Synthesis 2016; 48(06): 828-844
DOI: 10.1055/s-0035-1561289
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© Georg Thieme Verlag Stuttgart · New York

Quinolizidine-Based Alkaloids: A General Catalytic, Highly Enantio- and Diastereoselective Synthetic Approach

Chris Lindemann
Fakultät für Chemie und Mineralogie, Universität Leipzig, Institut für Organische Chemie, Johannisallee 29, 04103 Leipzig, Germany   Email: schneider@chemie.uni-leipzig.de
,
Christoph Schneider*
Fakultät für Chemie und Mineralogie, Universität Leipzig, Institut für Organische Chemie, Johannisallee 29, 04103 Leipzig, Germany   Email: schneider@chemie.uni-leipzig.de
› Author Affiliations
Further Information

Publication History

Received: 06 October 2015

Accepted after revision: 20 November 2015

Publication Date:
04 January 2016 (eFirst)

Abstract

Eleven quinolizidine-based alkaloids (QBAs) were synthesized in a straightforward, flexible, and stereoselective manner. As the key step, which was run on a multi-gram scale, the organocatalytic, highly enantio- and diastereoselective vinylogous Mukaiyama–Mannich reaction was used furnishing highly functionalized products carrying already two stereogenic centers. The quinolizidinone core was subsequently assembled through cyclization reactions of both ester groups with the amine moiety. Whereas the absolute configuration of the bridgehead carbon atom and the adjacent chiral center were established in the initial vinylogous Mannich reaction, the stereogenic center at the 4-position was introduced in the last step through amide activation and organometallic addition exploiting stereochemical control from the substrate. Taking advantage of this unified strategy, simple as well as more complex alkaloids were accessible in good overall yields and with high stereoselectivity. Some of the QBAs were synthesized for the first time and this study could help to assign their absolute and relative configurations.

