Synlett 2018; 29(05): 613-616
DOI: 10.1055/s-0036-1591880
letter
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Luteoalbusin A and Formal Synthesis of T988 C

Lushun Wang
Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   Email: yet@pkusz.edu.cn
,
Xuelei Jia
Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   Email: yet@pkusz.edu.cn
,
Honghui Lei
Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   Email: yet@pkusz.edu.cn
,
Zhengshuang Xu*
Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   Email: yet@pkusz.edu.cn
,
Tao Ye  *
Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   Email: yet@pkusz.edu.cn
› Author Affiliations
We acknowledge financial support from Shenzhen Peacock Plan (KQTD2015071714043444); NSFC (21772009, 21272011, 21572007), SZSTDF (JCYJ20140419131807793, JCYJ20130329175740481, JCYJ20160527100424909, ZDSYS201504301539161) and GDNSF (2014A030312004, 2014B030301003).
Further Information

Publication History

Received: 14 October 2017

Accepted after revision: 06 December 2017

Publication Date:
19 January 2018 (eFirst)

Abstract

An efficient total synthesis of luteoalbusin A was achieved in nine linear steps and in 17% overall yield from the known and easily accessible 3a-(3-indolyl)-hexahydropyrrolo[2,3-b]indole. A formal synthesis of (+)-T988 C through manipulation of the key intermediate is also reported.

