Total Synthesis of (±)-Leonuketal

Abstract

Cleavage of a C-C bond is a diversifying process in the biogenesis of seco-terpenoids that has produced fascinating molecular structures. Leonuketal is an 8,9-seco-labdane terpenoid with a unique tetracyclic structure, owing to a C-C bond cleavage event in its biosynthesis. We report the first total synthesis of leonuketal, featuring an unusual Shapiro-type reaction as part of an enabling auxiliary ring strategy, and a novel Au-catalysed spirocyclisation of a -keto(enol)lactone. ASSOCIATED CONTENTSupporting Information. The Supporting Information is available free of charge Experimental procedures, analytical data ( 1 H and 13 C NMR, MS, IR) for all compounds (PDF) Crystallographic information for compound 13 (CIF) Crystallographic information for compound 18 (CIF) Crystallographic information for compound 25 (CIF)

Total Synthesis of Spiroketal Alkaloids Lycibarbarines A–C

“…Our group has had a long-standing interest in spiroketal-containing natural products, due to their attractive bioactivities, ,, and the privileged nature − of the spiroketal scaffold. We have accomplished the total synthesis of several spiroketal-containing natural products, − including acortatarin A and pollenopyrroside A, which are structurally similar with 1 – 3 .…”

seco‐Labdanes: A Study of Terpenoid Structural Diversity Resulting from Biosynthetic C−C Bond Cleavage

“…Additionally, 105 was subjected to in vitro cytotoxicity assays against four human cancer cell lines (A549, MCF‐7, HepG‐2 and MDA‐MB‐231) and displayed no activity [84] . The total synthesis of leonuketal ( 105 ) was achieved by Brimble and co‐workers in 2020 and is discussed in Section 3.14 [97, 98] …”

“…reported the first total synthesis of leonuketal ( 105 ) by a strategy distinct from their preliminary investigations (Scheme 15 B). [97, 98] The synthesis commenced with the Ti III ‐mediated cyclisation of epoxide 275 to afford 276 with the formation of three chiral centres [136, 137] . Inversion of the C7 alcohol was then effected, delivering 277 , which served as the substrate for a pivotal Shapiro‐type reaction.…”

Total Synthesis of Spiroketal Alkaloids Lycibarbarines A–C

“…3,5 Our group has had a longstanding interest in spiroketalcontaining natural products, due to their attractive bioactivities, 3,6,7 and the privileged nature [8][9][10] of the spiroketal scaffold. We have accomplished the total synthesis of several spiroketal-containing natural products, [11][12][13][14][15] including acortatarin A 16 and pollenopyrroside A, 17 which share structural similarities with 1-3. We were intrigued by the lycibarbarines because they appeared to represent kinetic [5,6]-and thermodynamic [6,6]spiroketal products derived from the same oxocarbenium precursor 4 (Scheme 1).…”