Advertisement

Chemical Papers

, Volume 72, Issue 1, pp 221–227 | Cite as

Synthesis of sulfone analog of oseltamivir precursor

  • Viera Poláčková
  • Robert Šándrik
  • Radovan ŠebestaEmail author
Original Paper
  • 134 Downloads

Abstract

We describe here the synthesis of a sulfone analog of an oseltamivir precursor. The synthesis comprises cyclization of two advanced building blocks via one-pot Michael addition and Horner–Wadsworth–Emmons reaction. The first building block was synthesized by an organocatalytic Michael addition of pentyloxyacetaldehyde to a nitroalkene. The second, alkenylsulfone, building block was prepared by oxidation followed by a Mannich type reaction. The cyclization was accomplished under microwave irradiation.

Keywords

Organocatalysis Oseltamivir analog Michael addition, cyclization 

Notes

Acknowledgements

This work was supported by the Slovak Research and Development Agency under the Contract No. APVV-0067-11. This publication is the result of the project implementation: 26240120001 supported by the Research & Development Operational Programme funded by the European Regional Development Fund.

References

  1. Bahrami K, Khodaei MM, Sheikh Arabi M (2010) TAPC-promoted oxidation of sulfides and deoxygenation of sulfoxides. J Org Chem 75:6208–6213. doi: 10.1021/jo1011784 CrossRefGoogle Scholar
  2. Federspiel M, Fischer R, Hennig M, Mair H-J, Oberhauser T, Rimmler G, Albiez T, Bruhin J, Estermann H, Gandert C, Göckel V, Götzö S, Hoffmann U, Huber G, Janatsch G, Lauper S, Röckel-Stäbler O, Trussardi R, Zwahlen AG (1999) Industrial synthesis of the key precursor in the synthesis of the anti-influenza drug oseltamivir phosphate (Ro 64–0796/002, GS-4104-02): ethyl (3R,4S,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1-ene-1-carboxylate. Org Process Res Dev 3:266–274. doi: 10.1021/op9900176 CrossRefGoogle Scholar
  3. Flitsch W, Lubisch W (1984) Zur Umsetzung von 2-Pyrrolcarbaldehyd mit heterosubstituierten Ethenen. Chem Ber 117:1424–1435. doi: 10.1002/cber.19841170413 CrossRefGoogle Scholar
  4. Hajzer V, Latika A, Durmis J, Šebesta R (2012) Enantioselective Michael addition of the 2-(1-ethylpropoxy)acetaldehyde to N-[(1Z)-2-nitroethenyl]acetamide—optimization of the key step in the organocatalytic oseltamivir synthesis. Helv Chim Acta 95:2421–2428. doi: 10.1002/hlca.201200527 CrossRefGoogle Scholar
  5. Hajzer V, Fišera R, Latika A, Durmis J, Kollár J, Frecer V, Tučekova Z, Miertuš S, Kostolanský F, Varečková E, Šebesta R (2017) Stereoisomers of oseltamivir—synthesis, in silico prediction and biological evaluation. Org Biomol Chem 15:1828–1841. doi: 10.1039/C6OB02673G CrossRefGoogle Scholar
  6. Hayashi Y, Ogasawara S (2016) Time economical total synthesis of (−)-oseltamivir. Org Lett 18:3426–3429. doi: 10.1021/acs.orglett.6b01595 CrossRefGoogle Scholar
  7. Huťka M, Poláčková V, Marák J, Kaniansky D, Šebesta R, Toma Š (2010) Enantioselective organocatalytic Michael additions of oxyacetaldehydes to nitroolefins. Eur J Org Chem. doi: 10.1002/ejoc.201001032 Google Scholar
  8. Ishikawa H, Suzuki T, Hayashi Y (2009) High-yielding synthesis of the anti-influenza neuramidase inhibitor (−)-oseltamivir by three one-pot operations. Angew Chem Int Ed 48:1304–1307CrossRefGoogle Scholar
  9. Ishikawa H, Suzuki T, Orita H, Uchimaru T, Hayashi Y (2010) High-yielding synthesis of the anti-influenza neuraminidase inhibitor (−)-oseltamivir by two “one-pot” sequences. Chem Eur J 16:12616–12626. doi: 10.1002/chem.201001108 CrossRefGoogle Scholar
  10. Laborda P, Wang S-Y, Voglmeir J (2016) Influenza neuraminidase inhibitors: synthetic approaches, derivatives and biological activity. Molecules 21:1513CrossRefGoogle Scholar
