Divergent Total Syntheses of Six Ganoderma Meroterpenoids: A Bioinspired Two-Phase Strategy

Abstract

We briefly highlight our recent work on the total synthesis of six Ganoderma phenolic meroterpenoids: ganocins A–C, ganocochlearins A–D, and cochlearol T. Critical to this success was a bioinspired two-phase strategy that featured an early-stage rapid construction of a common planar tricyclic intermediate and late-stage highly selective transformations of this intermediate into various Ganoderma meroterpenoids. Key steps of the synthesis include a biomimetic ortho-quinone methide intramolecular hetero-Diels–Alder reaction, a Stahl-type oxidative aromatization, a nucleophilic dearomatization of a phenol, a regioselective 1,4-reduction of a dienone, a site-selective Mukaiyama hydration, and an intramolecular oxa-Michael addition/triflation cascade.

Key words

divergent synthesis - meroterpenoids - biomimetic synthesis - total synthesis

• References

• 1a Hill RA, Connolly JD. Nat. Prod. Rep. 2013; 30: 1028
• 1b Baby S, Johnson AJ, Govindan B. Phytochemistry 2015; 114: 66
• 2 Peng X.-R, Liu J.-Q, Wan L.-S, Li X.-N, Yan Y.-X, Qiu M.-H. Org. Lett. 2014; 16: 5262
• 3a Peng X-R, Liu J.-Q, Wang C.-F, Han Z.-H, Shu Y, Li X.-Y, Zhou L, Qiu M.-H. Food Chem. 2015; 171: 251
• 3b Wang X.-L, Wua Z.-H, Di L, Zhou F.-J, Yan Y.-M, Cheng Y.-X. Phytochemistry 2019; 162: 199
• 4 Liu Y, Zhou C.-J, Li Q, Wang H. Org. Biomol. Chem. 2016; 14: 10362
• 5 Niu X.-M, Li S.-H, Sun H.-D, Che C.-T. J. Nat. Prod. 2006; 69: 1364
• 6 Shao H, Gao X, Wang Z.-T, Gao Z, Zhao Y.-M. Angew. Chem. Int. Ed. 2020; 59: 7419
• 7a Mukaiyama T, Narasaka K, Banno K. Chem. Lett. 1973; 2: 1011
• 7b Mukaiyama T, Banno K, Narasaka K. J. Am. Chem. Soc. 1974; 96: 7503

For selected recent reviews on o-QMs, see:
• 8a Van De Water RW, Pettus TR. R. Tetrahedron 2002; 58: 5367
• 8b Willis NJ, Bray CD. Chem. Eur. J. 2012; 18: 9160
• 8c Bai W.-J, David J.-G, Feng Z.-G, Weaver M.-G, Wu K.-L, Pettus T.-R. Acc. Chem. Res. 2014; 47: 3655
• 8d Wang Z, Sun J. Synthesis 2015; 47: 3629
• 8e Nielsen CD.-T, Abas H, Spivey AC. Synthesis 2018; 50: 4008
• 9a Izawa Y, Pun D, Stahl S. Science 2011; 333: 209
• 9b Diao T, Pun D, Stahl S. J. Am. Chem. Soc. 2013; 135: 8205
• 9c Pun D, Diao T, Stahl S. J. Am. Chem. Soc. 2013; 135: 8213
• 10 Li W, Li Y, Li Y. Org. Prep. Proced. Int. 1996; 28: 83
• 11a Arduengo AJ. III, Dias HV. R, Calabrese JC, Davidson F. Organometallics 1993; 12: 3405
• 11b Jurkauskas V, Sadighi JP, Buchwald SL. Org. Lett. 2003; 5: 2417
• 11c Hughes G, Kimura M, Buchwald SL. J. Am. Chem. Soc. 2003; 125: 11253

For metal-catalyzed olefin hydration, see:
• 12a Isayama S, Mukaiyama T. Chem. Lett. 1989; 18: 1071
• 12b Mukaiyama T, Isayama S, Inoki S, Kato K, Yamada T, Takai T. Chem. Lett. 1989; 18: 449
• 12c Inoki S, Kato K, Takai T, Isayama S, Yamada T, Mukaiyama T. Chem. Lett. 1989; 18: 515
• 12d Isayama S. Bull. Chem. Soc. Jpn. 1990; 63: 1305
• 12e Magnus P, Payne AH, Waring MJ, Scott DA, Lynch V. Tetrahedron Lett. 2000; 41: 9725
• 12f Magnus P, Scott DA, Fielding MR. Tetrahedron Lett. 2001; 42: 4127
• 13a Baillargeon VP, Stille JK. J. Am. Chem. Soc. 1983; 105: 7175
• 13b Baillargeon VP, Stille JK. J. Am. Chem. Soc. 1986; 108: 452