Formal Synthesis of (-)-Oseltamivir Phosphate
Abstract
The formal synthesis of (-)-oseltamivir phosphate (Tamiflu (TM)) was accomplished starting from (S)-pyroglutamic acid. The synthesis comprised two carbon-carbon bond forming reactions, the first one being a diastereoselective, indium-mediated allylation of a pyroglutamic aldehyde derivative. However, attempts to effect the second carbon-carbon bond formation - cyclohexene ring closure - using an enol-exo aldolization of a dialdehyde resulted in the formation of a product with the opposite regioselectivity. This shortcoming could be overcome by using a reaction sequence of Mannich methylenation/ring-closing metathesis, which provided the desired regioisomer in high yield.
Keywords:
antiviral agents / allylation / cyclization / metathesis / total synthesisSource:
Synthesis, Stuttgart, 2013, 45, 3, 389-395Publisher:
- Georg Thieme Verlag Kg, Stuttgart
Funding / projects:
- The development of new synthetic methods and their application in the synthesis of natural products and biologically active molecules (RS-MESTD-Basic Research (BR or ON)-172027)
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3495
DOI: 10.1055/s-0032-1317948
ISSN: 0039-7881
WoS: 000314632500018
Scopus: 2-s2.0-84872923889
Collections
Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Trajković, Milos AU - Ferjančić, Zorana AU - Saičić, Radomir PY - 2013 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1596 AB - The formal synthesis of (-)-oseltamivir phosphate (Tamiflu (TM)) was accomplished starting from (S)-pyroglutamic acid. The synthesis comprised two carbon-carbon bond forming reactions, the first one being a diastereoselective, indium-mediated allylation of a pyroglutamic aldehyde derivative. However, attempts to effect the second carbon-carbon bond formation - cyclohexene ring closure - using an enol-exo aldolization of a dialdehyde resulted in the formation of a product with the opposite regioselectivity. This shortcoming could be overcome by using a reaction sequence of Mannich methylenation/ring-closing metathesis, which provided the desired regioisomer in high yield. PB - Georg Thieme Verlag Kg, Stuttgart T2 - Synthesis, Stuttgart T1 - Formal Synthesis of (-)-Oseltamivir Phosphate VL - 45 IS - 3 SP - 389 EP - 395 DO - 10.1055/s-0032-1317948 ER -
@article{ author = "Trajković, Milos and Ferjančić, Zorana and Saičić, Radomir", year = "2013", abstract = "The formal synthesis of (-)-oseltamivir phosphate (Tamiflu (TM)) was accomplished starting from (S)-pyroglutamic acid. The synthesis comprised two carbon-carbon bond forming reactions, the first one being a diastereoselective, indium-mediated allylation of a pyroglutamic aldehyde derivative. However, attempts to effect the second carbon-carbon bond formation - cyclohexene ring closure - using an enol-exo aldolization of a dialdehyde resulted in the formation of a product with the opposite regioselectivity. This shortcoming could be overcome by using a reaction sequence of Mannich methylenation/ring-closing metathesis, which provided the desired regioisomer in high yield.", publisher = "Georg Thieme Verlag Kg, Stuttgart", journal = "Synthesis, Stuttgart", title = "Formal Synthesis of (-)-Oseltamivir Phosphate", volume = "45", number = "3", pages = "389-395", doi = "10.1055/s-0032-1317948" }
Trajković, M., Ferjančić, Z.,& Saičić, R.. (2013). Formal Synthesis of (-)-Oseltamivir Phosphate. in Synthesis, Stuttgart Georg Thieme Verlag Kg, Stuttgart., 45(3), 389-395. https://doi.org/10.1055/s-0032-1317948
Trajković M, Ferjančić Z, Saičić R. Formal Synthesis of (-)-Oseltamivir Phosphate. in Synthesis, Stuttgart. 2013;45(3):389-395. doi:10.1055/s-0032-1317948 .
Trajković, Milos, Ferjančić, Zorana, Saičić, Radomir, "Formal Synthesis of (-)-Oseltamivir Phosphate" in Synthesis, Stuttgart, 45, no. 3 (2013):389-395, https://doi.org/10.1055/s-0032-1317948 . .