66]. In 2000, the same authors described the synthesis of (AE) sarcodonin G 114 [68]. However, in the same publication, it includes a perspective drawing obtained by X-ray analysis where it clearly states the configuration at C18 of sarcodonin G as S. The configuration at C18 as S, of these compounds, was confirmed by Piers and coworkers through X-ray diffraction of a sarcodonin G derivative [67].…”

Synthetic efforts toward cyathane diterpenoid natural products

“…The first total synthesis of sarcodonin G was described by Piers in 2000 26. Their approach to this cyathane diterpenoid targeted the tricyclic core with an alkylation and ring-expansion strategy, and employed late-stage installation of the periperhal functionality.…”

Synthetic Studies on Cyathin Terpenoids: Enantioselective Synthesis of the Tricyclic Core of Cyathin through Intramolecular Heck Cyclisation

“…The potential therapeutic relevance and the unique synthetic challenges provided by these molecules attracted intense efforts from a number of research teams since the disclosure of their structures. However, only few total syntheses of natural cyathins have been completed, namely (±)-allocyathin B 2 and (+)-erinacine A by the groups of Snider [8] and Tori [9] in 1996 and 1998, (±)-sarcodonin G by Piers's team, [10] (±)-allocyathin B 3 by the group of Ward in 2000, [11] (+)-allocyathin B 2 (2) by the groups of Nakada [12] in 2004 and Trost in 2005 [13] and finally (-)-scabronine G by Danishefsky [14] in 2005. Besides these successful syntheses, a large number of approaches have been proposed over the past decade.…”