Citation: Baobao Yu, Zhu-Jun Yao. A gram-scale laboratory synthesis of Annonaceous acetogenin mimic AA005[J]. Chinese Chemical Letters, ;2021, 32(1): 408-412. doi: 10.1016/j.cclet.2020.06.007 shu

A gram-scale laboratory synthesis of Annonaceous acetogenin mimic AA005

Baobao Yu ,
Zhu-Jun Yao ^*,

State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

yaoz@nju.edu.cn

Received Date: 6 May 2020
Revised Date: 22 May 2020
Accepted Date: 3 June 2020
Available Online: 5 June 2020

Figures(5)

AA005 (1), a potent anticancer mimicking molecule of natural Annonaceous acetogenin, features a central C₂-symmetric triglycol moiety and three stereogenic centers. To support ongoing animal studies, a scalable 10-step synthesis of AA005 (1) has been studied, optimized and accomplished in this work, starting from commercially available economic materials ethylene glycol and (R)-epichlorohydrin. A regio- and stereo-controlled BF₃·Et₂O-promoted epoxide opening of (R)-epichlorohydrin with ethylene glycol was investigated, optimized and successfully applied to the scalable preparation of the crucial fragment 6a with C₂-symmetry. Further successive epoxide openings elaborated both two side chains and the whole skeleton with proper nucleophiles and electrophiles. Comparison and optimization of the reaction sequences finally led to completion of a new multi-gram synthesis of AA005 (1) with satisfactory enantiomeric and diastereomeric purity.
- AA005,
- Scalable synthesis,
- Annonaceous acetogenin mimic,
- Symmetry,
- Epoxide opening
1. [1]
  (a) A. Bermejo, B. Figadere, M.C. Zafra-Polo, et al., Nat. Prod. Rep. 22 (2005) 269-303;
  (b) T.S. Hu, Y.L. Wu, Z.J. Yao, Recent progress on the chemical synthesis of Annonaceous acetogenins and their structurally modified mimics, in: Y.L. Wu, Z.J. Yao (Eds.), Synthesis of Natural Products: A Scientific and Artistic Exploration, Science Press, Beijing, 2006, pp. 58-90;
  (c) J.L. McLaughlin, J. Nat. Prod. 71 (2008) 1311-1321;
  (d) S. Gajalakshmi, R. Divya, V. Divya-Deepika, et al., Int. J. Pharm. Sci. Rev. Res. 10 (2011) 24-29;
  (e) S.M. Agarwal, M.I. Khan, M. Mangal, Anticancer Agents Med. Chem. 16 (2016) 138-159.
2. [2]
  D. Cortes, B. Figadere, A. Cave, Phytochemistry 32 (1993) 1467-1473. doi: 10.1016/0031-9422(93)85161-J
3. [3]
  (a) S. Hoppen, U. Emde, T. Friedrich, et al., Angew. Chem. Int. Ed. 39 (2000) 2099-2102;
  (b) T. Gallardo, M.C. Zafra-Polo, J.R. Tormo, et al., J. Med. Chem. 43 (2000) 4793-4800;
  (c) S. Arndt, U. Emde, S. Bäurle, et al., Chem. Eur. J. 7 (2001) 993-1005;
  (d) N. Kojima, T. Tanaka, Molecules 14 (2009) 3621-3661;
  (e) T. Matsumoto, N. Kojima, A. Akatsuka, et al., Tetrahedron 73 (2017) 2359-2366.
4. [4]
  (a) B.B. Zeng, Y. Wu, Q. Yu, et al., Angew. Chem. Int. Ed. 39 (2000) 1934-1937;
  (b) S. Jiang, Z.H. Liu, G. Sheng, et al., J. Org. Chem. 67 (2002) 3404-3408;
