Halichondrin B: synthesis of the C(37)–C(54) subunit

Titanium reagents for the alkylidenation of carboxylic acid and carbonic acid derivatives

“…135 Desymmetrization of C 2 -symmetric bis(lactone) 185 by monomethylenation-hydroboration-oxidation is a key step in Burke's approach to marine polycyclic toxin, halichondrin B (Scheme 96). 136 Bis(lactone) 185 is treated with 0.6-0.7 eq. of Tebbe reagent, followed by hydroboration-oxidation to give Following the procedure developed by Rajanbabu and Reddy, 137 Potter and co-workers carried out Tebbe methylenation of sugar lactone 187 followed by stereoselective hydroboration with a bulky hydroborating agent, 9-BBN, and oxidation to give exclusively β-C-glucosides 188 (Scheme 97).…”

Desymmetrization of pibrentasvir for efficient prodrug synthesis

“…desymmetrized primary alcohol 8 in 40% yield. 12 In a remarkably brief route to (+)-roxaticin that showcases this approach, the Krische group desymmetrized diol 9 via mono-selenide 10 formation in 50% yield. 13 Our initial synthesis of prodrug 3 used a similar strategy, producing intermediate di-Bn-3 in only 19% yield from pibrentasvir.…”

“… 10 Two syntheses from the Burke group utilized this approach, including a related annonaceous acetogenin, uvaricin (not shown), using a dihydroxylation, 11 and the C(37)-C(54) halichondrin B subunit, using an olefination/hydroboration/oxidation sequence to convert bis(lactone) 7 to desymmetrized primary alcohol 8 in 40% yield. 12 In a remarkably brief route to (+)-roxaticin that showcases this approach, the Krische group desymmetrized diol 9 via mono-selenide 10 formation in 50% yield. 13 Our initial synthesis of prodrug 3 used a similar strategy, producing intermediate di-Bn-3 in only 19% yield from pibrentasvir.…”

Desymmetrization of Pibrentasvir for Efficient Prodrug Synthesis

“…10 Two syntheses from the Burke group utilized this approach, including a related annonaceous acetogenin, uvaricin (not shown), using a dihydroxylation, 11 and the C(37)-C(54) halichondrin B subunit, using an olefination/hydroboration/oxidation sequence to convert bis(lactone) 7 to desymmetrized primary alcohol 8 in 40% yield. 12 In a remarkably brief route to (+)-roxaticin that showcases this approach, the Krische group desymmetrized diol 9 via mono-selenide 10 formation in 50% yield. 13 In each example, a maximum yield of 50% was expected and observed due to the statistical mixtures of starting material/mono/di-functionalized products (1:2:1 ratio) obtained in homotopic termini differentiation, requiring starting material recovery and resubjection to improve material throughput.…”