  11. Midura WH, Krysiak JA (2004) Phosphonates containing sulfur and selenium. Synthesis of vinylphosphonates bearing α-sulfenyl, α-selenenyl, α-sulfinyl and α-seleninyl moieties and studies on nucleophilic addition. Tetrahedron 60:12217–12229. doi: 10.1016/j.tet.2004.10.026 CrossRefGoogle Scholar
  12. Mikolajczyk M, Grzejszczak S, Chefczynska A, Zatorski A (1979) Organosulfur compounds. 23. Addition of elemental sulfur to phosphonate carbanions and its application for synthesis of alpha-phosphoryl organosulfur compounds. Synthesis of aromatic ketones. J Org Chem 44:2967–2972. doi: 10.1021/jo01331a003 CrossRefGoogle Scholar
  13. Mikolajczyk M, Grzejszczak S, Korbacz K (1981) Addition of elemental selenium to phosphonate carbanions—a key step in the synthesis of vinylphosphonates. A new synthetic approach to 1,4-dicarbonyl systems. Tetrahedron Lett 22:3097–3100. doi: 10.1016/S0040-4039(01)81837-2 CrossRefGoogle Scholar
  14. Minami T, Nishimura K, Hirao I, Suganuma H, Agawa T (1982) Reactions of vinylphosphonates. 2. Synthesis of functionalized dienes, trienes, and their analogs. Synthetic applications to regioselectively functionalized benzene derivatives. J Org Chem 47:2360–2363. doi: 10.1021/jo00133a025 CrossRefGoogle Scholar
  15. Mukaiyama T, Ishikawa H, Koshino H, Hayashi Y (2013) One-pot synthesis of (−)-oseltamivir and mechanistic insights into the organocatalyzed Michael reaction. Chem Eur J 19:17789–17800. doi: 10.1002/chem.201302371 CrossRefGoogle Scholar
  16. Ogasawara S, Hayashi Y (2017) Multistep continuous-flow synthesis of (−)-oseltamivir. Synthesis 49:424–428. doi: 10.1055/s-2016-0036-1588899 Google Scholar
  17. Rehák J, Huťka M, Latika A, Brath H, Almássy A, Hajzer V, Durmis J, Toma S, Šebesta R (2012) Thiol-free synthesis of oseltamivir and its analogues via organocatalytic Michael additions of oxyacetaldehydes to 2-acylaminonitroalkenes. Synthesis 44:2424–2430CrossRefGoogle Scholar
  18. Sartori A, Dell’Amico L, Battistini L, Curti C, Rivara S, Pala D, Kerry PS, Pelosi G, Casiraghi G, Rassu G, Zanardi F (2014) Synthesis, structure and inhibitory activity of a stereoisomer of oseltamivir carboxylate. Org Biomol Chem 12:1561–1569. doi: 10.1039/C3OB42069H CrossRefGoogle Scholar
  19. Shie J-J, Fang J-M, Wang S-Y, Tsai K-C, Cheng Y-SE, Yang A-S, Hsiao S-C, Su C-Y, Wong C-H (2007) Synthesis of tamiflu and its phosphonate congeners possessing potent anti-influenza activity. J Am Chem Soc 129:11892–11893. doi: 10.1021/ja073992i CrossRefGoogle Scholar
  20. Silva S, Maycock CD (2017) Formal enantioselective syntheses of oseltamivir and tamiphosphor. Org Chem Front 4:236–240. doi: 10.1039/C6QO00510A CrossRefGoogle Scholar
  21. Tisovský P, Peňaška T, Mečiarová M, Šebesta R (2015) Enantioselective Michael reaction of acetals with nitroalkenes: an improvement of the oseltamivir synthesis. ACS Sustain Chem Eng 3:3429–3434. doi: 10.1021/acssuschemeng.5b01172 CrossRefGoogle Scholar
  22. Vivier M, Rapp M, Galmier M-J, Jarrousse A-S, Miot-Noirault E, Leal F, Weber V, Métin J, Sauzière J, Chezal J-M, Madelmont J-C (2011) New aldehyde and vinylsulfone proteasome inhibitors for targeted melanoma therapy. Eur J Med Chem 46:5705–5710. doi: 10.1016/j.ejmech.2011.07.037 CrossRefGoogle Scholar
  23. Weng J, Li Y-B, Wang R-B, Lu G (2012) Organocatalytic Michael reaction of nitroenamine derivatives with aldehydes: short and efficient asymmetric synthesis of (−)-oseltamivir. ChemCatChem 4:1007–1012. doi: 10.1002/cctc.201200124 CrossRefGoogle Scholar
  24. Zhu S, Yu S, Wang Y, Ma D (2010) Organocatalytic Michael addition of aldehydes to protected 2-amino-1-nitroethenes: the practical syntheses of oseltamivir (tamiflu) and substituted 3-aminopyrrolidines. Angew Chem Int Ed 49:4656–4660CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2017

Authors and Affiliations

  1. 1.Department of Organic Chemistry, Faculty of Natural SciencesComenius University in BratislavaBratislavaSlovakia

Personalised recommendations