  (c) B.B. Zeng, Y. Wu, S. Jiang, et al., Chem. Eur. J. 9 (2003) 282-290;
  (d) S. Jiang, Y. Li, X.G. Chen, et al., Angew. Chem. Int. Ed. 43 (2004) 329-334;
  (e) H.X. Liu, G.R. Huang, H.M. Zhang, et al., ChemBioChem 8 (2007) 172-177;
  (f) Q.C. Xiao, Y.Q. Liu, Y.T. Qiu, et al., J. Med. Chem. 54 (2011) 525-533;
  (g) B. Han, Y.X. Cao, Z.M. Li, et al., Acta Pharmacol. Sin. 40 (2019) 231-242.
5. [5]
  (a) J.D. White, T.C. Somers, G.N. Reddy, J. Org. Chem. 57 (1992) 4991-4998;
  (b) Z.J. Yao, Y.L. Wu, Tetrahedron Lett. 35 (1994) 157-160;
  (c) Z.J. Yao, Y.L. Wu, J. Org, Chem. 60 (1995) 1170-1176.
6. [6]
  (a) P. Duret, B. Figadere, R. Hocquemiller, A. Cave, Tetrahedron Lett. 38 (1997) 8849-8852;
  (b) Q. Yu, Y.K. Wu, Y.L. Wu, et al., Chirality 12 (2000) 127-129.
7. [7]
  (a) X.P. Gu, I. Ikeda, M. Okahara, Synthesis 16 (1985) 649-651;
  (b) Z.G. Tang, C.W. Zhang, Y.L. Yue, Huaxue Shiji 2 (1994) 107-109;
  (c) Q.G. Huang, Guangxi Chem. Ind. 3 (1996) 13-14;
  (d) Z.X. Liu, L. Wang, C.Y. Bao, et al., Biomacromolecules 12 (2011) 2389-2395.
8. [8]
  (a) D.J. Yue, Hubei Chem. Ind. 1 (1994) 19-21;
  (b) Y. Zhang, Y.S. Xu, S.J. Qiu, L. Yang, Chem. Ind. & Eng. 31 (2014) 31-36.
9. [9]
  (a) M. Tokunaga, J.F. Larrow, F. Kakiuchi, E.N. Jacobsen, Science 277 (1997) 936-938;
  (b) S.E. Schaus, B.D. Brandes, J.F. Larrow, et al., J. Am. Chem. Soc. 124 (2002) 1307-1315;
  (c) L.P.C. Nielsen, C.P. Stevenson, D.G. Blackmond, E. N. Jacobsen, J. Am. Chem. Soc. 126 (2004) 1360-1362.
10. [10]
  F.D. Liu, K.K. Guo, J.M. Yuan, High Perform. Polym. 26 (2014) 326-334. doi: 10.1177/0954008313514083
11. [11]
  (a) A. Furstner, M. Albert, J. Mlynarski, M. Matheu, E. DeClercq, J. Am. Chem. Soc. 125 (2003) 13132-13142;
  (b) R. Schmidt, M. Ostermeier, R. Schobert, J. Org. Chem. 82 (2017) 9126-9132.
12. [12]
  M. Yamaguchi, I. Hirao, Tetrahedron Lett. 24 (1983) 391-394. doi: 10.1016/S0040-4039(00)81416-1
13. [13]
  M.P. Groziak, A. Koohang, J. Org. Chem. 57 (1992) 940-944. doi: 10.1021/jo00029a027
14. [14]
  T. Durand, A. Guy, J.P. Vidal, J.C. Rossi, J. Org. Chem. 67 (2002) 3615-3624. doi: 10.1021/jo0109624
15. [15]
  (a) D.J. Hart, W.P. Hong, L.Y. Hsu, J. Org. Chem. 52 (1987) 4665-4673;
  (b) J.A. Marshall, M.Z. Chen, J. Org. Chem. 62 (1997) 5996-6000.
16. [16]
  (a) T.R. Hoye, Z.X. Ye, J. Am. Chem. Soc. 118 (1996) 1801-1802;
  (b) D.J. Dixon, S.V. Ley, D.J. Reynolds, Angew. Chem. Int. Ed. 39 (20003622-3626;
  (c) S. Takahashi, A. Kubota, T. Nakata, Angew. Chem. Int. Ed. 41 (2002) 4751-4754.
17. [17]
  J.K. Fu, H.J. Shen, Y.Y. Chang, et al., Chem. Eur. J. 20 (2014) 12881-12888. doi: 10.1002/chem.201403756
18. [18]
  (a) T. Vijai-Kumar-Reddy, B.L. A. Prabhavathi-Devi, R.B.N. Prasad, P. Sujitha, C. Ganesh-Kumar, Eur. J. Med. Chem. 67 (2013) 384-389;
  (b) Y.J. Chen, S. Jin, J. Xi, Z.J. Yao, Tetrahedron 70 (2014) 4921-4928.
1. [1]
