Total Synthesis of Schilancitrilactones B and C

Abstract

The first total syntheses of schilancitrilactones B and C have been accomplished in 17 steps (longest linear sequence) from commercially available materials. Key steps include an intramolecular radical cyclization to provide the seven-membered ring, late-stage iodination, and an intermolecular radical addition reaction to complete the total synthesis.Schilancitrilactones B and C (1 and 2; Figure 1) [1] were isolated in 2012 by Sun and co-workers from the stems of Schisandra Lancifolia, which have been used in traditional Chinese medicine for the treatment of neurasthenia and related diseases.[2] Preliminary biological assays indicated that schilancitrilactone C showed biological activities for inhibiting HIV-1 while schilancitrilactone B was not bioactive. The structures of these compounds were striking in that they contain a 5/7/5/5/5-fused pentacyclic ring system bearing nine stereogenic centers. In addition, the three cis-fused fivemembered rings (rings C-E), all with the envelope conformations, and seven contiguous chiral centers (including two quaternary centers) form a structurally rigid tricyclic ring system. Construction of these highly oxygenated unique motifs remains challenging. Herein, we present the first total synthesis of schilancitrilactones B and C. The key steps include the successful implementation of an intramolecular radical cyclization to prepare a seven-member ring, late-stage iodination, and an intermolecular radical CÀC bond formation.

Development of Biomimetic Synthesis of Propindilactone G†

“…Following the pioneering synthesis of schinortriterpenoid schindilactone A [4a] by Yang [ 4 ] and co‐workers in 2011, the elegant total syntheses of several other members were achieved in the past decade, including Yang's total syntheses of propindilactone G [4b] (2015), 19‐dehydroxyl arisandilactone A [4c] (2017), lancifodilactone G acetate [4d] (2018), and pre‐schisanartanin C [4e] (2019); Li's total syntheses [ 5 ] of rubriflordilactone A [5a] (2014), rubriflordilactone B [5b] (2016), and pseudo ‐rubriflordilactone B [5c] (2019); Anderson's total syntheses [ 6 ] of rubriflordilactone A [6a,6b] (2015), rubriflordilactone B [6c] (2019), and pseudo ‐rubriflordilactone B [6c] (2019); Tang's total syntheses [ 7 ] of schilancitrilactones B and C [7a] (2015), schilancitrilactone A [7b] (2017), and schilancidilactones A and B [7b] (2017); and Ding's total synthesis of atrop‐schiglautone A [8] (2018).…”

Novel A-seco-nortriterpenoids from Ganoderma cochlear inhibiting Tau pathology by activating AMPK-ULK1-mediated autophagy

“…Ganoderma has attracted significant attention from pharmacologists, chemists, and phytochemists because it has long been used as a traditional medicine in many countries 1,2 and is also an important source of meroterpenoids and lanostane triterpenoids with significant bioactivities and captivating structures. 3–9 In particular, Ganoderma triterpenoids (GTs) have been widely studied as the main active constituents of Ganoderma for their anti-tumor, anti-aging, liver-protective, and neuroprotective activities. Notably, previous studies have confirmed that GTs can reverse cognitive impairment, 10 attenuate LPS-induced inflammation and apoptosis, 11 promote amyloid-β clearance and inhibit Tau pathology through activating autophagy, 6,12 suggesting that GTs exhibit huge potential in the treatment of neurodegenerative diseases.…”