Total Synthesis of Lucidumone: Attempted Shortcuts, Dead Ends and Lessons Learnt

Guangho Huang; Amaury Laporte; Lucas Pagès; Cyrille Kouklovsky; Aurélien de la Torre

doi:10.1055/s-0042-1751529

Synthesis, Table of Contents

Synthesis 2024; 56(10): 1585-1592
DOI: 10.1055/s-0042-1751529

paper

Bürgenstock Special Section 2023 – Future Stars in Organic Chemistry

Total Synthesis of Lucidumone: Attempted Shortcuts, Dead Ends and Lessons Learnt

Guangho Huang

,

Amaury Laporte

,

Lucas Pagès

,

Cyrille Kouklovsky

,

Aurélien de la Torre ∗

Abstract

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Abstract

Lucidumone is a meroterpenoid isolated from the mushroom Ganoderma lucidum, displaying selective COX-2 inhibitory activity. In this work, we detail our synthetic efforts which led to the first enantioselective synthesis of lucidumone in 13 steps (longest linear sequence). Beyond the key retro-[4+2]/intramolecular Diels–Alder cascade, we discuss the difficulties regarding fragment assembly, introduction of the methyl ketone moiety and choice of adequate protecting group.

Key words

total synthesis - natural products - cycloaddition - pyrones - enantioselectivity

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References

References
1 Current address: G. Huang, Max-Planck-Institut für Kohlenforschung, 45470 Mülheim an der Ruhr, Germany.
2 Yan Y.-M, Zhang H.-X, Liu H, Wang Y, Wu J.-B, Li Y.-P, Cheng Y.-X. Org. Lett. 2019; 21: 8523
3 Wachtel-Galor S, Yuen J, Buswell JA, Benzie IF. F. In Herbal Medicine: Biomolecular and Clinical Aspects, 2nd ed. Benzie IF. F, Wachtel-Galor S. CRC Press/Taylor & Francis; Boca Raton: 2011. Chap. 9

4a Flower RJ. Nat. Rev. Drug Discovery 2003; 2: 179
4b Dieppe PA, Ebrahim S, Martin RM, Jüni P. BMJ 2004; 329: 867

5a Huang G, Kouklovsky C, de la Torre A. J. Am. Chem. Soc. 2022; 144: 17803
5b Huang G, Kouklovsky C, de la Torre A. Synlett 2023; 34: 1195

6a Ma S, Li Z, Yu P, Shi H, Yang H, Yi J, Zhang Z, Duan X, Xie X, She X. Org. Lett. 2022; 24: 5541
6b Kawamoto Y, Noguchi N, Kobayashi T, Ito H. Angew. Chem. Int. Ed. 2023; 62: e202304132

7 Huang G, Guillot R, Kouklovsky C, Maryasin B, de la Torre A. Angew. Chem. Int. Ed. 2022; 61: e202208185
8 Khalil K, Al-Matar H, Elnagdi M. Eur. J. Chem. 2010; 1: 252

9a Sahoo D, Sarkar S, Jana S. Tetrahedron Lett. 2019; 60: 151084
9b Murata R, Hirano K, Uchiyama M. Chem. Asian J. 2015; 10: 1286
9c Genna DT, Posner GH. Org. Lett. 2011; 13: 5358

10a Dieter RK. Tetrahedron 1999; 55: 4177
10b Pandey AK. ChemCatChem 2022; 14: e202101982
10c Milstein D, Stille JK. J. Am. Chem. Soc. 1978; 100: 3636
10d Milstein D, Stille JK. J. Org. Chem. 1979; 44: 1613
10e Cason J, Kraus KW. J. Org. Chem. 1961; 26: 1768
10f Grey RA. J. Org. Chem. 1984; 49: 2288

11 Fier PS, Roberts RA, Larson RT. Org. Lett. 2023; 25: 3131

12a Dochain S, Vetica F, Puttreddy R, Rissanen K, Enders D. Angew. Chem. Int. Ed. 2016; 55: 16153
12b Tellam JP, Kociok-Köhn G, Carbery DR. Org. Lett. 2008; 10: 5199

13a Murata T, Kuboki T, Ishikawa R, Saito T, Taguchi S, Takeuchi K, Hatano E, Shimonaka M, Shiina I. J. Nat. Prod. 2018; 81: 2364
13b Wang S, Kraus GA. Synlett 2019; 30: 353
13c Buckle DR, Morgan NJ, Ross JW, Smith H, Spicer BA. J. Med. Chem. 1973; 16: 1334

14 Tsukamoto H, Nomura Y, Doi T. Heterocycles 2019; 99: 549

15a Wolter M, Nordmann G, Job GE, Buchwald SL. Org. Lett. 2002; 4: 973
15b Altman RA, Shafir A, Choi A, Lichtor PA, Buchwald SL. J. Org. Chem. 2008; 73: 284

16 Grabovyi GA, Bhatti A, Mohr JT. Org. Lett. 2020; 22: 4196
17 Tokuyama H, Yokoshima S, Yamashita T, Fukuyama T. Tetrahedron Lett. 1998; 39: 3189

18a Bechara WS, Pelletier G, Charette AB. Nat. Chem. 2012; 4: 228
18b Kaiser D, Bauer A, Lemmerer M, Maulide N. Chem. Soc. Rev. 2018; 47: 7899

19 For a similar way to mask cyclopentadienes using norbornadienes, see: Fadel M, Carreira EM. J. Am. Chem. Soc. 2023; 145: 8332

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