Download PDF
Synlett 2013; 24(9): 1032-1043
DOI: 10.1055/s-0032-1316912
synpacts
© Georg Thieme Verlag Stuttgart · New York

Challenges and Strategies to the Total Syntheses of Fawcettimine-Type and Serratinine-Type Lycopodium Alkaloids

Xiaoming Wang
a   College of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P. R. of China
,
Houhua Li
b   National Institute of Biological Sciences (NIBS), Beijing 102206, P. R. of China   Fax: +86(10)80704785   Email: leixiaoguang@nibs.ac.cn
,
Xiaoguang Lei*
a   College of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P. R. of China
b   National Institute of Biological Sciences (NIBS), Beijing 102206, P. R. of China   Fax: +86(10)80704785   Email: leixiaoguang@nibs.ac.cn
› Author Affiliations
Further Information

Publication History

Received: 17 February 2013

Accepted after revision: 18 March 2013

Publication Date:
12 April 2013 (online)

   Buy Article Permissions and Reprints All articles of this category


Abstract

The fawcettimine- and serratinine-type lycopodium alkaloids are a series of structurally complex but related natural products. These alkaloids have been the subjects of intense studies by the synthetic chemistry community, and many elegant strategies have been developed. Herein, we describe the recently disclosed synthetic strategies towards this unique family of natural products, in particular the synthetic endeavors from our research laboratory.

Key words

total synthesis - fawcettimine - serratinine - lycopodium alkaloid - biosynthesis - collective synthesis - ring-chain tautomerism
 

  • References and Notes


      • For recent reviews of the lycopodium alkaloids, see:
    • 1a Ayer WA, Trifonov LS. The Alkaloids . Vol. 45. Cordell GA, Brossi A. Academic Press; New York: 1994: 233 ; and earlier reviews in this series
    • 1b Ma X, Gang DR. Nat. Prod. Rep. 2004; 21: 752
    • 1c Kobayashi J, Morita H In The Alkaloids . Vol. 61. Cordell GA. Academic Press; New York: 2005: 1
    • 1d Hirasawa Y, Kobayashi J, Morita H. Heterocycles 2009; 77: 679
    • 1e Kitajima M, Takayama H. Top. Curr. Chem. 2012; 309: 1
    • 1f Nakayama A, Kitajima M, Takayama H. Synlett 2012; 23: 2014

      For selected recent total syntheses of lycopodium alkaloids, see:
    • 2a Nilsson BL, Overman LE, Alaniz JR, Rohde JM. J. Am. Chem. Soc. 2008; 130: 11297
    • 2b Chandra A, Pigza JA, Han J.-S, Mutnick D, Johnston JN. J. Am. Chem. Soc. 2009; 131: 3470
    • 2c Yang H, Carter RG. J. Org. Chem. 2010; 75: 4929
    • 2d Laemmerhold KM, Breit B. Angew. Chem. Int. Ed. 2010; 49: 2367
    • 2e Tsukano C, Zhao L, Takemoto Y, Hirama M. Eur. J. Org. Chem. 2010; 4198
    • 2f Bisai V, Sarpong R. Org. Lett. 2010; 12: 2551
    • 2g Altman RA, Nilsson BL, Overman LE, Read de Alaniz J, Rohde JM, Taupin V. J. Org. Chem. 2010; 75: 7519
    • 2h Cheng X, Waters SP. Org. Lett. 2010; 12: 205
    • 2i Wolfe BH, Libby AH, Al-awar RS, Foti CJ, Comins DL. J. Org. Chem. 2010; 75: 8564
    • 2j Nakamura Y, Burke AM, Kotani S, Ziller JW, Rychnovsky SD. Org. Lett. 2010; 12: 72
    • 2k Liau BB, Shair MD. J. Am. Chem. Soc. 2010; 132: 9594
    • 2l Yuan C, Chang C.-T, Axelrod A, Siegel D. J. Am. Chem. Soc. 2010; 132: 5924
    • 2m Fischer DF, Sarpong R. J. Am. Chem. Soc. 2010; 132: 5926
    • 2n Nishimura T, Unni AK, Yokoshima S, Fukuyama T. J. Am. Chem. Soc. 2011; 133: 418
    • 2o Nakahara K, Hirano K, Maehata R, Kita Y, Fujioka H. Org. Lett. 2011; 13: 2015
    • 2p Barbe G, Fiset D, Charette AB. J. Org. Chem. 2011; 76: 5354
    • 2q Murphy RA, Sarpong R. Org. Lett. 2012; 14: 632
    • 2r Lin H, Causey R, Garcia GE, Snider BB. J. Org. Chem. 2012; 77: 7143
    • 2s Ge H, Zhang L, Tan R, Yao Z. J. Am. Chem. Soc. 2012; 134: 12323
    • 2t Shimada N, Abe Y, Yokoshima S, Fukuyama T. Angew. Chem. Int. Ed. 2012; 51: 11824

