中文
Announcement
More
Progress in Chemistry 2018, Vol. 30 Issue (5): 578-585 DOI: 10.7536/PC171131 Previous Articles   Next Articles

• Review •

Total Synthesis of the Akuammiline Alkaloid Strictamine

Xiaoyu Liu1, Tao Xiao2, Yong Qin1*   

  1. 1. West China School of Pharmacy, Sichuan University, Chengdu 610041, China;
    2. School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
  • Received: Revised: Online: Published:
  • Supported by:
    The work was supported by the National Natural Science Foundation of China (No. 21732005).
PDF ( 1054 ) Cited
Export

EndNote

Ris

BibTeX

Due to their complex and diverse structures and significant bioactivities, the chemical synthesis of the akuammiline alkaloids has been highly pursued in the chemical community. Strictamine, as one of the representative members in this natural product family, is structurally featured by a cage like methanoquinolizidine framework and an all-carbon quaternary stereogenic center at C7, posing a great challenge in synthesis. Pursuit in the total synthesis of strictamine has a history of over four decades; however, the breakthroughs came until the recent two years. This review briefly summarizes the three total syntheses and four formal syntheses of strictamine that have been reported since 2016, by highlighting the key strategies and reactions employed in each of the synthesis. Moreover, perspectives in this research field have also been suggested at the end of this review.
Contents
1 Introduction
2 Total synthesis and formal total synthesis of strictamine
2.1 Asymmetric total synthesis of (+)-strictamine by the Garg group
2.2 Total synthesis of (±)-strictamine by the Zhu group
2.3 Total synthesis of (±)-strictamine by the Zu group
2.4 Formal synthesis of (±)-strictamine by the Fujii/Ohno group
2.5 Formal synthesis of (+)-strictamine by the Snyder group
2.6 Formal synthesis of (±)-strictamine by the Gaich group
2.7 Formal synthesis of (+)-strictamine by the Qin group
3 Conclusion and outlook

CLC Number: 