  Yujie Wang , Haoran Wang , Yanni Liu , Manhua Peng , Hongwei Fan , Hong Meng . A comprehensive review on the scalable and sustainable synthesis of covalent organic frameworks. Chinese Chemical Letters, 2025, 36(8): 110189-. doi: 10.1016/j.cclet.2024.110189
2. [2]
  Liming Li , Yanchang Liu , Peng Kang , Donghui Feng , Yuguang Zhang , Hangxing Ren , Jianrong Zeng , He Zhu , Qiang Li , Xiaoya Cui . Scalable and rapid liquid synthesis of PtNi electrocatalyst for hydrogen evolution reaction. Chinese Chemical Letters, 2026, 37(2): 112022-. doi: 10.1016/j.cclet.2025.112022
3. [3]
  Yuanpeng Ye , Longfei Yao , Guofeng Liu . Engineering circularly polarized luminescence through symmetry manipulation in achiral tetraphenylpyrazine structures. Chinese Journal of Structural Chemistry, 2025, 44(2): 100460-100460. doi: 10.1016/j.cjsc.2024.100460
4. [4]
  Na Wang , Wang Luo , Huaiyi Shen , Huakai Li , Zejiang Xu , Zhiyuan Yue , Chao Shi , Hengyun Ye , Leping Miao . Crystal engineering regulation achieving inverse temperature symmetry breaking ferroelasticity in a cationic displacement type hybrid perovskite system. Chinese Chemical Letters, 2024, 35(5): 108696-. doi: 10.1016/j.cclet.2023.108696
5. [5]
  Feng Cui , Fangman Chen , Xiaochun Xie , Chenyang Guo , Kai Xiao , Ziping Wu , Yinglu Chen , Junna Lu , Feixia Ruan , Chuanxu Cheng , Chao Yang , Dan Shao . Scalable production of mesoporous titanium nanoparticles through sequential flash nanocomplexation. Chinese Chemical Letters, 2024, 35(4): 108681-. doi: 10.1016/j.cclet.2023.108681
6. [6]
  Yue Sun , Liming Yang , Yaohang Cheng , Guanghui An , Guangming Li . Pd(I)-catalyzed ring-opening arylation of cyclopropyl-α-aminoamides: Access to α-ketoamide peptidomimetics. Chinese Chemical Letters, 2024, 35(6): 109250-. doi: 10.1016/j.cclet.2023.109250
7. [7]
  Zhenzhen Zhao , Meichen Jiao , Jiejie Ling , Han Jiang , Yan Gao , Hao Xu , Hai-Qing Li , Jingang Jiang , Peng Wu , Le Xu . Toward the microporous zeolite family with tunable large-medium cage and pore opening. Chinese Journal of Structural Chemistry, 2024, 43(9): 100336-100336. doi: 10.1016/j.cjsc.2024.100336
8. [8]
  Rong-Nan Yi , Wei-Min He . Visible light/copper catalysis enabled radial type ring-opening of sulfonium salts. Chinese Chemical Letters, 2025, 36(4): 110787-. doi: 10.1016/j.cclet.2024.110787
9. [9]
  He Zhao , Baiyang Fan , Siwen Hu , Xingliang Liu , Bo Tang , Pengchong Xue . Guest-triggered gate-opening of flexible hydrogen-bonded framework for separation of styrene and ethylbenzene. Chinese Chemical Letters, 2025, 36(10): 111005-. doi: 10.1016/j.cclet.2025.111005
10. [10]
  Feng Zhao , Hongyu Ding , Ting Sun , Chao Shen , Zu-Li Wang , Wei Wei , Dong Yi . Visible-light-promoted multi-component carbene transfer reactions of diazo compounds via ring-opening of cyclic ethers. Chinese Chemical Letters, 2026, 37(2): 111834-. doi: 10.1016/j.cclet.2025.111834
11. [11]
