Recent Progress in the Total Synthesis of abeo-Steroids

doi:10.6023/cjoc202506022

Abstract

Research on steroids play a significant role in organic chemistry, medicinal chemistry of natural products, and drug discovery. To date, more than 100 steroidal drugs have been approved by U.S. Food and Drug Administration (FDA) for the treatment of cancer, inflammation, pain, and heart failure. Recently, more and more abeo-steroids have been isolated. Due to their novel structures and important biological activities, abeo-steroids have attracted considerable attention from the synthetic community. In general, abeo-steroids are complex and diverse, containing a medium ring (seven-membered ring) or bridged ring system and possessing multiple stereogenic centers. All these structural features present considerable synthetic challenges. The latest progress in the total synthesis of abeo-steroids in the past eight years is summarized, focusing on the innovative synthetic strategies and methods. Finally, a brief outlook for the future development of abeo-steroids and related field is discussed.

Key words: steroid, abeo-steroid, total synthesis, seven-membered ring, bridged ring system

Cite this article

Lilin Zhao, Zhaoqi Li, Liping Zhong, Long Min. Recent Progress in the Total Synthesis of abeo-Steroids[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 21-38.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 24

Figure 1. Selected FDA approved steroidal drugs (A) and selected abeo-steroids (B)

Figure 2. Structures of cyclocitrinol and selected members of cyclocitrinols

Scheme 1. Li’s asymmetric total synthesis of cyclocitrinol

Scheme 2. Gui’s ten-step synthesis of cyclocitrinol

Scheme 3. Gui’s unified synthesis of other nine cyclocitrinols

Figure 3. Structures of pleurocins A and B

Scheme 4. Heretsch’s asymmetric synthesis of pleurocin A (matsutakone) and pleurocin B

Figure 4. Structures of swinhoeisterol A, dankasterone A, dankasterone B and periconiastone A

Scheme 5. Heretsch’s asymmetric synthesis of swinhoeisterol A, dankasterone A, dankasterone B and periconiastone A

Scheme 6. Ma’s asymmetric total synthesis of dankasterone A, dankasterone B and periconiastone A

