Synthesis 2015; 47(18): 2819-2825
DOI: 10.1055/s-0034-1380430
special topic
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Total Synthesis of Tylophorine through a Formal [2+2] Cycloaddition Followed by Migrative Ring Opening of a Cyclobutane

Yousuke Yamaoka*
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan   Email: yyamaoka@pharm.kyoto-u.ac.jp   Email: kay-t@pharm.kyoto-u.ac.jp
,
Marie Taniguchi
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan   Email: yyamaoka@pharm.kyoto-u.ac.jp   Email: kay-t@pharm.kyoto-u.ac.jp
,
Ken-ichi Yamada
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan   Email: yyamaoka@pharm.kyoto-u.ac.jp   Email: kay-t@pharm.kyoto-u.ac.jp
,
Kiyosei Takasu*
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan   Email: yyamaoka@pharm.kyoto-u.ac.jp   Email: kay-t@pharm.kyoto-u.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 28 April 2015

Accepted after revision: 12 May 2015

Publication Date:
01 July 2015 (online)


Abstract

The asymmetric total synthesis of phenanthroindolizidine alkaloid (–)-tylophorine was achieved by asymmetric transfer hydrogenation of a cyclic imine. The cyclic imine with a pendant phenanthrene core was synthesized by a TfOH-promoted domino ring-contraction/ring-opening sequence of a cyclobutanol bearing an azide group, which was constructed by a formal [2+2] cycloaddition of a 2′-vinyl-1,1′-biaryl-2-yl ketone enolate. Catalytic asymmetric hydrogenation of the cyclic imine intermediate allowed the late-stage construction of the asymmetric center.