  Junqi Su , Wenhao Liu , Jianjun Wang , Weifen Luo , Yangyang Ma , Leiyang Lv , Zhiping Li . Palladium-catalyzed ring-opening defluorinative cross-coupling of gem-difluorocyclopropanes with fluoromalonates or fluorobis(phenylsulfonyl)methane. Chinese Chemical Letters, 2026, 37(3): 111288-. doi: 10.1016/j.cclet.2025.111288
12. [12]
  Rong-Nan Yi , Jun Jiang , Wei-Min He . Pd/NHC-catalyzed ring-opening cross-coupling of gem-difluorocyclopropanes via a 3,3′-reductive elimination pathway. Chinese Chemical Letters, 2026, 37(4): 112163-. doi: 10.1016/j.cclet.2025.112163
13. [13]
  Zheng Li , Fangkun Li , Xijun Xu , Jun Zeng , Hangyu Zhang , Lei Xi , Yiwen Wu , Linwei Zhao , Jiahe Chen , Jun Liu , Yanping Huo , Shaomin Ji . A scalable approach to Na₄Fe₃(PO₄)₂P₂O₇@carbon/expanded graphite as cathode for ultralong-lifespan and low-temperature sodium-ion batteries. Chinese Chemical Letters, 2025, 36(10): 110390-. doi: 10.1016/j.cclet.2024.110390
14. [14]
  Qinghong Zhang , Qiao Zhao , Xiaodi Wu , Li Wang , Kairui Shen , Yuchen Hua , Cheng Gao , Yu Zhang , Mei Peng , Kai Zhao . Visible-light-induced ring-opening cross-coupling of cycloalcohols with vinylazaarenes and enones via β-C-C scission enabled by proton-coupled electron transfer. Chinese Chemical Letters, 2025, 36(2): 110167-. doi: 10.1016/j.cclet.2024.110167
15. [15]
  Peiyan Zhu , Yanyan Yang , Hui Li , Jinhua Wang , Shiqing Li . Rh(Ⅲ)‐Catalyzed sequential ring‐retentive/‐opening [4 + 2] annulations of 2H‐imidazoles towards full‐color emissive imidazo[5,1‐a]isoquinolinium salts and AIE‐active non‐symmetric 1,1′‐biisoquinolines. Chinese Chemical Letters, 2024, 35(10): 109533-. doi: 10.1016/j.cclet.2024.109533
16. [16]
  Huimin Luan , Qinming Wu , Jianping Wu , Xiangju Meng , Feng-Shou Xiao . Templates for the synthesis of zeolites. Chinese Journal of Structural Chemistry, 2024, 43(4): 100252-100252. doi: 10.1016/j.cjsc.2024.100252
17. [17]
  Hang Wang , Qi Wang , Chuan-De Wu . Continuous synthesis of ammonia. Chinese Journal of Structural Chemistry, 2025, 44(3): 100437-100437. doi: 10.1016/j.cjsc.2024.100437
18. [18]
  Zhaojun Liu , Zerui Mu , Chuanbo Gao . Alloy nanocrystals: Synthesis paradigms and implications. Chinese Journal of Structural Chemistry, 2023, 42(11): 100156-100156. doi: 10.1016/j.cjsc.2023.100156
19. [19]
  Zhenhao Wang , Yuliang Tang , Ruyu Li , Shuai Tian , Yu Tang , Dehai Li . Bioinspired synthesis of cochlearol B and ganocin A. Chinese Chemical Letters, 2024, 35(7): 109247-. doi: 10.1016/j.cclet.2023.109247
20. [20]
  Hui Jin , Qin Cai , Peiwen Liu , Yan Chen , Derong Wang , Weiping Zhu , Yufang Xu , Xuhong Qian . Multistep continuous flow synthesis of Erlotinib. Chinese Chemical Letters, 2024, 35(4): 108721-. doi: 10.1016/j.cclet.2023.108721

Get Citation

PDF

XML

Metrics

PDF Downloads(10)
Abstract views(2327)
HTML views(197)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142