Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2021; 32(07): 693-696
DOI: 10.1055/a-1303-9935
DOI: 10.1055/a-1303-9935
letter
A Concise Enantiodivergent Synthesis of Equol
This work was supported by the Japan Society for the Promotion of Science (JSPS KAKENHI, Grant Number JP17K07776) to S.T.
Abstract
Equol, a nonsteroidal estrogen produced from the metabolism of the isoflavonoid phytoestrogen daidzein, has been synthesized as both enantioenriched forms based on MacMillan’s α-arylation of carbonyl compound mediated by amino acid derived indazolidinones and copper precatalysts. The natural form of (S)-equol and its enantiomer (R)-equol have been synthesized in 8 steps from 2,4-dimethoxybenzaldehyde with good enantiomeric purity (90% ee and 90% ee, respectively).
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1303-9935.
- Supporting Information
Publication History
Received: 14 October 2020
Accepted after revision: 04 November 2020
Accepted Manuscript online:
04 November 2020
Article published online:
08 December 2020
© 2020. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References and Notes
- 1a Mayo B, Vázquez L, Flórez AB. Nutrients 2019; 11: 2231
- 1b Li B.-J. J. Food Process. Pres. 2019; 43: e14205
- 1c Sekikawa A, Ihara M, Lopez O, Kakuta C, Lopresti B, Higashiyama A, Aizenstein H, Chang Y.-F, Mathis C, Miyamoto Y, Kuller L, Cui C. Curr. Cardiol. Rev. 2019; 15: 114
- 1d Lephart ED. Cosmetics 2018; 5: 16/1
- 2a Gao L, Wang K.-x, Zhang N.-n, Li J.-q, Qin X.-m, Wang X.-l. J. Proteome Res. 2018; 17: 1833
- 2b Lee P.-G, Kim J, Kim E.-J, Lee S.-H, Choi K.-Y, Kazlauskas RJ, Kim B.-G. ACS Chem. Biol. 2017; 12: 2883
- 3a Miller RW, Kleiman R, Powell RG. J. Nat. Prod. 1988; 51: 328
- 3b Peng F, Zhu H, Meng C.-W, Ren Y.-R, Dai O, Xiong L. Molecules 2019; 24: 3218
- 4a Piccinelli AL, Fernandez MC, Rastrelli L. J. Agric. Food Chem. 2005; 53: 9010
- 4b Franchin M, Cólon DF, Castanheira FV. S, da Cunha MG, Bueno-Silva B, Alencar SM, Cunha TM, Rosalen PL. J. Nat. Prod. 2016; 79: 954
- 5 Marrian GF, Haslewood GA. Biochem. J. 1932; 26: 1227
- 6 Setchell KD, Clerici C. J. Nutr. 2010; 140: 1355
- 7 Setchell KD, Borriello SP, Hulme P, Kirk DN, Axelson M. Am. J. Clin. Nutr. 1984; 40: 569
- 8 Lephart ED. Pharm. Biol. 2013; 51: 1393
- 9 Jou H.-J, Wu S.-C, Chang F.-W, Ling P.-Y, Chu K.-S, Wu W.-H. Gynecol. Obstet. 2008; 102: 44
- 10 Caruso S, Cianci S, Fava V, Rapisarda AM. C, Cutello S, Cianci A. Menopause 2018; 25: 430
- 11 Muthyala RS, Ju YH, Sheng S, Williams LD, Doerge DR, Katzenellenbogen BS, Helferich WG, Katzenellenbogen JA. Bioorg. Med. Chem. 2004; 12: 1559
- 12a Li S.-R, Chen P.-Y, Chen L.-Y, Lo Y.-F, Tsai I.-L, Wang E.-C. Tetrahedron Lett. 2009; 50: 2121
- 12b Gupta A, Ray S. Synthesis 2008; 3783
- 12c Gharpure SJ, Sathiyanarayanan AM, Jonnalagadda P. Tetrahedron Lett. 2008; 49: 2974
