High-yielding synthesis of the anti-influenza neuraminidase inhibitor (-)-oseltamivir by two "one-pot" sequences.
The efficient asymmetric total synthesis of (-)-oseltamivir, an antiviral reagent, has been accomplished by using two "one-pot" reaction sequences, with excellent overall yield (60 %) and only one required purification by column chromatography. The first one-pot reaction sequence consists of a diphenylprolinol silyl ether mediated asymmetric Michael reaction, a domino Michael reaction/Horner-Wadsworth-Emmons reaction combined with retro-aldol/Horner-Wadsworth-Emmons reaction and retro Michael reactions, a thiol Michael reaction, and a base-catalyzed isomerization. Six reactions can be successfully conducted in the second one-pot reaction sequence; these are deprotection of a tert-butyl ester and its conversion into an acyl chloride then an acyl azide, Curtius rearrangement, amide formation, reduction of a nitro group into an amine, and a retro Michael reaction of a thiol moiety. A column-free synthesis of (-)-oseltamivir has also been established.
Ishikawa
Hayato
H
Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Suzuki
Takaki
T
Orita
Hideo
H
Uchimaru
Tadafumi
T
Hayashi
Yujiro
Y
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004987:Ethers / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry; D013237:Stereoisomerism
D000998:Antiviral Agents; D004987:Ethers; C529940:diphenylprolinol silyl ether; D053139:Oseltamivir; D011392:Proline; D009439:Neuraminidase