Scheme 7. Gui’s asymmetric total synthesis of swinhoeisterols A~C

Figure 5. Structure of bufospirostenin A

Scheme 8. Li’s asymmetric total synthesis of bufospirostenin A

Scheme 9. Gui’s asymmetric synthesis of bufospirostenin A

Scheme 10. Gui’s asymmetric synthesis of ophiopogonol A

Scheme 11. Yang’s asymmetric synthesis of bufospirostenin A

Figure 6. Structure of phomarol

Scheme 12. Li’s asymmetric total synthesis of phomarol

Scheme 13. Gui’s asymmetric total synthesis of phomarol

Figure 7. Structures of bufogargarizins A and B

Scheme 14. Li’s asymmetric total synthesis of bufogargarizin A

Scheme 15. Li’s asymmetric total synthesis of bufogargarizin B

Figure 8. Structure of aspersteroid A

Scheme 16. Gui’s asymmetric synthesis of aspersteroid A

References 47

[1]	Lednicer D. Steroid Chemistry at a Glance, John Wiley & Sons, Chichester, West Sussex, U.K. 2011.
[2]	Noack F.; Heinze R. C.; Heretsch P. Synthesis 2019, 51, 2039. doi: 10.1055/s-0037-1611576
[3]	Kim W. S.; Du K.; Esatman A.; Hughes R. P.; Micalizio G. C. Nat. Chem. 2018, 10, 70. doi: 10.1038/nchem.2865
[4]	Biellmann J.-F. Chem. Rev. 2003, 103, 2019. doi: 10.1021/cr020071b
[5]	Chapelin A.-S.; Moraléda D.; Rodriguez R.; Ollivier C.; Santelli M. Tetrahedron 2007, 63, 11511. doi: 10.1016/j.tet.2007.08.087
[6]	Khatri H. R.; Carney N.; Rutkoski R.; Bhattarai B.; Nagorny P. Eur. J. Org. Chem. 2020, 2020, 755. pmid: 32601521
[7]	Min L.; Zhong L.-P.; Li C.-C. Acc. Chem. Res. 2023, 56, 2378. doi: 10.1021/acs.accounts.3c00350
[8]	Wang Y.; Gui J. Acc. Chem. Res. 2024, 57, 568. doi: 10.1021/acs.accounts.3c00716
[9]	Liu J.; Wu J.; Fan J.-H.; Yan X.; Mei G.; Li C.-C. J. Am. Chem. Soc. 2018, 140, 5365. doi: 10.1021/jacs.8b02629
[10]	Lu Z.; Zhang X.; Guo Z.; Chen Y.; Mu T.; Li A. J. Am. Chem. Soc. 2018, 140, 9211. doi: 10.1021/jacs.8b05070
[11]	Li X.; Zhang Z.; Fan H.; Miao Y.; Tian H.; Gu Y.; Gui J. J. Am. Chem. Soc. 2021, 143, 4886. doi: 10.1021/jacs.0c13426
[12]	Ning Y.; Tian H.; Gui J. Angew. Chem., Int. Ed. 2021, 60, 11222. doi: 10.1002/anie.v60.20
[13]	Ning Y.; Wang Y.; Gui J. JACS Au. 2024, 4, 635. doi: 10.1021/jacsau.3c00698 pmid: 38425898
[14]	Alekseychuk M.; Heretsch P. J. Am. Chem. Soc. 2022, 144, 21867. doi: 10.1021/jacs.2c10735 pmid: 36410736
[15]	Kozlovsky A. G.; Zhelifonova V. P.; Ozerskaya S. M.; Vinokurova N. G.; Adanin V. M.; Gräfe U. Pharmazie 2000, 55, 470. pmid: 10907264
[16]	Amagata T.; Amagata A.; Tenney K.; Valeriote F. A.; Lobkovsky E.; Clardy J.; Crews P. Org. Lett. 2003, 5, 4393. pmid: 14602008
[17]	Yu F. X.; Li Z.; Chen Y.; Yang Y. H.; Li G. H.; Zhao P. J. Fitoterapia 2017, 117, 41. doi: 10.1016/j.fitote.2016.12.012
[18]	El Sheikh S.; Greffen A. M. Z.; Lex J.; Neudorfl J. M.; Schmalz H. G. Synlett 2007, 12, 1881.
[19]	Plummer C. W.; Wei C. S.; Yozwiak C. E.; Soheili A.; Smithback S. O.; Leighton J. L. J. Am. Chem. Soc. 2014, 136, 9878. doi: 10.1021/ja505131v
[20]	Mei G.; Liu X.; Qiao C.; Chen W.; Li C.-C. Angew. Chem., Int. Ed. 2015, 54, 1754. doi: 10.1002/anie.v54.6
[21]	Min L.; Liu X.; Li C.-C. Acc. Chem. Res. 2020, 53, 703. doi: 10.1021/acs.accounts.9b00640
[22]	Wang Y.; Ju W.; Tian H.; Tian W.; Gui J. J. Am. Chem. Soc. 2018, 140, 9413. doi: 10.1021/jacs.8b06444 pmid: 30008202
[23]	Wang Y.; Ju W.; Tian H.; Sun S.; Li X.; Tian W.; Gui J. J. Am. Chem. Soc. 2019, 141, 5021. doi: 10.1021/jacs.9b00925 pmid: 30827095