- 12d Lamberton JA, Suares H, Watson KG. Aust. J. Chem. 1978; 31: 455
- 13a Kessberg A, Luebken T, Metz P. Org. Lett. 2018; 20: 3006
- 13b Umeda M, Sakamoto K, Nagai T, Nagamoto M, Ebe Y, Nishimura T. Chem. Commun. 2019; 55: 11876
- 13c Zhang H.-H, Zhao J.-J, Yu S. J. Am. Chem. Soc. 2018; 140: 16914
- 13d Zhang J, Zhang S, Yang H, Zhou D, Yu X, Wang W, Xie H. Tetrahedron Lett. 2018; 59: 2407
- 13e Yalamanchili C, Chittiboyina AG, Rotte SC. K, Katzenellenbogen JA, Helferich WG, Khan IA. Tetrahedron 2018; 74: 2020
- 13f Xia J, Nie Y, Yang G, Liu Y, Zhang W. Org. Lett. 2017; 19: 4884
- 13g Nakamura K, Ohmori K, Suzuki K. Chem. Commun. 2015; 51: 7012
- 13h Lee J.-W, List B. J. Am. Chem. Soc. 2012; 134: 18245
- 13i Yang S, Zhu S.-F, Zhang C.-M, Song S, Yu Y.-B, Li S, Zhou Q.-L. Tetrahedron 2012; 68: 5172
- 13j Takashima Y, Kaneko Y, Kobayashi Y. Tetrahedron 2010; 66: 197
- 13k Heemstra JM, Kerrigan SA, Doerge DR, Helferich WG, Boulanger WA. Org. Lett. 2006; 8: 5441
- 13l Qin T, Metz P. Org. Lett. 2017; 19: 2981
- 14a Saraf MK, Jeng Y.-J, Watson CS. Steroids. in press DOI: 10.1016/j.steroids.2019.01.008.
- 14b Lephart ED. Int. J. Mol. Sci. 2017; 18: 1193/1
- 15a Bielawski M, Olofsson B. Chem. Commun. 2007; 24: 2521
- 15b Zhu M, Jalalian N, Olofsson B. Synlett 2008; 592
- 16a Conrad JC, Kong J, Laforteza BN, MacMillan DW. C. J. Am. Chem. Soc. 2009; 131: 11640
- 16b Allen AE, MacMillan DW. C. J. Am. Chem. Soc. 2011; 133: 4260
- 17 General Procedure for the Synthesis of (S)-3-(2,4-Dimethoxyphenyl)-2-(4-methoxyphenyl)propan-1-ol (9)16a To an oven-dried round-bottom flask was added crude diaryliodonium salt 4 (65–70% purity determined by 1H NMR; 3.24 g, 4.34 mmol) and CuBr (122 mg, 0.85 mmol), and then toluene (6.4 mL) and Et2O (3.2 mL) were added. Afterwards, (2R,5R)-5 (334 mg, 0.844 mmol) and NaHCO3 (1.62 g, 19.3 mmol) were added to the suspension. Under argon atmosphere, a solution of aldehyde 3 (823 mg) in toluene/Et2O (2:1, 4.8 mL) was added. The reaction mixture was stirred at room temperature for 44 h. The resulting mixture was diluted with CH2Cl2 (10 mL) and cooled to –23 °C. After adding NaBH4 (1.64 g, 43.3 mmol), cold MeOH (8 mL) was gradually added to the solution, and the mixture was stirred for 1 h at –23 °C. The reaction mixture was quenched with water (8 mL) and extracted with EtOAc (3 × 30 mL). The combined organic layer was washed with sat. NH4Cl aq. (2 × 30 mL), dried over Na2SO4, and the solvent was removed in vacuo. The resulting yellow oil was purified by silica gel column chromatography using hexane/EtOAc (7:3) as an eluent to give (S)-3-(2,4-dimethoxyphenyl)-2-(4-methoxyphenyl)propan-1-ol (9) including inseparable 3-(2,4-dimethoxyphenyl)propyl alcohol (8) as a pale yellow oil (630 mg, (S)-9/8 = 71:29 estimated by 1H NMR analysis).