      For recent reports on the total synthesis of fawcettimine-type lycopodium alkaloids, see:
    • 3a Linghu X, Kennedy-Smith JJ, Toste FD. Angew. Chem. Int. Ed. 2007; 46: 7671
    • 3b Kozak JA, Dake GR. Angew. Chem. Int. Ed. 2008; 47: 4221
    • 3c Nakayama A, Kogure N, Kitajima M, Takayama H. Org. Lett. 2009; 11: 5554
    • 3d Ramharter J, Weinstabl H, Mulzer J. J. Am. Chem. Soc. 2010; 132: 14338
    • 3e Canham SM, France DJ, Overman LE. J. Am. Chem. Soc. 2010; 132: 7876
    • 3f Otsuka Y, Inagaki F, Mukai C. J. Org. Chem. 2010; 75: 3420
    • 3g Jung ME, Chang JJ. Org. Lett. 2010; 12: 2962
    • 3h Nakayama A, Kogure N, Kitajima M, Takayama H. Angew. Chem. Int. Ed. 2011; 50: 8025
    • 3i Yang Y.-R, Shen L, Huang J.-Z, Xu T, Wei K. J. Org. Chem. 2011; 76: 3684
    • 3j Zhang XM, Tu YQ, Zhang FM, Shao H, Meng X. Angew. Chem. Int. Ed. 2011; 50: 3916
    • 3k Li H, Wang X, Lei X. Angew. Chem. Int. Ed. 2012; 51: 491
    • 3l Pan G, Williams RM. J. Org. Chem. 2012; 77: 4801
    • 3m Canham SM, France DJ, Overman LE. J. Org. Chem. 2013; 78: 9
    • 3n Pan G, Williams RM. J. Org. Chem. 2012; 77: 4801
    • 3o Zhang X, Shao H, Tu Y, Zhang F, Wang S. J. Org. Chem. 2012; 77: 8174
    • 3p Li H, Wang X, Hong B, Lei X. J. Org. Chem. 2013; 78: 800

      • For early reports on the total synthesis of (±)-fawcettimine, see:
    • 3q Harayama T, Takatani M, Inubushi Y. Tetrahedron Lett. 1979; 4307
    • 3r Harayama T, Takatani M, Inubushi Y. Chem. Pharm. Bull. 1980; 28: 2394
    • 3s Heathcock CH, Smith KM, Blumenkopf TA. J. Am. Chem. Soc. 1986; 108: 5022
    • 3t Heathcock CH, Blumenkopf TA, Smith KM. J. Org. Chem. 1989; 54: 1548
    • 3u For other synthetic efforts toward (±)-fawcettidine, see: Boonsompat J, Padwa A. J. Org. Chem. 2011; 76: 2753
    • 3v For other synthetic efforts toward (–)-lycojapodine A, see: Yang Y, Shen L, Wei K, Zhao Q. J. Org. Chem. 2010; 75: 1317
  • 4 Burnell RH. J. Chem. Soc. 1959; 3091
  • 5 Burnell RH, Chin CG, Mootoo BS, Taylor DR. Can. J. Chem. 1963; 41: 3091
  • 6 Ayer WA, Fukazawa Y, Singer PP. Tetrahedron Lett. 1973; 5045
    • 7a Ayer WA, Altenkirk B, Valverde-Lopez S, Douglas B, Raffauf RF, Weisbach JA. Can. J. Chem. 1968; 46: 15
    • 7b Ayer WA, Altenkirk B, Fukazawa Y. Tetrahedron 1974; 4213
    • 7c Tan CH, Ma XQ, Chen GF, Jiang SH, Zhu DY. Chin. Chem. Lett. 2002; 13: 331
    • 7d Tan C, Ma X, Chen G, Zhu D. Can. J. Chem. 2003; 81: 315
  • 8 Hirasawa Y, Morita H, Shiro M, Kobayashi J. Org. Lett. 2003; 5: 3991
  • 9 He J, Chen X.-Q, Li M.-M, Zhao Y, Xu G, Cheng X, Peng L.-Y, Xie M.-J, Zheng Y.-T, Wang Y.-P, Zhao Q.-S. Org. Lett. 2009; 11: 1397
  • 11 Inubushi Y, Ishii H, Yasui B, Harayama Y, Hosokawa M, Nishino R, Nakahara Y. Yakugaku Zasshi 1967; 87: 1394

