Bioinspired Total Synthesis of Marine Anticancer Meroterpenoids Dysideanone B and Dysiherbol A and Structure Revision of Dysiherbol A

Abstract

Our recent progress on the total synthesis of marine anticancer sesquiterpene quinone/hydroquinone dysideanone B and dysiherbol A is briefly highlighted. This success relied on some key transformations. The union of the terpene and quinone/hydroquinone moieties was realized through a site and stereoselective α-position alkylation of Wieland–Miescher ketone derivative with a bulky benzyl bromide. The 6/6/6/6-tetracycle of dysideanone B was constructed using an intramolecular radical cyclization and the 6/6/5/6-fused core structure of dysiherbol A was forged by an intramolecular Heck reaction, respectively. The possible origin of ethoxy group in dysideanone B was revealed by mimicking the isolation conditions at a late stage. The structure of dysiherbol A was revised through the total synthesis of this natural product. Schmalz’s synthesis of dysiherbol A was also included.

Key words

dysideanone B - dysiherbol A - meroterpenoid - natural product - structure revision - total synthesis

• References

• 1a García PA, Hernández ÁP, San Feliciano A, Castro M. Á. Mar. Drugs 2018; 16: 292
• 1b Gordaliza M. Mar. Drugs 2010; 8: 2849
• 1c Marcos IS, Conde A, Moro RF, Basabe P, Diez D, Urones JG. Mini-Rev. Org. Chem. 2010; 7: 230
• 2 Jiao W.-H, Xu T.-T, Yu H.-B, Chen G.-D, Huang X.-J, Yang F, Li Y.-S, Han B.-N, Liu X.-Y, Lin H.-W. J. Nat. Prod. 2014; 77: 346
• 3 Jiao W.-H, Shi G.-H, Xu T.-T, Chen G.-D, Gu B.-B, Wang Z, Peng S, Wang S.-P, Li J, Han B.-N, Zhang W, Lin H.-W. J. Nat. Prod. 2016; 79: 406
• 4 Gui Y.-H, Jiao W.-H, Zhou M, Zhang Y, Zeng D.-Q, Zhu H.-R, Liu K.-C, Sun F, Chen H.-F, Lin H.-W. Org. Lett. 2019; 21: 767
• 5 Jiao W.-H, Xu Q.-H, Cui J, Shang R.-Y, Zhang Y, Sun J.-B, Yang Q, Liu K.-C, Lin H.-W. Org. Chem. Front. 2020; 7: 368
• 6 Haque MA, Jana CK. Chem. Eur. J. 2017; 23: 13300
• 7 Yin X, Mato M, Echavarren AM. Angew. Chem. Int. Ed. 2017; 56: 14591
• 8 Zuo Z, Wang J, Liu J, Wang Y, Luan X. Angew. Chem. Int. Ed. 2020; 59: 653
• 9a De Rosa S, Minale L, Riccio R, Sodano G. J. Chem. Soc., Perkin Trans. 1 1976; 1408
• 9b Minale L, Riccio R, Sodano G. Tetrahedron Lett. 1974; 15: 3401
• 10 Iguchi K, Sahashi A, Kohno J, Yamada Y. Chem. Pharm. Bull. 1990; 38: 1121
• 11 Chong C, Zhang Q, Ke J, Zhang H, Yang X, Wang B, Ding W, Lu Z. Angew. Chem. Int. Ed. 2021; 61: 13807 ; Angew. Chem. 2021, 133, 13926
• 12a Beadham I, Micklefield J. Curr. Org. Synth. 2005; 2: 231
• 12b Wittig G, Geissler G. Justus Liebigs Ann. Chem. 1953; 580: 44
• 13a van Staden LF, Gravestock D, Ager DJ. Chem. Soc. Rev. 2002; 31: 195
• 13b Peterson DJ. J. Org. Chem. 1968; 33: 780
• 14a Hartley RC, McKiernan GJ. J. Chem. Soc., Perkin Trans. 1 2002; 2763
• 14b Tebbe FN, Parshall GW, Reddy GS. J. Am. Chem. Soc. 1978; 100: 3611
• 15a Julia M, Paris J.-M. Tetrahedron Lett. 1973; 14: 4833
• 15b Blakemore PR. J. Chem. Soc., Perkin Trans. 1 2002; 2563
• 16a Sun Y, Chen P, Zhang D, Baunach M, Hertweck C, Li A. Angew. Chem. Int. Ed. 2014; 53: 9012
• 16b Chou Y.-Y, Liao C.-C. Org. Lett. 2013; 15: 1584
• 16c Kawano H, Itoh M, Katoh T, Terashima S. Tetrahedron Lett. 1997; 38: 7769
• 16d Takai K, Hotta Y, Oshima K, Nozaki H. Bull. Chem. Soc. Jpn. 1980; 53: 1698
• 17 Yu W, Hjerrild P, Jacobsen KM, Tobiesen HN, Clemmensen L, Poulsen TB. Angew. Chem. Int. Ed. 2018; 57: 9805
• 18a Valente C, Moreira R, Guedes RC, Iley J, Jaffar M, Douglas KT. Bioorg. Med. Chem. 2007; 15: 5340
• 18b Matsuoka M, Hamano K, Kitao T. Synthesis 1984; 953
• 19a Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4442
• 19b Dounay AB, Overman LE. Chem. Rev. 2003; 103: 2945
• 19c Endo A, Yanagisawa A, Abe M, Tohma S, Kan T, Fukuyama T. J. Am. Chem. Soc. 2002; 124: 6552
• 19d Govek SP, Overman LE. J. Am. Chem. Soc. 2001; 123: 9468
• 19e Overman LE. Pure Appl. Chem. 1994; 66: 1423
• 19f Hong CY, Kado N, Overman LE. J. Am. Chem. Soc. 1993; 115: 11028
• 20a Solé D, Vallverdú L, Solans X, Font-Bardía M, Bonjoch J. J. Am. Chem. Soc. 2003; 125: 1587
• 20b Quan LG, Lamrani M, Yamamoto Y. J. Am. Chem. Soc. 2000; 122: 4827
• 20c Vicente J, Abad J.-A, Gil-Rubio J. J. Organomet. Chem. 1992; 436: C9
• 21 Zhang H, Ma S, Yuan Z, Chen P, Xie X, Wang X, She X. Org. Lett. 2017; 19: 3478
• 22 Baars J, Grimm I, Blunk D, Neudörfl J.-M, Schmalz H.-G. Angew. Chem. Int. Ed. 2021; 61: 14915 ; Angew. Chem. 2021, 133, 15042