Citation: Jiang Chongguo, Chen Sijia, Gong Jianxian, Yang Zhen. Synthetic Study Toward the 4,5-Spirocycle Skeleton of Phainanoids[J]. Acta Chimica Sinica, ;2020, 78(9): 928-932. doi: 10.6023/A20060198 shu

Synthetic Study Toward the 4,5-Spirocycle Skeleton of Phainanoids

Jiang Chongguo ^a,† ,
Chen Sijia ^a,† ,
Gong Jianxian ^a,c,, ,
Yang Zhen ^a,b,c,,

a.
Laboratory of Chemical Genomics, State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China
b.
College of Chemistry and Molecular Engineering of Peking University, Beijing 100871, China
c.
Shenzhen Bay Laboratory, Shenzhen 518055, China

Corresponding author: Gong Jianxian, gongjx@pku.edu.cn Yang Zhen, zyang@pku.edu.cn
Received Date: 1 June 2020
Available Online: 9 July 2020
Fund Project: Shenzhen Basic Research Program JCYJ20170818090044432Project supported by the National Basic Research Program of China 21632002Project supported by the National Basic Research Program of China (Nos. 21632002, 21772008), National Key Research and Development Project (No. 2018YFC0310905), Shenzhen Basic Research Program (No. JCYJ20170818090044432) and Funding Project of Shenzhen-Hong Kong Institute of Brain Science (No. 2019SHIBS0004).National Key Research and Development Project 2018YFC0310905Funding Project of Shenzhen-Hong Kong Institute of Brain Science 2019SHIBS0004Project supported by the National Basic Research Program of China 21772008

Figures(8)