[1] For selected reviews of akuammiline alkaloids, see:(a) Ramírez A, García-Rubio S. Curr. Med. Chem., 2003, 10:1891.;
(b) Adams G, Smith A B. The Alkaloids:Chemistry and Biology (Ed. Knolker H J). New York:Elsevier, 2016, 76:171.
[2] (a)李朝明(Li C M), 张宪民(Zhang X M), 周韵丽(Zhou Y L), 黄丽瑛(Huang L Y), 陶国达(Tao G D). 药学学报(Acta Pharm. Sin.), 1993, 28:512.;
(b)杜国顺(Du G S), 尚建华(Shang J H), 蔡祥海(Cai X H), 罗晓东(Luo X D). 云南植物研究(Acta Bot. Yunnanica), 2007, 29:366.
[3] Baliga M S,Meera S, Mathai B, Rai M P, Pawar V. Chin. J. Integr. Med., 2012, DOI:10.1007/s11655-011-0947-0.
[4] Henry T A, Sharp T M. J. Chem. Soc., 1927, 1950.
[5] Henry T A. J. Chem. Soc., 1932, 2759.
[6] Olivier L, Lévy J, Le Men J, Janot M M, Budzikiewicz H, Djerassi C. Bull. Soc. Chim. France, 1965, 868.
[7] For selected biological activity, see:(a) Dutta S C, Bhattacharya S K, Ray A B. Planta Med., 1976, 30:86.;
(b) Bhattacharya S K, Dutta S C, Ray A B, Guha S R. Indian J. Exp. Biol., 1979, 17:598.;
(c) Hugel G, Royer D, Men-Olivier L L, Richard B, Jacquier M J, Levy J. J. Org. Chem., 1997, 62:578.;
(d) Leewanich P, Tohda M, Matsumoto K, Subhadhirasakul S, Takayama H, Aimi N, Watanabe H. Eur. J. Pharmacol., 1997, 332:321.;
(e) Arai H, Hirasawa Y, Rahman A, Kusumawati I, Zaini N C, Sato S, Aoyama C, Takeo J, Morita H. Bioorg. Med. Chem., 2010, 18:2152.;
(f) Zaima K, Koga I, Iwasawa N, Hosoya T, Hirasawa Y, Kaneda T, Ismail I S, Lajis N H, Morita H. J. Nat. Med., 2013, 67:9.;
(g) Zhang L, Zhang C J, Zhang D B, Wen J, Zhao X W, Li Y, Gao K. Tetrahedron Lett., 2014, 55:1815.
[8] (a) Eckermann R, Gaich T. Synthesis, 2013, 2813.;
(b) Smith J M, Moreno J, Boal B W, Garg N K. Angew. Chem. Int. Ed., 2015, 54:400.
[9] Zhang M, Huang X P, Shen L Q, Qin Y. J. Am. Chem. Soc., 2009, 131:6013.
[10] (a) Zi W W, Zuo Z W, Ma D W. Acc. Chem. Res., 2015, 48:702.;
(b) Susick R B, Morrill L A, Picazo E, Garg N K. Synlett, 2017, 1.; During the preparation of this review, a related highlight article was published, see:
(c) Wang C, Zhang S J, Wang Y, Huang S H, Hong R. Org. Chem. Front., 2018, 5:447.
[11] Schnoes H K, Biemann K, Mokry J, Kompis I, Chatterjee A, Ganguli G. J. Org. Chem., 1966, 31:1641.
[12] Hou Y Y, Cao X L, Wang L Q, Cheng B F, Dong L Y, Luo X D, Bai G, Gao W Y. J. Chromatogr. B, 2012, 908:98.
[13] (a) Dolby L J, Esfandiari Z. J. Org. Chem., 1972, 37:43.;
(b) Dolby L J, Nelson S J. J. Org. Chem., 1973, 38:2882.
[14] (a) Moreno J, Picazo E, Morrill L A, Smith J M, Garg N K. J. Am. Chem. Soc., 2016, 138:1162.;
(b) Ren W W, Wang Q, Zhu J P. Angew. Chem. Int. Ed., 2016, 55:3500.;
(c) Xie X N, Wei B, Li G, Zu L S. Org. Lett., 2017, 19:5430.
[15] (a) Nishiyama D, Ohara A, Chiba H, Kumagai H, Oishi S, Fujii N, Ohno H. Org. Lett., 2016, 18:1670.;
(b) Smith M W, Zhou Z, Gao A X, Shimbayashi T, Snyder S A. Org. Lett., 2017, 19:1004.;
(c) Eckermann R, Breunig M, Gaich T. Chem. Commun., 2016, 52:11363.;
(d) Eckermann R, Breunig M, Gaich T. Chem. Eur. J., 2017, 23:3938.;
(e) Xiao T, Chen Z T, Deng L F, Zhang D, Liu X Y, Song H, Qin Y. Chem. Commun., 2017, 53:12665.
[16] (a) Lu Z Y, Li Y, Deng J, Li A. Nat. Chem., 2013, 5:679.;
(b) Xiong X C, Li Y, Lu Z Y, Wan M, Deng J, Wu S H, Shao H W, Li A. Chem. Commun., 2014, 50:5294.
[17] For the use of the Fischer indolization reaction in akuammiline alkaloid synthesis, see:(a) Zu L S, Boal B W, Garg N K. J. Am. Chem. Soc., 2011, 133:8877.;
(b) Smith J M, Moreno J, Boal B W, Garg N K. J. Am.Chem. Soc., 2014, 136:4504.;
(c) Smith J M, Moreno J, Boal B W, Garg N K. J. Org. Chem., 2015, 80:8954.
[18] For a review on catalytic asymmetric allylic alkylation employing heteroatom nucleophiles, see:Trost B M, Zhang T, Sieber J D. Chem. Sci., 2010, 1:427.
[19] (a) Solé D, Cancho Y, Llebaria A, Moréto J M, Delgado A. J. Am. Chem. Soc., 1994, 116:12133.;
(b) Bonjoch J, Solé D, García-Rubio S, Bosch J. J. Am. Chem. Soc., 1997, 119:7230.;
(c) Yu S, Mathias O, Cook J M. J. Am. Chem. Soc., 2000, 122:7827.;
(d) Yu F M, Cheng B, Zhai H B. Org. Lett., 2011, 13:5782.;