[24]	Heinze R. C.; Heretsch P. J. Am. Chem. Soc. 2019, 141, 1222. doi: 10.1021/jacs.8b13356
[25]	Zhao Z.-Z.; Chen H.-P.; Wu B.; Zhang L.; Li Z.-H.; Feng T.; Liu J.-K. J. Org. Chem. 2017, 82, 7974. doi: 10.1021/acs.joc.7b01230
[26]	Kikuchi T.; Horii Y.; Maekawa Y.; Masumoto Y.; In Y.; Tomoo K.; Sato H.; Yamano A.; Yamada T.; Tanaka R. J. Org. Chem. 2017, 82, 10611. doi: 10.1021/acs.joc.7b01259
[27]	Duecker F. L.; Heinze R. C.; Heretsch P. J. Am. Chem. Soc. 2020, 142, 104. doi: 10.1021/jacs.9b12899 pmid: 31870147
[28]	Gong J.; Sun P.; Jiang N.; Riccio R.; Lauro G.; Bifulco G.; Li T.-J.; Gerwick W. H.; Zhang W. Org. Lett. 2014, 16, 2224. doi: 10.1021/ol5007345 pmid: 24694058
[29]	Amagata T.; Doi M.; Tohgo M.; Minoura K.; Numata A. Chem. Commun. 1999, 1321.
[30]	Amagata T.; Tanaka M.; Yamada T.; Doi M.; Minoura K.; Ohishi H.; Yamori T.; Numata A. J. Nat. Prod. 2007, 70, 1731. pmid: 17988094
[31]	Gao W.; Chai C.; He Y.; Li F.; Hao X.; Cao F.; Gu L.; Liu J.; Hu Z.; Zhang Y. Org. Lett. 2019, 21, 8469. doi: 10.1021/acs.orglett.9b03270
[32]	Chen P.; Wang C.; Yang R.; Xu H.; Wu J.; Jiang H.; Chen K.; Ma Z. Angew. Chem., Int. Ed. 2021, 60, 5512. doi: 10.1002/anie.v60.10
[33]	Huang G.; Zhang X.; Gu Y.-C.; Gui J. J. Am. Chem. Soc. 2025, 147, 20239. doi: 10.1021/jacs.5c07053
[34]	Cheng M.-J.; Zhong L.-P.; Gu C.-C.; Zhu X.-J.; Chen B.; Liu J.-S.; Wang L.; Ye W.-C.; Li C.-C. J. Am. Chem. Soc. 2020, 142, 12602. doi: 10.1021/jacs.0c05479
[35]	Wang Y.; Tian H.; Gui J. J. Am. Chem. Soc. 2021, 143, 19576. doi: 10.1021/jacs.1c10067 pmid: 34762408
[36]	Yang P.; Li Y.-Y.; Tian H.; Qian G.-L.; Wang Y.; Hong X.; Gui J. J. Am. Chem. Soc. 2022, 144, 17769. doi: 10.1021/jacs.2c07944
[37]	Liu B.; Li B.; Chen G.; Pan Y.; Zhou D.; Li N. Phytochemistry 2022, 193, 112975. doi: 10.1016/j.phytochem.2021.112975
[38]	Huang J.; Cao T.; Zhang Z.; Yang Z. J. Am. Chem. Soc. 2022, 144, 2479. doi: 10.1021/jacs.1c12395 pmid: 35112846
[39]	Fan J.-H.; Wang J.-J.; Li F.; Wang G.; Guo Q.; Chung L.-W.; Li C.-C. CCS Chem. 2021, 3, 348. doi: 10.31635/ccschem.021.202000721
[40]	Kim E. L.; Li J. L.; Hong J.; Yoon W. D.; Kim S. H.; Liu Y.; Wei X.; Jung J. H. Tetrahedron Lett. 2016, 57, 2803. doi: 10.1016/j.tetlet.2016.05.050
[41]	Wang X.; Huang G.; Wang Y.; Gui J. J. Am. Chem. Soc. 2023, 145, 9354. doi: 10.1021/jacs.3c02817
[42]	Zhong L.-P.; Feng R.; Wang J.-J.; Li C.-C. J. Am. Chem. Soc. 2023, 145, 2098. doi: 10.1021/jacs.2c13494
[43]	Tian H.-Y.; Wang L.; Zhang X.-Q.; Wang Y.; Zhang D.-M.; Jiang R.-W.; Liu Z.; Liu J.-S.; Li Y.-L.; Ye W.-C. Chem.-Eur. J. 2010, 16, 10989. doi: 10.1002/chem.v16:36
[44]	Cen K.; Bao J.; Wang X.; Tian H.; Wang Y.; Gui J. J. Am. Chem. Soc. 2024, 146, 6481. doi: 10.1021/jacs.4c01016
[45]	Liu L.; Duan F.-F.; Gao Y.; Peng X.-G.; Chang J.-L.; Chen J.; Ruan H.-L. Org. Lett. 2021, 23, 9620. doi: 10.1021/acs.orglett.1c03863
[46]	Bosworth N.; Emke A.; Midgley J. M.; Moore C. J.; Whalley W. B.; Ferguson G.; Marsh W. C. J. Chem. Soc., 1977, 805.
[47]	During our submission of this manuscript, an elegant review on synthesis of steroid natural products by Gui and co-workers was just published online, see: Wang, Y.; Gui, J. Chem. Soc. Rev. 2025, 54, 6807. doi: 10.1039/d3cs01150j pmid: 40497439

abeo-甾体的全合成研究进展