A Concise Total Synthesis of Steroid Scaffolds via a Palladium-Catalyzed Dearomatization Cyclization

Zhangwei Huang; Xianhua Pan; Lei Guo; Wenjun Tang

doi:10.1055/s-0042-1751356

Synlett, Table of Contents

Synlett 2022; 33(17): 1770-1774
DOI: 10.1055/s-0042-1751356

letter

A Concise Total Synthesis of Steroid Scaffolds via a Palladium-Catalyzed Dearomatization Cyclization

Authors

Zhangwei Huang

^aSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, 201418, P. R. of China
Xianhua Pan

^aSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, 201418, P. R. of China
Lei Guo ∗

^aSchool of Perfume and Aroma Technology, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, 201418, P. R. of China
Wenjun Tang ∗

^bState Key Laboratory of Bio-Organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Shanghai 200032, P. R. of China

Abstract

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Abstract

A concise total synthesis to generate synthetically challenging steroids scaffolds is reported utilizing palladium-catalyzed dearomatization cyclization for the key cyclization step, enabling the divergent synthesis of 6,6,6,5-tetracyclic steroids cores through both ligand and reaction condition control. We have started from the simple starting materials 2,4,6-trihydroxybenzoic acid and 2-methylcyclopentane-1,3-dione to selectively generate complex steroid scaffolds in a 12-step operation.

Key words

total synthesis - steroids scaffolds - palladium catalysis - dearomatization cyclization - 6,6,6,5-tetracyclic steroids

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References

References and Notes

1a Wender PA, Verma VA, Paxton TJ, Pillow TH. Acc. Chem. Res. 2008; 41: 40
1b Szpilman AM, Carreira EM. Angew. Chem. Int. Ed. 2010; 49: 9592
1c Harvey AL, Edrada-Ebel R, Quinn RJ. Nat. Rev. Drug Discovery 2015; 14: 111
1d Allred TK, Manoni F, Harran PG. Chem. Rev. 2017; 117: 11994

2a Nesher M, Shpolansky U, Rosen H, Lichtstein D. Life Sci. 2007; 80: 2093
2b Schoner W, Scheiner-Bobis G. Am. J. Physiol.: Cell Physiol. 2007; 293: C509
2c Prassas I, Diamandis EP. Nat. Rev. Drug Discovery 2008; 7: 926
2d Bagrov AY, Shapiro JI, Fedorova OV. Pharmacol. Rev. 2009; 61: 9

3 Gao H, Popescu R, Kopp B, Wang Z. Nat. Prod. Rep. 2011; 28: 953

4a Gonzales JM, Barden CJ, Brown ST, Schleyer P. vR, Schaefer HF, Li Q.-S. J. Am. Chem. Soc. 2003; 125: 1064
4b Danda A, Kesava-Reddy N, Golz C, Strohmann C, Kumar K. Org. Lett. 2016; 18: 2632
4c Paul A, Vasseur C, Daniel SD, Seidel D. Org. Lett. 2022; 24: 1224

5 Woodward RB. J. Am. Chem. Soc. 1940; 62: 1208

6a Mukai K, Kasuya S, Nakagawa Y, Urabe D, Inoue M. Chem. Sci. 2015; 6: 3383
6b Urabe D, Nakagawa Y, Mukai K, Fukushima K.-i, Aoki N, Itoh H, Nagatomo M, Inoue M. J. Org. Chem. 2018; 83: 13888
6c Wang GQ, Chen GD, Qin SY, Hu D, Awakawa T, Li SY, Lv JM, Wang CX, Yao XS, Abe I, Gao H. Nat. Commun. 2018; 9: 1838

7 Reddy MS, Zhang H, Phoenix S. Chem. Asian J. 2009; 4: 725
8 Khatri HR, Bhattarai B, Kaplan W, Li Z, Curtis Long MJ, Aye Y, Nagorny P. J. Am. Chem. Soc. 2019; 141: 4849

9a Cao Z, Du K, Liu J, Tang W. Tetrahedron 2016; 72: 1782
9b Shao W, You S.-L. Chem. Eur. J. 2017; 23: 12489
9c Saito E, Matsumoto Y, Nakamura A, Namera Y, Nakada M. Org. Lett. 2018; 20: 692
9d Guo Z, Wang Z, Tang Y. Org. Lett. 2018; 20: 1819
9e Mu X, Yu H, Peng H, Xiong W, Wu T, Tang W. Angew. Chem. Int. Ed. 2020; 59: 8143
9f Yao T, Xia T, Yan W, Xu H, Zhang F, Xiao Y, Zhang J, Liu L. Org. Lett. 2020; 22: 4511
9g Cheng Y.-Z, Huang X.-L, Zhuang W.-H, Zhao Q.-R, Zhang X, Mei T.-S, You S.-L. Angew. Chem. Int. Ed. 2020; 59: 18062
9h Ban Y.-L, You L, Wang T, Wu L.-Z, Liu Q. ACS Catal. 2021; 11: 5054
9i Kumar R, Singh FV, Takenaga N, Dohi T. Chem. Asian J. 2022; 17: e202101115

10a Hog DT, Huber FM. E, Jiménez-Osés G, Mayer P, Houk KN, Trauner D. Chem. Eur. J. 2015; 21: 13646
10b Indu S, Telore RD, Kaliappan KP. Org. Biomol. Chem. 2020; 18: 2432

11 Fang X, Gao S, Wu Z, Yao H, Lin A. Org. Chem. Front. 2017; 4: 292
12 Cheng Q, Xie J.-H, Weng Y.-C, You S.-L. Angew. Chem. Int. Ed. 2019; 58: 5739
13 Wu X.-X, Tian H, Wang Y, Liu A, Chen H, Fan Z, Li X, Chen S. Org. Chem. Front. 2018; 5: 3310

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