Supporting Information

 
  • References

  • 1 Daly JW In Progress in the Chemistry of Organic Natural Products . Vol. 41. Herz W, Grisebach H, Kirby GW. Springer; Vienna: 1982: 205-340
    • 2a Daly JW, Brown GB, Mensah-Dwumah M, Myers CW. Toxicon 1978; 16: 163
    • 2b Daly JW. Toxin Rev. 1982; 1: 33
  • 3 Daly JW, Spande TF, Garraffo HM. J. Nat. Prod. 2005; 68: 1556
  • 4 Daly JW, Garraffo HM, Spande TF, Giddings L.-A, Saporito RA, Vieites DR, Vences M. J. Chem. Ecol. 2008; 34: 252
  • 5 Garraffo HM, Caceres J, Daly JW, Spande TF, Andriamaharavo NR, Andriantsiferana M. J. Nat. Prod. 1993; 56: 1016
  • 6 Daly JW. Proc. Natl. Acad. Sci. U.S.A. 1995; 92: 9
    • 7a Jones TH, Gorman JS. T, Snelling RR, Delabie JH. C, Blum MS, Garraffo HM, Jain P, Daly JW, Spande TF. J. Chem. Ecol. 1999; 25: 1179
    • 7b Saporito RA, Donnelly MA, Norton RA, Garraffo HM, Spande TF, Daly JW. Proc. Natl. Acad. Sci. U.S.A. 2007; 104: 8885
    • 7c Saporito RA, Norton RA, Andriamaharavo NR, Garraffo HM, Spande TF. J. Chem. Ecol. 2011; 37: 213
  • 8 Saporito RA, Donnelly MA, Madden AA, Garraffo HM, Spande TF. J. Nat. Prod. 2010; 73: 317
  • 9 Tsuneki H, You Y, Toyooka N, Kagawa S, Kobayashi S, Sasaoka T, Nemoto H, Kimura I, Dani JA. Mol. Pharmacol. 2004; 66: 1061
  • 10 Araya JA, Ramírez AE, Figueroa-Aroca D, Sotes GJ, Pérez C, Becerra J, Saez-Orellana F, Guzmán L, Aguayo LG, Fuentealba J. J. Alzheimers Dis. 2014; 42: 143
  • 12 Garraffo HM, Spande TF, Daly JW, Baldessari A, Gros EG. J. Nat. Prod. 1993; 56: 357
    • 13a Jain P, Garraffo HM, Yeh HJ, Spande TF, Daly JW, Andriamaharavo NR, Andriantsiferana M. J. Nat. Prod. 1996; 59: 1174
    • 13b Daly JW, Garraffo HM, Spande TF, Yeh HJ. C, Peltzer PM, Cacivio PM, Baldo JD, Faivovich J. Toxicon 2008; 52: 858
  • 14 Toyooka N, Kobayashi S, Zhou D, Tsuneki H, Wada T, Sakai H, Nemoto H, Sasaoka T, Garraffo HM, Spande TF, Daly JW. Bioorg. Med. Chem. Lett. 2007; 17. 5872
  • 15 Garraffo HM, Simon LD, Daly JW, Spande TF, Jones TH. Tetrahedron 1994; 50: 11329
    • 16a Michael JP. Nat. Prod. Rep. 1994; 11: 639
    • 16b Michael JP. Nat. Prod. Rep. 1995; 12: 535
    • 16c Michael JP. Nat. Prod. Rep. 1997; 14: 21
    • 16d Michael JP. Nat. Prod. Rep. 1997; 14: 619
    • 16e Michael JP. Nat. Prod. Rep. 1998; 15: 571
    • 16f Michael JP. Nat. Prod. Rep. 1999; 16: 675
    • 16g Michael JP. Nat. Prod. Rep. 2001; 18: 520
    • 16h Michael JP. Nat. Prod. Rep. 2002; 19: 719
    • 16i Michael JP. Nat. Prod. Rep. 2003; 20: 458
    • 16j Michael JP. Nat. Prod. Rep. 2004; 21: 625
    • 16k Michael JP. Nat. Prod. Rep. 2005; 22: 603
    • 16l Michael JP. Nat. Prod. Rep. 2007; 24: 191
    • 16m Michael JP. Beilstein J. Org. Chem. 2007; 3: 27
    • 16n Michael JP. Nat. Prod. Rep. 2008; 25: 139
    • 16o Michael JP In The Alkaloids . Vol. 75. Knölker H.-J. Elsevier Academic Press; London: 2016: 1
  • 17 Toyooka N, Tanaka K, Momose T, Daly JW, Garraffo H. Tetrahedron 1997; 53: 9553
  • 18 Toyooka N, Nemoto H. Tetrahedron Lett. 2003; 44: 569
    • 19a Pearson WH, Suga H. J. Org. Chem. 1998; 63: 9910
    • 19b Michel P, Rassat A. Chem. Commun. 1999; 2281
    • 19c Michel P, Rassat A, Daly JW, Spande TF. J. Org. Chem. 2000; 65: 8908
    • 19d Tsukano C, Oimura A, Enkhtaivan I, Takemoto Y. Org. Lett. 2012; 14: 1902
  • 20 Maloney KM, Danheiser RL. Org. Lett. 2005; 7: 3115
    • 21a Kinderman SS, de Gelder R, van Maarseveen JH, Schoemaker HE, Hiemstra H, Rutjes FP. J. T. J. Am. Chem. Soc. 2004; 126: 4100
    • 21b Mancey NC, Sandon N, Auvinet A.-L, Butlin RJ, Czechtizky W, Harrity JP. A. Chem. Commun. 2011; 47: 9804
    • 21c Amat M, Semak V, Escolano C, Molins E, Bosch J. Org. Biomol. Chem. 2012; 10: 6866
  • 22 Fellah M, Santarem M, Lhommet G, Mouriès-Mansuy V. J. Org. Chem. 2010; 75: 7803
  • 23 Michael JP, Accone C, de Koning CB, van der Westhuyzen CW. Beilstein J. Org. Chem. 2008; 4: 5
  • 24 Wong H, Garnier-Amblard EC, Liebeskind LS. J. Am. Chem. Soc. 2011; 133: 7517
  • 25 Huang H, Spande TF, Panek JS. J. Am. Chem. Soc. 2003; 125: 626
    • 26a Airiau E, Girard N, Pizzeti M, Salvadori J, Taddei M, Mann A. J. Org. Chem. 2010; 75: 8670
    • 26b Chou S.-SP, Huang J.-L. Molecules 2013; 18: 8243
    • 26c Chou S.-SP, Zhang J.-W, Chen K.-H. Tetrahedron 2013; 69: 1499
  • 27 Wang X, Li J, Saporito RA, Toyooka N. Tetrahedron 2013; 69: 10311
  • 28 Abels F, Lindemann C, Koch E, Schneider C. Org. Lett. 2012; 14: 5972
  • 29 Abels F, Lindemann C, Schneider C. Chem. Eur. J. 2014; 20: 1964
    • 30a Schneider C, Sickert M In Chiral Amine Synthesis . Nugent T. Wiley-VCH; Weinheim: 2010: 157
    • 30b Giera DS, Sickert M, Schneider C. Org. Lett. 2008; 10: 4259
  • 31 Sickert M, Schneider C. Angew. Chem. Int. Ed. 2008; 47: 3631
  • 32 Sickert M, Abels F, Lang M, Sieler J, Birkemeyer C, Schneider C. Chem. Eur. J. 2010; 16: 2806
  • 33 Abels F, Schneider C. Synthesis 2011; 4050
    • 34a Terada M. Chem. Commun. 2008; 4097
    • 34b Uraguchi D, Terada M. J. Am. Chem. Soc. 2004; 126: 5356
  • 35 Verkade JM. M, van Hemert LJ. C, Quaedflieg PJ. L. M, Alsters PL, van Delft FL, Rutjes FP. J. T. Tetrahedron Lett. 2006; 47: 8109
  • 36 Guazzelli G, Duffy LA, Procter DJ. Org. Lett. 2008; 10: 4291
  • 37 Pedregal C, Ezquerra J, Escribano A, Carreño M, García Ruano JL. Tetrahedron Lett. 1994; 35: 2053
  • 38 Aurell C.-J, Karlsson S, Pontén F, Andersen SM. Org. Process Res. Dev. 2014; 18: 1116
  • 39 Bertrand MB, Neukom JD, Wolfe JP. J. Org. Chem. 2008; 73: 8851
  • 40 Pinho VD, Burtoloso AC. Tetrahedron Lett. 2012; 53: 876
  • 41 Amat M, Semak V, Escolano C, Molins E, Bosch J. Org. Biomol. Chem. 2012; 10: 6866
  • 42 Xiao K.-J, Wang Y, Ye K.-Y, Huang P.-Q. Chem. Eur. J. 2010; 16: 12792
  • 43 Deslongchamps P. Stereoelectronic Effects in Organic Chemistry . Pergamon Press; Oxford: 1983
  • 44 Adams LL, Luzzio FA. J. Org. Chem. 1989; 54: 5387
    • 45a Ichikawa Y, Nishimura T, Hayashi T. Organometallics 2011; 30: 2342
    • 45b Peixoto PA, Richard J.-A, Severin R, Chen DY.-K. Org. Lett. 2011; 13: 5724
  • 46 CCDC 1414248 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.