      • For total synthesis of 8-deoxyserratinine, see:
    • 12a Harayama T, Takatani M, Inubushi Y. Tetrahedron Lett. 1979; 4307
    • 12b Harayama T, Takatani M, Inubushi Y. Chem. Pharm. Bull. 1980; 28: 2394
    • 12c Yang Y.-R, Lai Z.-W, Shen L, Huang J.-Z, Wu X.-D, Yin J.-L, Wei K. Org. Lett. 2010; 12: 3430

      • For total synthesis of (±)-serratinine, see:
    • 12d Harayama T, Ohtani M, Oki M, Inubushi Y. J. Chem. Soc., Chem. Commun. 1974; 827
    • 12e Harayama T, Ohtani M, Oki M, Inubushi Y. Chem. Pharm. Bull. 1975; 23: 1511

      • For other synthetic efforts toward serratinine-type lycopodium alkaloids, see:
    • 12f Mehta G, Reddy MS, Radhakrishnan R, Manjula MV, Viswamitra MA. Tetrahedron Lett. 1991; 32: 6219
    • 12g Luedtke G, Livinghouse T. J. Chem. Soc., Perkin Trans. 1 1995; 2369
    • 12h Cassayre J, Gagosz F, Zard SZ. Angew. Chem. Int. Ed. 2002; 41: 1783

      • For total synthesis of other serratinine-type lycopodium alkaloids, see:
    • 12i Inubushi Y, Ishii H, Yasui B, Hashimoto M, Harayama T. Chem. Pharm. Bull. 1968; 16: 82
    • 12j Katakawa K, Kitajima M, Aimi N, Seki H, Yamaguchi K, Furihata K, Harayama T, Takayama H. J. Org. Chem. 2005; 70: 658
    • 13a Valters RE, Flitsch W. Ring-Chain Tautomerism . Katritzky AR. Plenum Press; New York: 1985

      • For selected excellent examples of ring-chain tautomerism manipulation in natural product synthesis, see:
    • 13b Chen X.-T, Gutteridge CE, Bhattacharya SK, Zhou B, Pettus TR. R, Hascall T, Danishefsky SJ. Angew. Chem. Int. Ed. 1998; 37: 185
    • 13c Marchais S, Al Mourabit A, Ahond A, Poupat C, Potier P. Tetrahedron Lett. 1999; 40: 5519
    • 13d Beye GE, Ward DE. J. Am. Chem. Soc. 2010; 132: 7210
    • 14a Inubushi Y, Ishii H, Yasui B, Harayama T. Tetrahedron Lett. 1966; 1551
    • 14b Ishii H, Yasui B, Harayama T, Inubushi Y. Tetrahedron Lett. 1966; 6215
    • 14c Inubushi Y, Ishii H, Harayama T. Tetrahedron Lett. 1967; 1069
  • 15 The dehydration of fawcettimine (1) to fawcettidine (2) was proposed and later realized by Inubushi et al. (see references 14b and 14c). The biogenetic hydration of 2 to 1 was also proposed by Gang and co-workers; see reference 1b.
  • 16 The biosynthetic approach was proposed by Kobayashi and co-workers (see reference 8). Tu et al. reported the biomimetic transformation of (±)-alopecuridine (4) into (±)-sieboldine A (5); see reference 3j.
  • 17 Ishii H, Yasui B, Nishino R.-I, Harayama T, Inubushi Y. Chem. Pharm. Bull. 1970; 18: 1880

