tetano
Editor, Senior Moderator
Angew Chem Int Ed Engl. 2014 Oct 14. doi: 10.1002/anie.201408138. [Epub ahead of print]
Organocatalytic and Scalable Synthesis of the Anti-Influenza Drugs Zanamivir, Laninamivir, and CS-8958.
Tian J1, Zhong J, Li Y, Ma D.
Author information
Abstract
Zanamivir, laninamivir, and CS-8958 are three neuraminidase inhibitors that have been clinically used to combat influenza. We report herein a novel organocatalytic route for preparing these agents. Only 13 steps are needed for the assembly of zanamivir and laninamivir from inexpensive D-araboascorbic acid by this synthetic route, which relies heavily on a thiourea-catalyzed enantioselective Michael addition of acetone to tert-butyl (2-nitrovinyl)carbamate and an anti-selective Henry reaction of the resulting Michael adduct with an aldehyde prepared from D-araboascorbic acid. The synthetic procedures are scalable, as evident from the preparation of more than 3.5 g of zanamivir.
? 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
KEYWORDS:
anti-influenza drugs; asymmetric catalysis; organocatalysis; scalable synthesis; total synthesis
PMID:
25314609
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25314609
Organocatalytic and Scalable Synthesis of the Anti-Influenza Drugs Zanamivir, Laninamivir, and CS-8958.
Tian J1, Zhong J, Li Y, Ma D.
Author information
Abstract
Zanamivir, laninamivir, and CS-8958 are three neuraminidase inhibitors that have been clinically used to combat influenza. We report herein a novel organocatalytic route for preparing these agents. Only 13 steps are needed for the assembly of zanamivir and laninamivir from inexpensive D-araboascorbic acid by this synthetic route, which relies heavily on a thiourea-catalyzed enantioselective Michael addition of acetone to tert-butyl (2-nitrovinyl)carbamate and an anti-selective Henry reaction of the resulting Michael adduct with an aldehyde prepared from D-araboascorbic acid. The synthetic procedures are scalable, as evident from the preparation of more than 3.5 g of zanamivir.
? 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
KEYWORDS:
anti-influenza drugs; asymmetric catalysis; organocatalysis; scalable synthesis; total synthesis
PMID:
25314609
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25314609