Attempts to synthesize the 4,5-spirocycle skeleton of Phainanoids by rhodium-catalyzed arylative cyclization of alkynone 5 and the addition of Grignard reagent 9 to α-alkoxyl cyclobutone 8, followed by intramolecular S_NAr reaction are reported. Phainanoids, highly modified triterpenoids, were isolated from Phyllanthus hainanensis by Yue and co-workers. They have been found to show intriguing immunosuppressive activities. The most potent of them, Phainanoid F, inhibit the proliferation of T cells with an IC₅₀ value of (2.04±0.01) nmol/L and B cells with an IC₅₀ value <(1.60±0.01) nmol/L. The noteworthy activities and the lack of Phainanoids in nature resources make the synthesis of them for further biological evaluation a challenge for chemists. Our synthesis started from known compound 1, after Birch reduction and alkylation to give alkynone 5. The rhodium-catalyzed arylative cyclization of alkynone 5 to deliver tetrasubstituted cyclobutene 6 was performed by the following procedure. Under an atmosphere of Ar, to an oven-dried Schlenk tube with[Rh(OH)(cod)]₂ (35.5 mg, 0.078 mmol, 0.012n₅), phenylboronic acid (2.0 g, 16.3 mmol, 2.5n₅), were added a solution of ketone 5 (1.9 g, 6.5 mmol, 1.0n₅) in 1,4-dioxane (32.0 mL) and H₂O (0.3 mL) at room temperature. The mixture was stirred at 35℃ for 12 h. Another [Rh(OH)(cod)]₂ (35.5 mg, 0.078 mmol, 0.012n₅) and phenylboronic acid (2.0 g, 16.3 mmol, 2.5n₅) was added to the mixture. The mixture was stirred at 35℃ for 12 h. Subsequently, hydroxyl group was protected with ethoxymethyl (EOM) group to furnish 7, followed by ozonolysis to generate ketone 8. Ketone 8 was reacted with fresh prepared Grignard reagent 9 in Felkin-Anh modelinstead ofthe Cram's chelation-control model to deliver alcohol 10. The explanation of the diastereoselectivity of this reaction could be illustrated from two aspects:(1) the rigid structure of α-alkoxyl cyclobutone 8 increased the energy barrier for the transition state of chelation between magnesium ions and alkoxyl substituent; (2) the magnesium ions were not chelated with the alkoxyl substituent as well as the carbonyl oxygen was due to the intramolecular chelation with fluorine atom. Alcohol 10 underwent intramolecular S_NAr reaction and deprotection to deliver 4,5-spirocycle compound 18.
- Phainanoids,
- 4,5-spirocycle skeleton,
- rhodium-catalyzed arylative cyclization,
- S_NAr,
- Cram's chelation
1. [1]
  Fan, Y.-Y.; Zhang, H.; Zhou, Y.; Liu, H.-B.; Tang, W.; Zhou, B.;Zuo, J.-P.; Yue, J.-M. J. Am. Chem. Soc. 2015, 137, 138.
2. [2]
  Xie, J.; Wang, J.; Dong, G. Org. Lett. 2017, 19, 3017.
3. [3]
  Zhang, C. L.; Nan, F. J. Tetrahedron Lett. 2017, 58, 4357.
4. [4]
  Reviews:(a) Mascareñas, J. L.; Varela, I.; López, F. Acc. Chem. Res. 2019, 52, 465.(b) Kwiatkowski, M. R.; Alexanian, E. J. Acc. Chem. Res. 2019, 52, 1134.(c) Montgomery, J. Angew. Chem., Int. Ed. 2004, 43, 3890.(d) Bates, R. W.; Satcharoenb, V. Chem. Soc. Rev. 2002, 31, 12.(e) Inglesby, P. A.; Evans, P. A. Chem. Soc. Rev. 2010, 39, 2791.(f) Marinetti, A.; Jullien, H.; Voituriez, A. Chem. Soc. Rev. 2012, 41, 4884.(g) Aubert, C.; Fensterbank, L.; Garcia, P.; Malacria, M.; Simonneau, A. Chem. Rev. 2011, 111, 1954.(h) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. Rev. 1996, 96, 635.(i) Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev. 2002, 102, 813.(j) Grigg, R.; Sridharan,V. J. Organomet. Chem. 1999, 576, 65.(k) Xiao M. Y.; Zhu S.; Shen Y. B.; Wang L.; Xiao J. N. Chin. J. Org. Chem. 2018, 38, 328.(l) Li J. X.; Lin S.; Huang R. K.; Li C.; Yang S. R. Chin. J. Org. Chem. 2019, 39, 1417.(m) Geng D. G.; Chin. J. Org. Chem. 2019, 39, 301.(n) Qian X. Y.; Xiong P.; Xu H. C. Acta Chim. Sinica 2019, 77, 879.(o) Xu J.; Zhang S. F.; Luo Y.; Zhang, L.; Zhang, F.; Huang, T. J.; Song, Q. L. Acta Chim. Sinica 2019, 77, 932.(p) Liao F. M.; Du Y.; Zhou F.; Zhou J. Acta Chim. Sinica 2018, 76, 862.(q) Wang, W. G.; Huang, S.; Yan, S. K.; Sun, X. J.; Tung, C. H.; Xu, Z. H. Chin. J. Chem. 2020, 38, 445.(r) Zhou, L. J.; Xu, B.; Ji, D. T.; Zhang, Z. M.; Zhang, J. L. Chin. J. Chem. 2020, 38, 577.
5. [5]
  Miura, T.; Shimada, M.; Murakami, M. Tetrahedron 2007, 63, 6131.
6. [6]
  (a) Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81, 2748.(b) Mengel, A.; Reiser, O. Chem. Rev. 1999, 99, 1191.(c) Chen, X.; Hortelano, E. R.; Eliel, E. L. J. Am. Chem. Soc. 1990, 112, 6130.(d) Fan, X. Y.; Walsh, P. J. Acc. Chem. Res. 2017, 50, 2389.(e) Bartolo, N. D.; Read, J. A.; Valentín, E. M.; Woerpel, K. A. Chem. Rev. 2020, 120, 1513.(f) Stanton, G. R.; Koz, G.; Walsh, P. J. J. Am. Chem. Soc. 2011, 133, 7969.(g) Ye, J. L.; Huang, P. Q.; Lu, X. J. Org. Chem. 2007, 72, 35.(h) Bailey, W. F.; Reed, D. P.; Clark, D. R.; Kapur, G. N. Org. Lett. 2001, 3, 1865.
7. [7]
  Ciceri, P.; Demnitz, F. W. J. Tetrahedron Lett. 1997, 38, 389.
8. [8]
  Ali, A.; Guile, S. D.; Saxton, J. E.; Thornton-Pett, M. Tetrahedron 1991, 41, 6407.
9. [9]
  (a) Ito, Y.; Hirao, T.; Saegusa, T. J. Org. Chem. 1978, 43, 1011.(b) Toyooka, N.; Okumura, M.; Nemoto, H. J. Org. Chem. 2002, 67, 6078.
10. [10]
  Moustafa, G. A. I.; Saku, Y.; Aoyama, H.; Yoshimitsu, T. Chem. Commun. 2014, 50, 15706.
11. [11]
  Chérest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 9, 2199.
12. [12]
  Butenschn, H. Chem. Ber. 1994, 127, 137.
13. [13]
  Hegedus, L. S.; Ranslow, P. B. Synthesis 2000, 7, 953.
14. [14]
  (a) Yamazaki, T.; Ando, M.; Kitazume, T.; Kubota, T.; Omura, M. Org. Lett. 1999, 1, 905.(b) Yamazaki, T.; Kawashita, S.; Kitazume, T; Kubota, T. Chem. Eur. J. 2009, 15, 11461.(c) Tenza, K.; Northen, J. S.; O'Hagan, D.; Slawin, A. M. Z. J. Fluorine Chem. 2004, 125, 1779.(d) Sazonov, P. K.; Oprunenko, Y. F.; Khrustalev, V. N.; Beletskaya, I. P. J. Fluorine Chem. 2011, 132, 587.(e) Kulawiec, R. J.; Holt, E. M.; Lavin, M.; Crabtree, R. H. Inorg. Chem. 1987, 26, 2559.(f) Ooi, T.; Kagoshima, N.; Maruoka, K. J. Am. Chem. Soc. 1997, 119, 5754.(g) Kawachi, A.; Tani, A.; Machida, K.; Yamamoto, Y. Organometallics 2007, 26, 4697.(h) Bizet, V.; Cahard, D. Chimia. 2014, 68, 378.(i) Carrell, H. L.; Glusker, J. P.; Piercy, E. A.; Stallings, W. C.; Zacharias, D. E.; Davis, R. L.; Astbury, C.; Kennard, C. H. L. J. Am. Chem. Soc. 1987, 109, 8067.
15. [15]
  Nakamura, K.; Ohmori, K.; Suzuki, K. Angew. Chem., Int. Ed.2017, 56, 182.
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