Total Synthesis of Maximiscin, A Natural Product with Anticancer Properties

In this video, we explore the recent total synthesis of (-)-maximiscin by the Baran group.

Parent reference:
J. Am. Chem. Soc. 2020, 142, 8608-8613.
Additional references (in order of appearance):
For previous structural/synthetic work with pyridone alkaloids, see: Nat. Prod. Rep. 2010, 27, 1168-1185. For biological activity studies, see: (a) Tetrahedron 2004, 60, 9543-9558. (b) J. Nat. Prod. 2016, 79, 1822-1827.
For more on the Guareschi-Thorpe condensation, see: Name Reactions: A Collection of Detailed Reaction Mechanisms by Jie Jack Li.
For more on redox relay strategies in the context of steroid synthesis, see: J. Am. Chem. Soc. 2015, 137, 1330-1340.
For more on approaches to desymmetrization of meso compounds in total synthesis, see: Synthesis 2017, 49, 1938-1954.
For more on this hydrogenation, see: Cycloalkylamides and Their Therapeutic Applications. U.S. Patent Application 20040209858A1, 2003.
Development of this approach to C-H activation: (a) J. Am. Chem. Soc. 2004, 126, 2300-2301. (b) J. Am. Chem. Soc. 2012, 134, 7313-7316. (c) Chem. Sci. 2013, 4, 4187-4192. (d) Angew. Chem. Int. Ed. 2013, 52, 13606-13610.
For more on local desymmetrization by diastereotopic group discrimination, see: Eur. J. Org. Chem. 2017, 2017, 1381-1390.
Also see “Stereoisomerism and local chirality” by Mislow and Siegel: J. Am. Chem. Soc. 1984, 106, 3319-3328.
See supporting details of parent reference for optimization details. For more information on the role of Fe3+ in promoting oxidation of the α-oxy radical, see: Acc. Chem. Res. 1975, 8, 125-131.
For more information on the aerobic oxidation of sulfones to carboxylic acids, see: Org. Lett. 2011, 13, 1447-1449.
For more on Mander’s reagent, see: Synlett 1990, 1990, 169-170.
For prior synthesis of shikimic acid-derived epoxide, see: Org. Lett. 2014, 16, 3760-3763.
For more on the Hosomi-Sakurai reaction, see: (a) Acc. Chem. Res. 1988, 21, 200-206. (b) Bull. Chem. Soc. Jpn. 2004, 77, 835-851. For more on the β-silicon effect, see: Tetrahedron 1980, 36, 2215-2218.