Synthesis of 4-azido-4-deoxy-Neu5,7,8,9Ac42en1Me. A key intermediate for the synthesis of GG167 from D-glucono-delta-lactone.
[reaction: see text] Stereoselective synthesis of 5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid methyl ester, an advanced key intermediate for the synthesis of neuraminidase inhibitor GG167 (Zanamivir, Relenza), was accomplished using D-glucono-delta-lactone as starting material. A highly diastereoselective allyllation of an imine intermediate, a regioselective azide-opening of an aziridine, and chemoselective oxidations of vicinal diols served successfully as key steps.
Liu
Ke-Gang
KG
State Key Laboratory of Bioorganic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Yan
Shi
S
Wu
Yu-Lin
YL
Yao
Zhu-Jun
ZJ
D000998:Antiviral Agents / Q000138:chemical synthesis*; D001386:Azides / Q000138:chemical synthesis*; D001388:Aziridines / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D005942:Gluconates / Q000737:chemistry; D006146:Guanidines; D007097:Imines / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D009438:Neuraminic Acids / Q000138:chemical synthesis*; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D011714:Pyrans; D012794:Sialic Acids / Q000138:chemical synthesis*; D019810:Sodium Azide; D013237:Stereoisomerism; D053243:Zanamivir
C500184:4-azido-4-deoxy-Neu5,7,8,9Ac42en1Me; D000998:Antiviral Agents; D001386:Azides; D001388:Aziridines; D004791:Enzyme Inhibitors; D005942:Gluconates; D006146:Guanidines; D007097:Imines; D007783:Lactones; D009438:Neuraminic Acids; D011714:Pyrans; D012794:Sialic Acids; D019810:Sodium Azide; D009439:Neuraminidase; C106477:glucono-1,4-lactone; D053243:Zanamivir