Synthesis 2024; 56(10): 1585-1592
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
,
This work was funded by the Université Paris-Saclay, Centre National de la Recherche Scientifique (CNRS), China Scholarship Council (PhD fellowship for G.H.) and LabEx CHARM
3 AT (postdoctoral fellowship for L.P.). The authors thank the funding organizations for support.
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
Supporting Information
Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751529.
Supporting Information
Publication History
Received: 21 August 2023
© 2023. Thieme. All rights reserved
Georg Thieme Verlag KG
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