(e) Teng M X, Zi W W, Ma D W. Angew. Chem. Int. Ed., 2014, 53:1814.
[20] (a) Solé D, Bosch J, Bonjoch J. Tetrahedron, 1996, 52:4013.;
(b) Ren W W, Wang Q, Zhu J P. Angew. Chem. Int. Ed., 2014, 53:1818.
[21] (a) Yu Y Y, Li G, Jiang L, Zu L S. Angew. Chem. Int. Ed., 2015, 54:12627.;
(b) Yu Y Y, Li G, Zu L S. Synlett, 2016, 27:1303.;
(c) Li G, Xie X N, Zu L S. Angew. Chem. Int. Ed., 2016, 55:10483.
[22] Sole D, Cancho Y, Llebaria A, Moreto J M, Delgado A. J. Am. Chem. Soc., 1994, 116:12133.
[23] Hashmi A S K, Graf K, Ackermann M, Rominger F. ChemCatChem, 2013, 5:1200.
[24] For Cu-based precedent, see:(a) Fandrick D R, Fandrick K R, Reeves J T, Tan Z, Tang W, Capacci A G, Rodriguez S, Song J J, Lee H, Yee N K, Senanayake C H. J. Am. Chem. Soc., 2010, 132:7600.;
(b) Vieira E M, Haeffner F, Snapper M L, Hoveyda A H. Angew. Chem. Int. Ed., 2012, 51:6618.;
(c) Wei X F, Shimizu Y, Kanai M. ACS Cent. Sci., 2016, 2:21.
[25] For a Au-catalyzed process that requires silyl-indole protection, see:(a) Xu W Q, Wang W, Wang X. Angew. Chem. Int. Ed., 2015, 54:9546.; For related gold-catalyzed reactions, see:
(b) Liu Y X, Xu W Q, Wang X. Org. Lett., 2010, 12:1448.;
(c) Zhang L, Wang Y, Yao Z J, Wang S, Yu X Z. J. Am. Chem. Soc., 2015, 137:13290.
[26] Vanecko J A, Wan H, West F G. Tetrahedron, 2006, 62:1043.
[27] (a) Fang Y W, Li C Z. J. Org. Chem., 2006, 71:6427.;
(b) Wang Y, Kong C, Du Y, Song H, Zhang D, Qin Y. Org. Biomol. Chem., 2012, 10:2793.
[28] Qin W F, Xiao T, Zhang D, Deng L F, Wang Y, Qin Y. Chem. Commun., 2015, 51:16143.
[1] Xiaoxiao Wu, Kaiqing Ma. Total Synthesis of Stemona Alkaloids [J]. Progress in Chemistry, 2020, 32(6): 752-760.
[2] Luo Shipeng, Huang Peiqiang. Malic acid——A Versatile Chiral Building Block in the Enantioselective Total Synthesis of Natural Products and in Synthetic Methodologies [J]. Progress in Chemistry, 2020, 32(11): 1846-1868.
[3] Kangkang Zhi, Xin Yang. Natural Product Gels and Their Gelators [J]. Progress in Chemistry, 2019, 31(9): 1314-1328.
[4] Wu Li, Junjie Wang, Dawei Ma. The Total Synthesis of ent-Kaurane Diterpenoids [J]. Progress in Chemistry, 2019, 31(11): 1460-1471.
[5] Yuxia Gao, Yun Liang, Jun Hu, Yong Ju. Supramolecular Chiral Self-Assembly Based on Small Molecular Natural Products [J]. Progress in Chemistry, 2018, 30(6): 737-752.
[6] Tingting Huang, Zihua Zhou, Qi Liu, Xiaozheng Wang, Wenli Guo, Shuangjun Lin*. Biosynthetic Mechanisms of Alkaloids from Actinomycetes [J]. Progress in Chemistry, 2018, 30(5): 692-702.
[7] Xu Lining, Zhang Juntao, Tao Cheng, Cao Xiaoping. Advances in the Synthesis of Vinyl Chloride Compounds [J]. Progress in Chemistry, 2013, 25(11): 1876-1887.
[8] Wu Jindan, Ju Yong. Molecular and Ion Recognition Molecules Based on Natural Products [J]. Progress in Chemistry, 2013, 25(11): 1888-1897.
[9] Song Gao, Sumit Basu, Guangyi Yang, Arijita Deb, Ming Hu. Oral Bioavailability Challenges of Natural Products Used in Cancer Chemoprevention [J]. Progress in Chemistry, 2013, 25(09): 1553-1574.
[10] Tong Xing, Xiao Xiaohua, Deng Jianchao, Wang Jiayue, Li Gongke. Applications of Low Temperature Microwave Technique in Chemistry Research [J]. Progress in Chemistry, 2010, 22(12): 2462-2468.
[11] . The Study of Resource Chemistry [J]. Progress in Chemistry, 2010, 22(04): 537-556.
[12] Yang Zhen*. Syntheses of Biological Active Natural Products and Natural Product-Like Molecules [J]. Progress in Chemistry, 2009, 21(01): 47-54.
[13] Ge Huiming|Tan Renxiang**. Symbionts, an Important Source of New Bioactive Natural Products [J]. Progress in Chemistry, 2009, 21(01): 30-46.
[14]

Hu Jinfeng1,2**|Gary R.Eldridge1,Yu Yihua3,Mark O's Neil-Johnson2

. High-throughput Natural Product Chemistry Methods and the Application of the Capillary NMR Probe [J]. Progress in Chemistry, 2008, 20(04): 429-440.
[15] Zhenming Chen1, Jinhua Liu 2, Tao, Junhua2,3**. Biocatalysis for Green Chemistry and Drug Development [J]. Progress in Chemistry, 2007, 19(012): 1919-1927.