Facile, Stereocontrolled Synthetic Route towards Bis-functionalised Pyrrolizidines

Published as part of the Special Topic Heterocycles as Catalysts, Ligands, and Targets

Abstract

A simple and convenient method for the synthesis of bis-functionalised pyrrolizidines starting from readily available N-Cbz-l-prolinal is described. This aldehyde was converted within two concise steps to the corresponding aminoepoxides, which were separately subjected to regioselective cyclisation induced by a reductive cleavage of the Cbz protecting group. The versatile and concise strategy holds great potential for practical application in the straightforward preparation of pyrrolizidine-based drugs and natural products.

Key words

alkaloids - heterocycles - diastereoselective synthesis - asymmetric epoxidation - cyclisation - tandem reaction

• References

• 1 Robertson J. Stevans K. Nat. Prod. Rep. 2014; 31: 1721
• 2 Woldemichael GM. Wink M. Biochem. Syst. Ecol. 2002; 30: 139
• 3 Herrmann M. Joppe H. Schmaus G. Phytochemistry 2002; 60: 399
• 4 Wang Y.-H. Wang J.-H. He H.-P. Zhou H. Wang X.-W. Li CS. Hao X.-J. J. Asian Nat. Prod. Res. 2008; 69: 1927
• 5 Widenfield H. Montes B. Tawil B. Contin A. Wynsma R. Pharmazie 2006; 61: 559
• 6 Kostova N. Chritov V. Cholakova M. Nikolova E. Evestieva L. J. Serb. Chem. Soc. 2006; 71: 1275
• 7 Bai Y. Benn M. Duke N. Gul W. Huang YY. Rüeger H. ARKIVOC 2006; (iii): 34
• 8 Usuki H. Toyoka M. Kanzaki H. Okuda T. Nitoda T. Bioorg. Med. Chem. 2009; 17: 7248
• 9 Lones L. Hollinshead J. Fleet GW. Thompson AL. Watkin DJ. Gal ZA. Jenkinson SF. Kato A. Nash RJ. Phytochem. Lett. 2010; 3: 133
• 10 Xie W.-D. Li X. Row KH. Bull. Korean Chem. Soc. 2010; 31: 2715
• 11 Rochais C. Dallemagne P. Rault S. Anti-Cancer Agents Med. Chem. 2009; 9: 369
• 12 Cardona F. Goti A. Parmeggiani C. Parenti P. Forcella M. Fusi P. Cipolla L. Roberts SM. Davies GJ. Gloster TM. Chem. Commun. 2010; 46: 2629
• 13 Lidell JR. Nat. Prod. Rep. 2001; 18: 441
• 14 Chakler MT. Hepatology 2003; 39: 437
• 15 Asano N. Kato A. Watson AA. Mini-Rev. Med. Chem. 2001; 1: 145
• 16 Aoyagi T. Manabe T. Oohta T. Kurihara T. Pang G.-L. Yuhara T. Tetrahedron 1996; 52: 869
• 17 Majik MS. Jyoti S. Tilve SG. Parameswaran PS. Synthesis 2007; 663
• 18 Arisawa M. Takahasi M. Takezawa E. Yamaguchi Y. Torisawa YA. Nakagawa M. Chem. Pharm. Bull. 2000; 48: 1593
• 19 Lysenko IL. Kulinkovich OG. Russ. J. Org. Chem. 2005; 41: 73
• 20 Knight JG. Ley SV. Tetrahedron Lett. 1991; 32: 7119
• 21 Ishibashi H. Uemura N. Nakatani H. Okazaki M. Sato T. Nakamura N. Ikeda M. J. Org. Chem. 1993; 58: 2360
• 22 Hassner A. Singh S. Sharma R. Maurya R. Tetrahedron 1993; 49: 2317
• 23 Mulzer J. Shanyoor M. Tetrahedron Lett. 1993; 34: 6545
• 24 Ito H. Ikeuchi Y. Taguchi T. Hanzawa Y. J. Am. Chem. Soc. 1994; 116: 5469
• 25 Taddei M. Thereau F. Mann A. Coz S. Heterocycles 1993; 36: 2073
• 26 Hernández K. Gómez A. Joglar J. Bujons J. Parella T. Clapéz P. Adv. Synth. Catal. 2017; 359: 2090
• 27 Izquierdo I. Plaza MT. Yánez V. Tetrahedron: Asymmetry 2005; 16: 3887
• 28 Gryko D. Chalko J. Jurczak J. Chirality 2003; 15: 514
• 29 Li G. Zhao G. J. Org. Chem. 2005; 70: 4272
• 30 Rauniyar M. Hall DG. Angew. Chem. Int. Ed. 2006; 45: 2426
• 31 Krasiński A. Jurczak J. Tetrahedron Lett. 2001; 42: 2019
• 32 Krasiński A. Gruza H. Jurczak J. Heterocycles 2001; 54: 581
• 33 CCDC 1844880 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.
• 34 Kiyooka S. Nakano M. Shiota F. Fujiyama R. J. Org. Chem. 1989; 54: 5409
• 35 Krasiński A. Jurczak J. Tetrahedron: Asymmetry 2002; 13: 2075