Supporting Information

 
  • References


    • For reviews of phenanthroindolizidine and phenanthroquinolizidine alkaloids, see:
    • 1a Li Z, Jin Z, Huang R. Synthesis 2001; 2365
    • 1b Chemler SR. Curr. Bioact. Compd. 2009; 5: 2
    • 1c Burtoloso AC. B, Bertonha AF, Rosset IG. Curr. Top. Med. Chem. 2014; 14: 191
  • 2 Ratnagiriswaran AN, Venkatachalam K. Indian J. Med. Res. 1935; 22: 433
    • 3a Gopalakrishnan C, Shankaranarayanan D, Kameswaran L, Natarajan S. Indian J. Med. Res. 1979; 69: 513
    • 3b Gopalakrishnan C, Shankaranarayanan D, Nazimudeen SK, Kameswaran L. Indian J. Med. Res. 1980; 71: 940
    • 3c Yang C.-W, Chen W.-L, Wu P.-L, Tseng H.-Y, Lee S.-J. Mol. Pharmacol. 2006; 69: 749
    • 3d Yang CW, Chuang T.-H, Wu P.-L, Huang W.-H, Lee S.-J. Biochem. Biophys. Res. Commun. 2007; 354: 942
    • 3e Wen T, Wang Z, Meng X, Wu M, Li Y, Wu X, Zhao L, Wang P, Yin Z, Li-Ling J, Wang Q. ACS Med. Chem. Lett. 2014; 5: 1027
  • 4 Wang K, Su B, Wang Z, Wu M, Li Z, Hu Y, Fan Z, Mi N, Wang Q. J. Agric. Food Chem. 2010; 58: 2703
  • 5 Donaldson GR, Atkinson MR, Murray AW. Biochem. Biophys. Res. Commun. 1968; 31: 104
  • 6 Wu C.-M, Yang C.-W, Lee Y.-Z, Chuang T.-H, Wu P.-L, Chao Y.-S, Lee S.-J. Biochem. Biophys. Res. Commun. 2009; 386: 140
  • 7 Stoye A, Peez TE, Opatz T. J. Nat. Prod. 2013; 76: 275
    • 8a Staerk D, Christensen J, Lemmich E, Duus JØ, Olsen CE, Jaroszewski JW. J. Nat. Prod. 2000; 63: 1584
    • 8b Gao W, Lam W, Zhong S, Kaczmarek C, Baker DC, Cheng Y.-C. Cancer Res. 2004; 64: 678
    • 9a Kim S, Lee T, Lee E, Lee J, Fan G.-J, Lee SK, Kim D. J. Org. Chem. 2004; 69: 3144
    • 9b Yang X, Shi Q, Bastow KF, Lee K.-H. Org. Lett. 2010; 12: 1416
    • 9c Stoye A, Opatz T. Org. Lett. 2010; 12: 2140
    • 9d Niphakis MJ, Georg GI. Org. Lett. 2011; 13: 196
    • 9e Lin Y.-D, Cho C.-L, Ko C.-W, Pulte A, Wu Y.-T. J. Org. Chem. 2012; 77: 9979
    • 9f Lin Q.-X, Ho T.-L. Tetrahedron 2013; 69: 2996
    • 10a Ihara M, Takino Y, Fukumoto K. Tetrahedron Lett. 1988; 29: 4135
    • 10b Ihara M, Takino Y, Tomotake M, Fukumoto K. J. Chem. Soc., Perkin Trans. 1 1990; 2287
    • 10c Comins DL, Salvador JM. J. Org. Chem. 1993; 58: 4656
    • 10d Suzuki H, Aoyagi S, Kibayashi C. J. Org. Chem. 1995; 60: 6114
    • 10e Comins DL, Chen X, Morgan LA. J. Org. Chem. 1997; 62: 7435
    • 10f Su B, Chen F, Wang Q. J. Org. Chem. 2013; 78: 2775
    • 10g Anton-Torrecillas C, Gonzalez-Gomez JC. Org. Biomol. Chem. 2014; 12: 7018
    • 10h Zheng Y, Liu Y, Wang Q. J. Org. Chem. 2014; 79: 3348
    • 10i Chen F, Su B, Wang Q. Org. Chem. Front. 2014; 1: 674
    • 11a Kim S, Lee J, Lee T, Park H.-G, Kim D. Org. Lett. 2003; 5: 2703
    • 11b Chemler SR, Zeng W. J. Org. Chem. 2008; 73: 6045
    • 11c Mai DN, Wolfe JP. J. Am. Chem. Soc. 2010; 132: 12157
    • 11d Cui M, Song H, Feng A, Wang Z, Wang Q. J. Org. Chem. 2010; 75: 7018
    • 11e Pansare SV, Lingampally R, Dyapa R. Eur. J. Org. Chem. 2011; 2235
    • 11f Su B, Zhang H, Deng M, Wang Q. Org. Biomol. Chem. 2014; 12: 3616
    • 12a Nagamoto Y, Yamaoka Y, Fujimura S, Takemoto Y, Takasu K. Org. Lett. 2014; 16: 1008
    • 12b Takasu K, Nagamoto Y, Takemoto Y. Chem. Eur. J. 2010; 16: 8427
    • 12c Nagamoto Y, Takemoto Y, Takasu K. Synlett 2013; 24: 120
    • 12d Nagamoto Y, Hattori A, Kakeya H, Takemoto Y, Takasu K. Chem. Commun. 2013; 49: 2622
  • 13 Nordlander JE, Njoroge FG. J. Org. Chem. 1987; 52: 1627
  • 14 Uematsu N, Fujii A, Hashiguchi S, Ikariya T, Noyori R. J. Am. Chem. Soc. 1996; 118: 4916
  • 15 Pearson WH, Fang W.-K. J. Org. Chem. 2000; 65: 7158
  • 16 Wendt JA, Aubé J. Tetrahedron Lett. 1996; 37: 1531 ; and references therein
  • 17 Williams GD, Pike RA, Wade CE, Wills M. Org. Lett. 2003; 5: 4227
  • 18 Cartigny D, Püntener K, Ayad T, Scalone M, Ratvelomanana-Vidal V. Org. Lett. 2010; 12: 3788
  • 19 Arican D, Brückner R. Org. Lett. 2013; 15: 2582