      • For recent excellent reviews on SmI2-mediated reactions in total synthesis, see:
    • 18a Nicolaou KC, Ellery SP, Chen JS. Angew. Chem. Int. Ed. 2009; 48: 7140
    • 18b Szostak M, Procter DJ. Angew. Chem. Int. Ed. 2011; 50: 7737
  • 19 For an excellent review on hydroxyl-directed SmI2-mediated reductive couplings, see: Matsuda F. J. Synth. Org. Chem. Jpn. 1995; 53: 987

      • For the preparation of (5R)-5-methylcyclohex-2-enone (20), see:
    • 20a Fleming I, Maiti P, Ramarao C. Org. Biomol. Chem. 2003; 1: 3989
    • 20b Carlone A, Marigo M, North C, Landa A, Jørgensen KA. Chem. Commun. 2006; 4928
    • 21a Aldegunde MJ, Castedo L, Granja JR. Org. Lett. 2008; 10: 3789
    • 21b Mulzer and co-workers have reported a tandem allylsilane addition–aldol reaction sequence in their elegant total synthesis of lycoflexine, see reference 3d.
  • 22 O’Donnell CJ, Burke SD. J. Org. Chem. 1998; 63: 8614
    • 23a Murai A, Tanimoto N, Sakamoto N, Masamune T. J. Am. Chem. Soc. 1988; 110: 1985
    • 23b Murai A. Pure Appl. Chem. 1989; 61: 393
  • 24 For a similar axial-allyl group-directed intermolecular C-alkylation, see reference 3d.
    • 25a Kan T, Matsuda F, Yanagiya M, Shirahama H. Synlett 1991; 391
    • 25b Kito M, Sakai T, Yamada K, Matsuda F, Shirahama H. Synlett 1993; 158
    • 25c Kan T, Hosokawa S, Nara S, Oikawa M, Ito S, Matsuda F, Shirahama H. J. Org. Chem. 1994; 59: 5532
    • 25d Kawatsura M, Matsuda F, Shirahama H. J. Org. Chem. 1994; 59: 6900
    • 25e Kawatsura M, Hosaka K, Matsuda F, Shirahama H. Synlett 1995; 729
    • 25f Kawatsura M, Dekura F, Shirahama H, Matsuda F. Synlett 1996; 373
    • 25g Kito M, Sakai T, Haruta N, Shirahama H, Matsuda F. Synlett 1996; 1057
    • 25h Kawatsura M, Kishi E, Kito M, Sakai T, Shirahama H, Matsuda F. Synlett 1997; 479
    • 25i Matsuda F, Kawatsura M, Dekura F, Shirahama H. J. Chem. Soc., Perkin Trans. 1 1999; 2371
    • 25j Kan T, Nara S, Ozawa T, Shirahama H, Matsuda F. Angew. Chem. Int. Ed. 2000; 39: 355
    • 26a Otsubo K, Inanaga J, Yamaguchi M. Tetrahedron Lett. 1986; 27: 5763
    • 26b Inanaga J, Ishikawa M, Yamaguchi M. Chem. Lett. 1987; 1485
    • 26c Otsubo K, Kawamura K, Inanaga J, Yamaguchi M. Chem. Lett. 1987; 1487
    • 26d Otsubo K, Inanaga J, Yamaguchi M. Tetrahedron Lett. 1987; 28: 4437
  • 27 Yamashita D, Murata Y, Hikage N, Takao K, Nakazaki A, Kobayashi S. Angew. Chem. Int. Ed. 2009; 48: 1404
    • 28a Moorthy JN, Singhal H, Senapati K. Org. Biomol. Chem. 2007; 5: 767
    • 28b For an excellent review on IBX, see: Duschek A, Kirsch SF. Angew. Chem. Int. Ed. 2011; 50: 1524