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Synlett 2023; 34(19): 2257-2261
DOI: 10.1055/a-2103-9925
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The Total Synthesis of Mollanol A by a Convergent Strategy

Ming Yang  ∗
Financial Support was provided by the Major Project of the Department of Science and Technology of Gansu Province (22ZD6FA006), National Natural Science Foundation of China (21901094 and 22071089), and Lanzhou University
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Abstract

Here, we briefly highlight our 15-step total synthesis of mollanol A, the first isolated member of the mollane-type grayanoids, which relied on a convergent strategy. A Stille coupling and a vinylogous aldol reaction/intramolecular oxa-Michael addition sequence were used to assemble the two fragments that featured most of the important chiral centers and nearly all the essential oxidation states of the natural product. The bicyclo[3.2.1]octane fragment was synthesized by using an InCl3-catalyzed Conia–ene cyclization reaction. The challenging tetrasubstituted alkene was constructed through a 1,4-reduction of the conjugated alkenes at a late stage.

1 Introduction

2 Total Synthesis of Mollanol A

3 Conclusion

Key words

grayanoids - total synthesis - mollanol A - convergent synthesis - Conia–ene cyclization - intramolecular oxa-Michael addition


Publication History

Received: 22 May 2023

Accepted after revision: 31 May 2023

Accepted Manuscript online:
31 May 2023

Article published online:
10 July 2023

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  • References

    • 1a Wang L, Qin G. Tianran Chanwu Yanjiu Yu Kaifa 1997; 9: 82
    • 1b Li Y, Liu Y.-B, Yu S.-S. Phytochem. Rev. 2013; 12: 305
      Crossref
    • 1c Li C.-H, Yan X.-T, Zhang A.-L, Gao J.-M. J. Agric. Food Chem. 2017; 65: 9934
      CrossrefPubMed
    • 1d Li C.-H, Zhang J.-Y, Zhang X.-Y, Li S.-H, Gao J.-M. Eur. J. Med. Chem. 2019; 166: 400
      CrossrefPubMed
    • 2a Hamanaka N, Matsumoto T. Tetrahedron Lett. 1972; 13: 3087
      Crossref
    • 2b Gasa S, Hamanaka N, Matsunaga S, Okuno T, Takeda N, Matsumoto T. Tetrahedron Lett. 1976; 17: 553
      Crossref
  • 3 Kan T, Hosokawa S, Nara S, Oikawa M, Ito S, Matsuda F, Shirahama H. J. Org. Chem. 1994; 59: 5532
    CrossrefPubMed
  • 4 Turlik A, Chen Y, Scruse AC, Newhouse TR. J. Am. Chem. Soc. 2019; 141: 8088
    CrossrefPubMed
    • 5a Yu K, Yang Z.-N, Liu C.-H, Wu S.-Q, Hong X, Zhao X.-L, Ding H. Angew. Chem. Int. Ed. 2019; 58: 8556
      CrossrefPubMed
    • 5b Gao J, Rao P, Xu K, Wang S, Wu Y, He C, Ding H. J. Am. Chem. Soc. 2020; 142: 4592
      CrossrefPubMed
    • 5c Zhu A, Lyu Y, Xia Q, Wu Y, Tang D, He C, Zheng G, Feng Y, Wang Y, Yao G, Ding H. J. Am. Chem. Soc. 2023; 145: 8540
      CrossrefPubMed
    • 6a Kong L, Yu H, Deng M, Wu F, Jiang Z, Luo T. J. Am. Chem. Soc. 2022; 144: 5268
      CrossrefPubMed
    • 6b Kong L, Yu H, Deng M, Wu F, Chen S.-C, Luo T. J. Org. Chem. 2023; 88: 6017
      CrossrefPubMed
  • 7 Wang Y, Zhao R, Yang M. J. Am. Chem. Soc. 2022; 144: 15033
    CrossrefPubMed
  • 8 Ma T, Cheng H, Pitchakuntla M, Ma W, Jia Y. J. Am. Chem. Soc. 2022; 144: 20196
    CrossrefPubMed
  • 9 Li Y, Liu Y.-B, Liu Y.-L, Wang C, Wu L.-Q, Li L, Ma S.-G, Qu J, Yu S.-S. Org. Lett. 2014; 16: 4320
    CrossrefPubMed
    • 10a Zheng G, Jin P, Huang L, Zhang Q, Meng L, Yao G. Bioorg. Chem. 2020; 99: 103794
      CrossrefPubMed
    • 10b Jin P, Zheng G, Yuan X, Ma X, Feng Y, Yao G. Bioorg. Chem. 2021; 111: 104870
      CrossrefPubMed
  • 11 Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE. S, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS. Cell 2008; 134: 743
    CrossrefPubMed
  • 12 This convergent design logic was also applied in our recent syntheses of trans-clerodanes and sesquiterpene (hydro)quinones; see: Zhu W, Yin Q, Lou Z, Yang M. Nat. Commun. 2022; 13: 6633
    CrossrefPubMed
    • 13a Yang M, Yin F, Fujino H, Snyder SA. J. Am. Chem. Soc. 2019; 141: 4515
      CrossrefPubMed
    • 13b Qu P, Snyder SA. J. Am. Chem. Soc. 2021; 143: 11951
      CrossrefPubMed
    • 13c Kennedy-Smith JJ, Staben ST, Toste FD. J. Am. Chem. Soc. 2004; 126: 4526
      CrossrefPubMed
    • 13d Barabé F, Bétournay G, Bellavance G, Barriault L. Org. Lett. 2009; 11: 4236
      CrossrefPubMed
    • 13e Huwyler N, Carreira EM. Angew. Chem. Int. Ed. 2012; 51: 13066
      CrossrefPubMed
    • 13f Hack D, Blümel M, Chauhan P, Philipps AR, Enders D. Chem. Soc. Rev. 2015; 44: 6059
      CrossrefPubMed
    • 13g Ye Q, Qu P, Snyder SA. J. Am. Chem. Soc. 2017; 139: 18428
      CrossrefPubMed
  • 14 Kawamoto Y, Karube F, Kobayashi T, Ito H. Org. Lett. 2020; 22: 7609
    CrossrefPubMed
  • 15 Enders D, Nühring A, Runsink J. Chirality 2000; 12: 374
    CrossrefPubMed
  • 16 Xie J.-H, Liu X.-Y, Yang X.-H, Xie J.-B, Wang L.-X, Zhou Q.-L. Angew. Chem. Int. Ed. 2012; 51: 201
    CrossrefPubMed
  • 17 Kharasch MS, Sosnovsky G, Yang NC. J. Am. Chem. Soc. 1959; 81: 5819
    CrossrefPubMed
  • 18 Demuth M. Helv. Chim. Acta 1978; 61: 3136
    CrossrefPubMed
  • 19 Chen Y, Zhang W, Ren L, Li J, Li A. Angew. Chem. Int. Ed. 2018; 57: 952
    CrossrefPubMed
  • 20 Sodeoka M, Shibasaki M. Synthesis 1993; 643
    Article in Thieme ConnectPubMed
  • 21 Steines S, Englert U, Drießen-Hölscher B. Chem. Commun. 2000; 217
    CrossrefPubMed
  • 22 Bauld NL. J. Am. Chem. Soc. 1962; 84: 4347
    CrossrefPubMed