Supporting Information

 
  • References

  • 1 Wang FZ. Huang Z. Shi XF. Chen YC. Zhang WM. Tian XP. Li J. Zhang S. Bioorg. Med. Chem. Lett. 2012; 22: 7265
  • 2 Feng Y. Blunt JW. Cole AL. J. Munro MH. G. J. Nat. Prod. 2004; 67: 2090
  • 3 Usami Y. Yamaguchi J. Numata A. Heterocycles 2004; 63: 1123
  • 4 Zheng C.-J. Kim C.-J. Bae KS. Kim Y.-H. Kim W.-G. J. Nat. Prod. 2006; 69: 1816
  • 5 Dong J.-Y. He H.-P. Shen Y.-M. Zhang K.-Q. J. Nat. Prod. 2005; 68: 1510
  • 6 Takahashi C. Numata A. Ito Y. Matsumura E. Araki H. Iwaki H. Kushida K. J. Chem. Soc., Perkin Trans. 1 1994; 1859
  • 7 Dong JY. Zhou W. Li L. Li GH. Liu YJ. Zhang KQ. Chin. Chem. Lett. 2006; 17: 922
  • 8 Overman LE. Shin Y. Org. Lett. 2007; 9: 339
  • 9 DeLorbe JE. Jabri SY. Mennen SM. Overman LE. Zhang F.-L. J. Am. Chem. Soc. 2011; 133: 6549
  • 10 Song J. Guo C. Adele A. Yin H. Gong L.-Z. Chem. Eur. J. 2013; 19: 3319
  • 11 Song L. Guo Q. Li X. Tian J. Peng Y. Angew. Chem. Int. Ed. 2012; 51: 1899
  • 12 Trost BM. Xie J. Sieber JD. J. Am. Chem. Soc. 2011; 133: 20611
  • 13 Sun M. Hao X. Liu S. Hao X. Tetrahedron Lett. 2013; 54: 692
  • 14 Xing D. Jing C. Li X. Qiu H. Hu W. Org. Lett. 2013; 15: 3578
  • 15 Arai T. Yamamoto Y. Awata A. Kamiya K. Ishibashi M. Arai MA. Angew. Chem. Int. Ed. 2013; 52: 2486
  • 16 Liu R. Zhang J. Org. Lett. 2013; 15: 2266
  • 17 Crich D. Fredette E. Flosi WJ. Heterocycles 1998; 48: 545
  • 18 Furst L. Narayanam JM. R. Stephenson CR. J. Angew. Chem. Int. Ed. 2011; 50: 9655
  • 19 Boyer N. Movassaghi M. Chem. Sci. 2012; 3: 1798
  • 20 Lei H. Wang L. Xu Z. Ye T. Org. Lett. 2017; 19: 5134
    • 21a Guo Y.-a. Zhao M. Xu Z. Ye T. Chem. Eur. J. 2017; 23: 3572
    • 21b Liao L. Zhou J. Xu Z. Ye T. Angew. Chem. Int. Ed. 2016; 55: 13263
    • 21c Zhou J. Gao B. Xu Z. Ye T. J. Am. Chem. Soc. 2016; 138: 6948
    • 21d Lei H. Yan J. Yu J. Liu Y. Wang Z. Xu Z. Ye T. Angew. Chem. Int. Ed. 2014; 53: 6533
  • 22 Adams TC. Payette JN. Cheah JH. Movassaghi M. Org. Lett. 2015; 17: 4268
    • 23a Iwasa E. Hamashima Y. Fujishiro S. Higuchi E. Ito A. Yoshida M. Sodeoka M. J. Am. Chem. Soc. 2010; 132: 4078
    • 23b Iwasa E. Hamashima Y. Fujishiro S. Hashizume D. Sodeoka M. Tetrahedron 2011; 67: 6587
  • 24 DeLorbe JE. Horne D. Jove R. Mennen SM. Nam S. Zhang F.-L. Overman LE. J. Am. Chem. Soc. 2013; 135: 4117
    • 25a Sano D. Nagata K. Itoh T. Org. Lett. 2008; 10: 1593
    • 25b Codelli JA. Puchlopek AL. A. Reisman SE. J. Am. Chem. Soc. 2012; 134: 1930
  • 26 Synthesis of luteoalbusin A (1): Hydrogen sulfide (ca. 2 mL) was condensed in a sealed tube (immersed in a Dewar at –78 °C) capped with a rubber septum. After a solution of 4 (9 mg, 14 μmol) in CH2Cl2 (2 mL) and BF3·OEt2 (18 μL, 0.14 mmol) were sequentially added by using syringes, the rubber septum was replaced with a sealed-tube stopper. The reaction vessel was slowly warmed to ambient temperature and stirred for 2 h. The reaction mixture was cooled to –78 °C again, and the sealed-tube stopper was changed to a rubber septum. The reaction vessel was connected by double-ended syringes to two tandem traps, which was filled with aqueous sodium hydroxide (100 mL, 20%). The cooling bath was removed, and the reaction solution was slowly warmed to room temperature. When gas evolution ceased, argon was used to purge for 0.5 h. Then the residue was dissolved in ethyl acetate (10 mL) and washed with a saturated aqueous solution of NH4Cl (5 mL). The aqueous layer was back-extracted with ethyl acetate (2 × 5 mL). The combined organic layers were stirred at room temperature, a solution of I2 (7 mg, 28 µmol) in ethyl acetate (1 mL) was added by using a syringe. The mixture was stirred for 2 min, and the reaction was quenched with sodium thiosulfate (5 mL, 10% aqueous solution). Layers were separated, and the aqueous phase was further extracted with ethyl acetate (2 × 10 mL). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by flash chromato­graphy on silica gel (eluent: gradient, 25% ethyl acetate in hexane) to afford luteoalbusin A (1; 3.6 mg, 55%) as a white foam. TLC: Rf = 0.45 (50% ethyl acetate in hexane); [α]D 20 = 312.9 (c 0.5, acetone); 1H NMR (500 MHz, acetone-d 6): δ = 10.24 (br. s, 1 H), 7.57 (d, J = 8.2 Hz, 1 H), 7.43 (d, J = 8.1 Hz, 1 H), 7.34 (d, J = 7.5 Hz, 1 H), 7.15 (d, J = 2.3 Hz, 1 H), 7.12 (dd, J = 8.0, 7.5 Hz, 1 H), 7.12 (dd, J = 7.9, 7.4 Hz, 1 H), 7.00 (dd, J = 8.0, 7.5 Hz, 1 H), 6.78 (d, J = 8.1 Hz, 1 H), 6.77 (dd, J = 8.0, 7.5 Hz, 1 H), 6.21 (br. s, 1 H), 5.99 (s, 1 H), 4.42 (d, J = 12.6 Hz, 1 H), 4.35 (d, J = 12.7 Hz, 1 H), 4.06 (d, J = 15.2 Hz, 1 H), 3.18 (s, 3 H), 3.10 (d, J = 15.3 Hz, 1 H). 13C NMR (125 MHz, acetone-d 6): δ = 168.1, 164.4, 150.7, 139.6, 134.5, 130.6, 127.1, 125.9, 124.8, 123.7, 121.1, 121.1, 120.8, 118.4, 113.8, 111.6, 85.1, 79.1, 76.1, 61.8, 57.6, 45.7, 28.7. HRMS: m/z [M + Na]+ calcd. for C23H20N4NaO3S2 +: 487.0869; found: 487.0870.
  • 27 Synthesis of 11: To a solution of compound 5 (16.0 mg, 0.026 mmol) and DTBMP (213 mg, 1.0 mmol) in acetonitrile (3 mL) at ambient temperature, trifluoroacetic anhydride (75 μL, 0.52 mmol) was added. After being stirred at room temperature for 14 h, the reaction mixture was diluted with ethyl acetate (50 mL). The organic solution was washed with an aqueous solution of NaHSO4 (1 N, 2 × 10 mL), water (2 × 10 mL) and brine (20 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (eluent: 15% ethyl acetate in hexanes) to afford 11 (13 mg, 86%) as a colorless oil. TLC: Rf = 0.81 (50% ethyl acetate in hexane); [α]D 20 = –6.0 (c 1.0, CHCl3); 1H NMR (500 MHz, acetone-d 6): δ = 8.18 (d, J = 8.4 Hz, 1 H), 7.89 (d, J = 8.1 Hz, 1 H), 7.52 (s, 1 H), 7.41–7.31 (m, 3 H), 7.23 (d, J = 7.9 Hz, 1 H), 7.17–7.07 (m, 2 H), 6.91 (s, 1 H), 6.73 (s, 1 H), 5.72 (d, J = 1.1 Hz, 1 H), 5.06 (d, J = 1.2 Hz, 1 H), 3.24 (s, 3 H), 1.66 (s, 9 H), 1.55 (s, 9 H). 13C NMR (125 MHz, acetone-d 6): δ = 155.4, 154.9, 152.7, 150.2, 143.0, 139.7, 137.2, 135.1, 134.6, 129.8, 129.0, 125.8, 125.4, 125.2, 125.0, 123.7, 121.1, 120.7, 120.2, 118.3, 116.5, 102.3, 85.1, 84.9, 82.8, 58.4, 29.8, 28.3, 28.3. HRMS: m/z [M + Na]+ calcd. for C33H34N4O6Na+: 605.2371; found: 605.2371.