Mimicking Biosynthesis: Total Synthesis of the Triterpene Natural Product Abudinol B from a Squalene‐like Precursor

The development of endo-selective epoxide-opening cascades in water

“…lviii These Lewis acid-promoted cascades, each of which involves the opening of multiple epoxides, build on earlier studies from the McDonald group on the cascade synthesis of fused oxepane systems 28. An early cascade reaction of diepoxide 84 rapidly assembles tricycle 85 in 50% yield (79% average yield per ring), and the two remaining rings of ent -abudinol ( 87 ) are constructed in short order via a second cascade of diepoxy alkene 86 , in 15% yield (39% average per ring).…”

Biomimetic Synthesis of Polyether Natural Products via Polyepoxide Opening

“…Elegant work on ent-abudinol B and the related terpenes ent-durgamone and ent-nakorone capitalizing on studies of epoxide-opening cascades directed toward synthesis of ladder polyether structures was reported by McDonald [182,183]. In their first-generation approach to ent-abudinol B, McDonald and coworkers devised a convergent synthetic scheme featuring a late-stage coupling of fragments derived from ent-durgamone and ent-nakorone (156 and 159, Scheme 15.12a) [182].…”

“…An analogous strategy was utilized in the synthesis of the more complex ent-nakorone, but a hybrid cascade of oxacyclizations and carbocyclizations was required. Diepoxide 157, with a terminating propargyl silane nucleophile, [182]; (b) biomimetic approach [183]. DTBMP = 2,6-di-tert-butyl-4-methylpyridine.…”

“…A second-generation approach was based on the proposed biosynthetic pathway to ent-abudinol [2,73,74], which involves a hybrid cascade of epoxide openings and carbocyclizations [183]. Similar to the first-generation approach, diepoxide 160 was treated with TMSOTf to produce 161, containing the tricyclic fragment of ent-abudinol (Scheme 15.12b).…”

Organocatalytic Oxidation. Ketone‐Catalyzed Asymmetric Epoxidation of Alkenes and Synthetic Applications

“…In their second generation synthesis of ent-abudinol B (97) (Scheme 3.33) [68], farnesyl acetate 99 was selectively epoxidized at the two alkenes with ketone 42 and transformed into compound 101 via bromide 100. The cyclization of compound 101 with TMSOTf gave tricyclic compound 102, which was alkenated and preferentially epoxidized at the two trisubstituted alkenes with ketone 42 by careful control of the reaction conditions, leaving the 1,1-disubstituted alkene intact.…”