Synthesis 2019; 51(09): 1980-1988
DOI: 10.1055/s-0037-1610687
paper
© Georg Thieme Verlag Stuttgart · New York

The Ambidextrous Pictet–Spengler Reaction: Access to the (+)- or (–)-Enantiomers of the Bioactive C-19 Methyl-Substituted Sarpagine/Macroline/Ajmaline Alkaloids from Either d- or l-Tryptophan

M. Toufiqur Rahman
,
James M. Cook*
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N. Cramer Street, Milwaukee, WI 53211, USA   Email: capncook@uwm.edu
› Author Affiliations
We gratefully acknowledge the NIH grants NS076517 and MH096463 for generous financial support.
Further Information

Publication History

Received: 10 November 2018

Accepted after revision: 18 December 2018

Publication Date:
18 February 2019 (eFirst)

Abstract

Depicted in the following is the proof of concept, which is important to illustrate the full potential of the ambidextrous Pictet–Spengler (P-S) reaction. Previously, both d-tryptophan and l-tryptophan were employed to synthesize the key intermediates toward the natural enantiomers of C-19 methyl-substituted alkaloids. Now the enantiomeric series of the same key intermediates could also be synthesized from both d- or l-tryptophan in high yield and optical purity via this P-S/Dieckmann protocol. One can make either the natural or the unnatural alkaloids from either of the chiral starting amino acid esters, stereo- and enantiospecifically for biological screening.

Supporting Information

 
  • References

  • 1 Dias DA, Urban S, Roessner U. Metabolites 2012; 2: 303
  • 2 Newman DJ, Cragg GM, Snader KM. Nat. Prod. Rep. 2000; 17: 215
  • 3 Koehn FE, Carter GT. Nat. Rev. Drug Discov. 2005; 4: 206
  • 4 Paterson I, Anderson EA. Science 2005; 310: 451
  • 5 Butler MS. Nat. Prod. Rep. 2008; 25: 475
  • 6 Newman DJ, Cragg GM. J. Nat. Prod. 2016; 79: 629
  • 7 Cragg GM, Newman DJ. Biochim. Biophys. Acta 2013; 1830: 3670
  • 8 O’Neil MJ. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals . Royal Society of Chemistry; London: 2013
  • 9 Feher M, Schmidt JM. J. Chem. Inf. Comput. Sci. 2003; 43: 218
  • 10 Liotta DC, Painter GR. Acc. Chem. Res. 2016; 49: 2091
  • 11 Wender PA, DeChristopher BA, Schrier AJ. J. Am. Chem. Soc. 2008; 130: 6658
  • 12 Carney DW, Lukesh JC, Brody DM, Brütsch MM, Boger DL. Proc. Natl. Acad. Sci. U.S.A. 2016; 113: 9691
  • 13 Lounasmaa M, Hanhinen P. In The Alkaloids: Chemistry and Biology, Vol. 55. Cordell GA. Academic Press; San Diego: 2001: 1-90
  • 14 Lounasmaa M, Hanhinen P, Westersund M, Halonen N. In The Alkaloids: Chemistry and Biology, Vol. 52. Cordell GA. Academic Press; San Diego: 1999: 103
  • 15 Namjoshi OA, Cook JM. In The Alkaloids: Chemistry and Biology, Vol. 76. Knölker H.-J. Academic Press; San Diego: 2016: 63
  • 16 Rahman MT, Cook JM. In Studies in Natural Products Chemistry, Vol. 64. Atta-ur-Rahman, Elsevier; Amsterdam: 2019. (in Press)
  • 17 Stöckigt J, Antonchick AP, Wu F, Waldmann H. Angew. Chem. Int. Ed. 2011; 50: 8538
  • 18 Klausen RS, Jacobsen EN. Org. Lett. 2009; 11: 887
  • 19 Raheem IT, Thiara PS, Peterson EA, Jacobsen EN. J. Am. Chem. Soc. 2007; 129: 13404
  • 20 Taylor MS, Jacobsen EN. J. Am. Chem. Soc. 2004; 126: 10558
  • 21 Cox ED, Cook JM. Chem. Rev. 1995; 95: 1797
  • 22 Herlé B, Wanner MJ, van Maarseveen JH, Hiemstra H. J. Org. Chem. 2011; 76: 8907
  • 23 Ruiz-Olalla A, Würdemann MA, Wanner MJ, Ingemann S, van Maarseveen JH, Hiemstra H. J. Org. Chem. 2015; 80: 5125
  • 24 Kayhan J, Wanner MJ, Ingemann S, van Maarseveen JH, Hiemstra H. Eur. J. Org. Chem. 2016; 3705
  • 25 Rahman MT, Tiruveedhula VV, Cook JM. Molecules 2016; 21: 1525
  • 26 Rahman MT, Cook JM. Eur. J. Org. Chem. 2018; 3224
  • 27 Rahman MT, Deschamps JR, Imler GH, Cook JM. Chem. Eur. J. 2018; 24: 2354
  • 28 Rahman MT, Deschamps JR, Imler GH, Schwabacher AW, Cook JM. Org. Lett. 2016; 18: 4174
  • 29 Edwankar RV, Edwankar CR, Deschamps J, Cook JM. Org. Lett. 2011; 13: 5216
  • 30 Edwankar RV, Edwankar CR, Deschamps JR, Cook JM. J. Org. Chem. 2014; 79: 10030
  • 31 Koskinen A, Lounasmaa M. In Progress in the Chemistry of Organic Natural Products, Vol. 43. Ingham JL. Springer; Vienna: 1983: 267
  • 32 Lounasmaa M, Hanhinen P, Westersund M. ChemInform 1999; 30
  • 33 Zeng J, Zhang D.-B, Zhou P.-P, Zhang Q.-L, Zhao L, Chen J.-J, Gao K. Org. Lett. 2017; 19: 3998
  • 34 Gao Y, Yu A.-L, Li G.-T, Hai P, Li Y, Liu J.-K, Wang F. Fitoterapia 2015; 107: 44
  • 35 Pan L, Terrazas C, Acuña UM, Ninh TN, Chai H, De Blanco EJ. C, Soejarto DD, Satoskar AR, Kinghorn AD. Phytochem. Lett. 2014; 10: 54
  • 36 Tan S.-J, Lim J.-L, Low Y.-Y, Sim K.-S, Lim S.-H, Kam T.-S. J. Nat. Prod. 2014; 77: 2068
  • 37 Zeng G.-y, Tian B.-h, Zhou R, Du L.-f, Xu C. Acta Pharmacol. Sin. 1991; 12: 471
  • 38 Cao P, Liang Y, Gao X, Li X.-M, Song Z.-Q, Liang G. Molecules 2012; 17: 13631
  • 39 Zhang L, Hua Z, Song Y, Feng C. Fitoterapia 2014; 97: 142
  • 40 Cheng G.-G, Zhao Y.-L, Zhang Y, Lunga P.-K, Hu D.-B, Li Y, Gu J, Song C.-W, Sun W.-B, Liu Y.-P. Tetrahedron 2014; 70: 8723
  • 41 Drinan MA, Lash TD. J. Heterocycl. Chem. 1994; 31: 255